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9th Conference on Retroviruses and Opportunistic InfectionsSeattle, Washington - February 24 -February 28, 2002 |
Cite as: Conf Retroviruses Opportunistic Infect. 2002 Feb 24-28;9th:Abstract No. xx
Plenary Lectures |
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| L1 | SIV Reservoirs and Human Zoonotic Risk. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. L1 Hahn B. To assess this risk, my group has begun to characterize the prevalence, geographic distribution, and genetic diversity of naturally occurring SIV infections, investigated to what extent humans are exposed to SIV through hunting and handling of primate bushmeat, developed non-invasive methods of SIV detection in endangered primate species, and conducted the first prevalence study and molecular characterization of SIVcpz in wild-living chimpanzees. The implications of our findings for the origins of HIV-1 and SIVcpz, and for assessing human zoonotic risk, will be discussed. |
| L2 | Dendritic Cell Responses and Host Interactions Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. L2 Melissa Pope Clarifying these issues will define the exact role of DCs in the transmission and dissemination of HIV infection and disease progression. This will facilitate the development of methods to improve the immune-activating capacity of DCs that will advance vaccine and therapeutic approaches as well as the design of strategies to prevent DC-driven infection that may be incorporated in microbicide development. |
| L3 | Immune Reconstitution and Immunologic Responses to Antiretroviral Therapies: Implications for Therapeutic Strategies Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. L3 Brigitte Autran Such a phenomenon does not reflect definitive alterations of the immune responses to HIV but rather reflects the insufficient production of HIV antigens during HAART. Such an hypothesis is supported by the rapid rebounds of HIV-specific CD4 and CD8 T cells during virus relapses following treatment discontinuation. This latter strategy is only partially helpful in chronic infection since the rare virus-specific CD4 T cells rapidly disappear in the face of pathogenic virus particles while only preexisting CD8 clones specific for HIV reappear and the immune repertoire does not broaden. Alternative promising strategies are opened by the association of anti-HIV vaccines to HAART in order to restimulate HIV-specific immunity before treatment is stopped, protect the host, and prolong time off therapy. Several programs of therapeutic immunization are in progress using recombinant attenuated pox-viruses or other vaccines. |
| L4 | Analysis of HIV-1 Envelope Glycoproteins and Neutralizing Antibodies Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. L4 P. Kwong1,4, S. Majeed1,4, S.-H. Xiang2, R. Gupta2, L. Wang2, M. Doyle3, D. Casper3, W. Hendrickson1, J. Sodroski2 and R. Wyatt*2,4 The identification of conformationally-fixed glycoproteins may provide unique molecules useful for the design of gp120-based vaccines and may provide insights for gp120-directed drug development. |
| L5 | A Potential HIV-1 Vaccine Using a Replication-Defective Adenoviral Vaccine Vector. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. L5 Emilio Emini for the Merck HIV-1 Vaccine Research Team BACKGROUND: The importance of the host cellular immune response for control of HIV-1 infection in seropositive humans is well-established. Although a prophylactic vaccine to prevent HIV-1 infection should preferably elicit both antiviral cellular and humoral immune responses, an immunogen that consistently induces broa |
| L6 | New Insights into Mechanisms of HIV-1 Resistance to Reverse Transcriptase Inhibitors. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. L6 John Mellors Further insights into the mechanisms of resistance, cross-resistance, resistance reversal and hypersusceptibility will undoubtedly lead to the more rationale use and design of RT inhibitors. |
| L7 | Treatment of Patients with Drug Resistant Virus. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. L7 Ann Collier Individualizing the approach for patients with drug resistant virus will ensure therapy minimizes the downsides and maximizes the benefits. This difficult management dilemma challenges all HIV laboratory scientists, clinical researchers, treatment advocates, and care providers to continue the quest to improve therapy and access to therapy for all persons with HIV. |
| L8 | HIV-1 Virion Morphogenesis. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. L8 Hans-Georg Kraeusslich This issue is of particular importance for understanding PR-inhibitor resistance, which appears to involve a mixture of alterations conferring resistance and those restoring viral fitness. Furthermore, virus assembly and reorganisation may also provide attractive targets for novel antiretrovirals, since capsid stability is maintained by multiple, weak, non-covalent interactions. |
| L9 | Transmission and Propagation of SIV and HIV Infection in vivo. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. L9 Ashley Haase This presentation will focus on how access, substrate availability, and spatial proximity affect transmission and propagation of SIV and HIV infection in vivo. A description of the first in rhesus macaque SIV model of heterosexual transmission, the role of preexisting inflammation in creating a "leaky" mucosal barrier, the different roles of resting and activated CD4+ T cells in transmission, virus production, and the dynamics of infection, based on evidence derived from new amplification technologies to visualize virus production. The presentation will conclude with a discussion of how virus-specific CD8, CTLs, and other factors profoundly alter levels of virus gene expression in vivo vis-a-vis infection of cell cultures. |
Oral Abstracts |
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| 1 | SCH C: Safety and Antiviral Effects of a CCR5 Receptor Antagonist in HIV-1- Infected Subjects Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 1 J. Reynes1, R. Rouzier2, T. Kanouni2, V. Baillat2, B. Baroudy3, A. Keung3, C. Hogan4, M. Markowitz4, and M. Laughlin3 Preliminary data with SCH C supports the CCR5 receptor as a viable target for antiretroviral therapy. |
| 2 | AMD-3100, a CXCR4 Antagonist, Reduced HIV Viral Load and X4 Virus Levels in Humans Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 2 Schols D1, S. Claes1, E. De Clercq1, C. Hendrix2, G. Bridger3, G. Calandra3, G. Henson3, S. Fransen4, W. Huang4, J. M. Whitcomb4, and C. J. Petropoulos4 for the AMD-3100 HIV study group 1 patient with pure X4 virus, receiving AMD-3100, exhibited a viral load reduction that was virologically and phenotypically consistent with an antiviral effect. Also in 8 patients with dual or mixed virus at baseline, X4 viruses were no longer detected at day 11 at a dose as low as 5 mcg/kg/h. The PhenoSense assay accurately determined the co-receptor tropism of HIV from patient samples and may be used to predict drug susceptibility and virologic response. |
| 3 | Determining the Relative Efficacy of Tenofovir DF Using Frequent Measurements of HIV-1 RNA During a Short Course of Monotherapy in Antiretroviral Drug Naive Individuals. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 3 M. Louie*1, C. Hogan1, A. Hurley1, B. Captan1, J. Flaherty2, P. Lamy2, A. Balagtas2, D. F. Coakley2, C. Chung1, D. Ho1, and M. Markowitz1 Based on determinations of relative efficacy, tenofovir DF has robust antiretroviral activity with potency comparable to ritonavir monotherapy. |
| 4 | TMC125, A Next-Generation NNRTI, Demonstrates High Potency After 7 Days Therapy in Treatment-Experienced HIV-1-Infected Individuals with Phenotypic NNRTI Resistance. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 4 B. Gazzard*1, A. Pozniak1, K. Arasteh2, S. Staszewski3, W. Rozenbaum4, P. Yeni5, G. van't Klooster6, K. De Dier6, M. Peeters6, M. P. de Béthune6, N. Graham7, and R. Pauwels6 TMC125, a next-generation NNRTI, administered at 900 mg BID for 7 days in treatment-experienced patients with highly NNRTI-resistant virus and currently failing on an NNRTI-containing regimen demonstrates significant antiviral potency and is well tolerated. |
| 5 | TMC125 Monotherapy for 1 Week Results in a Similar Initial Rate of Decline of HIV-1 RNA as Therapy with a 5-Drug Regimen Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 5 S. Sankatsing1, G. Weverling1, G. van't Klooster2, J. Prins1, and J. Lange*1 Monotherapy with the TMC125 in ART-naïve, HIV-1-infected individuals results in a similar initial rate of decline of plasma HIV-1 during the first week of therapy as a 5-drug regimen. These results demonstrate that TMC125 is a highly potent NNRTI. |
| 6 | Study DPC 083-203, a Phase II Comparison of 100 and 200 mg Once-Daily DPC 083 and 2 NRTIs in Patients Failing a NNRTI-Containing Regimen Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 6 N. Ruiz*1, R. Nusrat1, E. Lauenroth-Mai2, D. Berger3, C. Walworth4, L. T. Bacheler1, L. Ploughman1, P. Tsang1, D. Labriola1, R. Echols1, R. Levy1, and the DPC 083-203 Study Team Responses at week 8 suggest that DPC 083 is active in patients who have failed marketed NNRTIs and harbor NNRTI-resistant mutations. Response rates appear to be higher when DPC 083 is used in combination with at least 1 new NRTI. DPC 083 was generally well tolerated. |
| 7 | Study DPC 083-201: A Phase II Double-Blind (DB) Comparison of 3 Once Daily Doses of the NNRTI DPC 083 vs 600 mg Efavirenz (EFV) in Combination with 2 NRTIs in HIV Anti-Retroviral (ARV) Treatment-Naive Patients. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 7 N. Ruiz*1, R. Nusrat1, A. Lazzarin2, K. Arasteh3, F-D. Goebel4, S. Audagnotto5, A. Rachlis6, J. R. Arribas7, L. Ploughman1, W. Fiske1, D. Labriola1, R. Levy1, and R. Echols1 for the DPC 083-201 Study Team DPC 083 was highly effective and well tolerated in ARV-naïve patients. Compared with EFV, occurrence of dizziness was lower and of rash, dose-related. DPC 083 provides free trough plasma levels that exceed the IC90 for virus containing key NNRTI-resistant mutations. |
| 8 | S-1360: in Vitro Activity of a New HIV-1 Integrase Inhibitor in Clinical Development. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 8 T. Yoshinaga1, A. Sato1, T. Fujishita1, and T. Fujiwara*2 S-1360 represents a new class of potent anti-HIV agents. These results coupled with acceptable pre-clinical safety and animal PK profiles support the currently ongoing clinical investigations. |
| 9 | Identification and Characterization of a Novel Inhibitor of HIV-1 Entry - I: Virology and Resistance. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 9 P-F. Lin, B. Robinson, Y-F. Gong, K. Ricarrdi, Q. Guo, C. Deminie, R. Rose, T. Wang, N. Meanwell, Z. Yang, H. Wang, T. Zhang, and R. Colonno* The entry inhibitors described here are distinct from the CCR-5 and fusion inhibitors described by others. The encouraging preclinical profile of this novel inhibitor and its potential utility in all patient populations warrants further evaluation. |
| 10 | Identification and Characterization of a Novel Inhibitor of HIV-1 Entry - II: Mechanism of Action. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 10 P-F. Lin, K. Guo, R. Fridell, H-T. Ho, G. Yamanaka, and R. Colonno* Therefore, this novel class of HIV entry inhibitors block HIV-1 access into cells by binding to gp120 and inhibiting gp120/CD4 interactions. This novel class of entry inhibitors has the potential to expand current treatment options and address many of the needs for improved antiretroviral therapy. |
| 11 | HIV Prevalence in the United States, 2000 Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 11 P. L. Fleming*, R. H. Byers, P. A. Sweeney, D. Daniels, J. M. Karon, and R. S. Janssen HIV prevalence is likely to increase < 3% per year if current trends continue. The proportion of infected persons who know their status is increasing; three-quarters have been diagnosed, but a large proportion may not be in ongoing care. |
| 12 | HIV Infection among Men with Infectious Syphilis in Chicago, 1998-2000 Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 12 C. A . Ciesielski*1,2, and S. Boghani1 MSM with infectious syphilis were 1.6 times more likely to have been tested for HIV infection and 10 times more likely to be HIV+ than heterosexual men. The high proportion of HIV infection among these men is concerning, suggesting a high level of unsafe sexual activity among persons with known HIV infection. As about a third of these men have not been tested for HIV infection, these data also demonstrate that a significant proportion of very high-risk men are not being tested for HIV and highlight the critical need to increase HIV testing and educational efforts among both MSM and high-risk heterosexual men. |
| 13 | Lower Mortality in Ambulatory HIV-Infected Patients who Initiate Antiretroviral Therapy at Higher CD4+ Cell Counts Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 13 F. Palella*1, M. Knoll1, J. Chmiel1, A. Moorman2, K. Wood3, A. Greenberg2, and S. Holmberg2 for the HIV Outpatient Study (HOPS) Investigators These preliminary data suggest that initiation of ART for patients with CD4 201-350 cells/mm3, and possibly those with CD4 351-500, is associated with reduction in mortality in comparison with those for whom such therapy is delayed. Such survival benefits should be considered when evaluating the optimal timing of ART initiation. |
| 14 | Deaths from Non-AIDS-Related Diseases Have Increased as a Proportion of Deaths of HIV-Infected Persons since the Advent of HAART. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 14 M. I. Wolfe*, D. L. Hanson, R. Selik, and D. L. Swerdlow This study demonstrates that since the advent of HAART there have been declines in proportions of deaths from some AIDS-related causes, likely due to both improved treatment and prophylaxis. However, this study shows that there have been increasing proportions of some deaths from non-AIDS-related causes including liver and kidney disease, and possibly ischemic heart disease. While these results may be partially explained simply by the declines in AIDS-related causes, data from this analysis should be used to guide research into the question of whether some of these increases may be due to adverse outcomes from HAART or due to the aging population of persons infected with HIV. |
| 15 | Acceptability, Behavioral Impact, and Possible Efficacy of Post-Sexual-Exposure Chemoprophylaxis (PEP) for HIV Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 15 M. Schechter*1 , R. F. Lago1 , R. Ismerio1 , A. B. Mendelsohn2, and L. H. Harrison2 Although reported subjective side-effects were relatively common, > 90% of PEP courses were completed. The reported behaviors on average improved in this cohort with access to PEP. PEP failure occurred only once and it was associated with resistance to one of the antiretrovirals used. |
| 16 | Outbreak of HIV-1 and HCV Infection among Illegal Blood Donors in China Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 16 L. Zhang*1, Y. Cao2, J. Yu1, T. He1, W. Yu1, Z. Chen1, N. Yin2, S. Mei2, Z. Zhou2, Y. He2, W. Lu2, Z. Chen1, and D. Ho1 In conclusion, our findings show that the epidemics of HIV-1 and HCV infection in China are the consequences of multiple introductions. The distinct distribution patterns of HIV-1 and HCV genotypes in different high-risk groups are tightly linked to the mode of transmission rather than geographic proximity. Our findings should compel health care workers and government officials to implement necessary preventive measures to prevent the further dissemination of these viruses in the world's most populous nation. |
| 17 | Spreading of a Non-B Recombinant Form in Seroconverting IVDUs. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 17 S. Jost1, S. Yerly*1, D. Kaufmann2, M. Monnat2, A. Telenti2, J. P. Chave2, L. Kaiser1, P. Burgisser2, M. Flepp3, and L. Perrin1 Unlike the recombinant A/B epidemic in Leningrad IVDUs, the spread of the recently introduced recombinant J/A in IVDUs remains restricted to a relatively small area in Switzerland and almost exclusively in IVDUs. This study also indicates that, even in a small population, recombination events can be detected (A and B C2V3 within the context of a novel recombinant virus). |
| 18 | Tracking the Worldwide Subtype C Epidemic Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 18 C. Kuiken*, U. R. Smith, D. Lang, and T. Bhattacharya While in Africa the overall pattern in the subtype C epidemic appears to be chaotic, there are regions where distinct sub-epidemics can be identified. It is possible that patterns will emerge when the sampling density increases. The Asian epidemic is probably much younger (dating from the mid-1980s) and tracing the spread of the virus here appears to be very feasible. While the number of well-annotated sequences is small, increased awareness and interest in designing an appropriate vaccine should lead to a rapid accumulation of data. |
| 19 | Detection of Human Immunodeficiency Virus (HIV) Type 1 and Type 2 RNA and DNA in Vaginal Secretions among Women in Senegal, West Africa Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 19 C. W. Critchlow*1 , S. Hawes1, M. Redman1, P. Sow2, and N. Kiviat1 Frequency of detection and vaginal HIV RNA levels were higher among women with HIV-1 than HIV-2. Increased rates of vaginal HIV shedding, and most likely, of transmission, seen among women with HIV-1 appears to be attributable to higher viral burden at a given CD4 count among women with HIV-1. |
| 20 | Factors Associated with Clinical Progression in HIV-2-Infected Patients Included in the French ANRS Cohort Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 20 Matheron S, Pueyo S, Damond F, Campa P, Simon F, Chene G, Brun-Vezinet F, The French HIV-2 Cohort Study Group; Bichat-Claude Bernard Hosp., Paris BACKGROUND: Our purpose was to identify factors associated with clinical progression (new B or C event or death) in the French HIV-2 national cohort. METHODS: A prospective, multicenter cohort of adult HIV-2-infected patients was initiated in 1994. Epidemiological, clinical, biological, and therapeutic data were collec |
| 21 | Equal Plasma Viral Loads Predict a Similar Rate of CD4+ T-Cell Decline in Human Immunodeficiency Virus (HIV) Type-1 and HIV Type-2-Infected Individuals from Senegal, West Africa Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 21 Gottlieb GS, Sow P, Hawes S, Ndoye I, Redman M, Coll-Seck AM, Faye M, Diop A, Kuypers JM, Critchlow CW, Respess R, Mullins J, Kiviat N; Univ. of Washington, Seattle BACKGROUND: In comparison to HIV-1, HIV-2 infection is characterized by slower disease progression and lower rates of transmission. Gaining insights into the relationship between plasma HIV RNA viral load, PBMC HIV DNA levels, and the rate of CD4+ cell decline associated with HIV-2 as compared to HIV-1 infection is ess |
| 22 | Dynamics of T-Lymphocyte Turnover in Sooty Mangabeys, a Nonpathogenic Host of Simian Immunodeficiency Virus Infection Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 22 Kaur A, Barabasz AF, Rosenzweig M, McClure H, Feinberg MB, Johnson RP; New England Regional Primate Res. Ctr., Harvard Med. Sch., Southborough, MA BACKGROUND: Although several studies have demonstrated the presence of increased T- lymphocyte turnover in pathogenic HIV/SIV infection, there is little data in nonpathogenic lentiviral infection. Sooty mangabeys, a natural host of SIV, do not develop AIDS despite high viral loads and viral turnover rates that are comp |
| 23 | Down-Regulation of CCR5 on CD4+ T Cells of SIVsm-Infected Sooty Mangabeys. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 23 Veazey R, Ling B, Lackner A, Marx P; Tulane Regional Primate Res. Ctr., Covington, LA BACKGROUND: Sooty mangabey monkeys are the natural host species for simian immunodeficiency virus (SIVsm). Despite high levels of viral replication and persistence, sooty mangabeys infected with SIVsm do not develop AIDS, maintain relatively stable CD4+ T-cell counts, and live an apparently normal lifespan. In contrast |
| 24 | Blockade of T-Cell Co-Stimulation during Acute SIV Infection in Rhesus Macaques Blunts SIV-Specific Cellular Immune Responses but Does not Protect Them from AIDS Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 24 Garber D, Silvestri G, Fedanov A, Kozyr N, Barry A, Ibegbu C, Carter A, Anderson D, Wang X, Mittler R, McClure H, Larsen C, Altman J, Staprans S, Feinberg MB; Emory Vaccine Res. Ctr., Atlanta, GA BACKGROUND: SIV infection of rhesus macaques results in immune system activation and in progression to simian AIDS. In contrast, sooty mangabey monkeys, a natural reservoir of SIV, exhibit little immune activation or CTL responses to SIV, despite high levels of cytopathic viral replication. Further, sooty mangabeys do |
| 25 | Innate Immune Defense Mechanisms Involved in the Control of HIV Replication: Inverse Correlation of HIV Viremia with NK Cell Function. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 25 Kottilil S, Chun TW, Moir S, Liu S, McLaughlin M, Maldarelli F, Fauci AS; NIAID, NIH, Bethesda, MD BACKGROUND: CD8+ T-cell-mediated viral suppression has been described in HIV-infected individuals. However, the role of the innate immune system in the control of HIV replication is unclear. We examined both cell and soluble factor-mediated suppression of endogenous HIV replication in CD4+ T cells from infected individ |
| 26 | CD63: A Potential Co-Factor for HIV Infection of Macrophages. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 26 Von Lindern J, Grovit-Ferbas K, Yeramian C, Pappas TC, Deng C, Herbein G, Ferguson M, O'Brien WA; Univ. of Texas Med. Branch, Galveston BACKGROUND: Macrophages are important target cells for HIV infection and contribute to pathogenesis by serving as a long-lived viral reservoir. Culture or cytokine activated macrophages are more susceptible to HIV infection, as compared with monocytes. Identification of cellular factors that are involved in efficient H |
| 27 | Intestinal Mucosal Macrophages Are a Principle Reservoir of HIV Replication and Sustain High Levels of Infectious Virus in Persons with Chronic Progressive HIV Infection Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 27 Brodie S, Tabet S, Krieger J, Haggitt R, Nickle D, Johnson A, Coombs RW, Mullins J, Corey L, Celum C; Univ. of Washington, Seattle BACKGROUND: The gastrointestinal tract is both an early site of HIV infection and immune dysregulation, where mucosal leukocytes are the initial targets of virus replication. METHODS: We measured cell-associated HIV proviral DNA and replicative HIV RNA in rectal mucosal lymphocytes, macrophages (Mj), and dendritic cell |
| 28 | Expression of DC-SIGN by Intestinal and Genital Mucosal Dendritic Cells in Humans and Rhesus Macaques Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 28 Jameson B, Baribaud F, Pohlmann S, Ghavimi D, Mortari F, Doms R, Iwasaki A; Yale Univ., New Haven, CT BACKGROUND: Dendritic cells (DCs) are proposed to play a key role in HIV transmission and pathogenesis. To better understand the mechanism of HIV interaction with DCs at mucosal surfaces, we examined the expression of the HIV adhesion molecule, dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN), its closely |
| 29 | Apoptosis of Uninfected Bystander T Cells Induced by HIV-1 Viruses with Enhanced Affinity for CD4 and Increased Exposure of the Co-Receptor Binding Site Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 29 Holm G, Zhang C, Gabuzda D; Dana-Farber Cancer Inst., Boston, MA BACKGROUND: During HIV-1 infection, both infected and uninfected CD4+ T cells undergo apoptosis, contributing to T-cell depletion. We investigated the ability of HIV-1 to induce apoptosis in uninfected bystander CD4+ and CD8+ T cells, and determinants of the viral envelope that influence indirect cytopathic effects. |
| 30 | The CCR5 Promoter Polymorphism P1 is Associated with Enhanced Expression of HIV-1 Entry Co-Receptors CCR5, CXCR4, and CCR3 on Primary T Cells Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 30 Carrington M, Perfetto S, Lamoreaux L, Wang C, Larrimore K, Ehrenberg P, Michael N; NCI, NIH, Frederick, MD BACKGROUND: Subjects homozygous for haplotype P1 in the promoter region of CCR5, a major co-receptor for cellular entry of HIV-1, have previously been shown to progress more rapidly to AIDS. No association between cell surface expression of HIV entry co-receptors on primary CD4+ T cells and CCR5 promoter genotype has b |
| 31 | An Objective Case Definition of HIV Lipodystrophy Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 31 A. Carr* for the HIV Lipodystrophy Case Definition Study Group This model can diagnose HIV lipodystrophy objectively and relatively simply. |
| 32 | Switching Stavudine or Zidovudine to Abacavir for HIV Lipoatrophy: A Randomised, Controlled, Open-Label, Multicentre, 24-Week Study. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 32 A. Carr*1, D. Smith2, C. Workman3, J. Hoy4, N. Doong5, J. Amin2, M. Law2, D. A. Cooper1,2, and the MITOX Study Group LA in HIV-infected adults improves, but does not normalise, and viral load remains stable, after switching to ABC from d4T or AZT for 24 weeks. |
| 33 | Prospective Study of Hyperlipidemia in ART-Naive Subjects Taking Combivir/Abacavir (COM/ABC), COM/Nelfinavir (NFV), or Stavudine (d4T)/Lamivudine (3TC)/NFV (ESS40002). Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 33 P. Kumar*1, A. Rodriguez-French 2, M. Thompson3, K. Tashima4, V. Williams5, P. Wannamaker5, and M. Shaefer5 These 48-week results indicate that therapy with COM/ABC has comparable virologic and immunologic efficacy with a more favorable lipid profile as compared to PI-containing regimens. Gender differences will be presented. |
| 34 | Distinguishable Lipid Profiles between PI and NNRTI Therapy May Carry Different Risk of Cardiovascular Disease (CVD). Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 34 van Leth F, Friis-Moller N, Weber R, d'Arminio A, Kirk O, Thiebaut R, Morfeldt L, Pradier C, Calvo G, Law M, Bartsch G, De Wit S, Sabin C, Lundgren JD, Reiss P, The DAD Study Group; ATHENA, Amsterdam, The Netherlands BACKGROUND: PI-containing ART is associated with increased plasma total cholesterol (TC) and triglycerides (TG), without much change in HDL-cholesterol (HDL-c). In contrast, a rise in HDL-c leading to a reduced TC/HDL-c ratio has been shown in NNRTI-containing ART. We analysed lipid profiles in patients on different AR |
| 35 | Incidence of Symptomatic Hyperlactatemia in HIV-Infected Adults on NRTIs. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 35 Lonergan JT, Havlir D, Barber E, Mathews WC; Univ. of California, San Diego BACKGROUND: Symptomatic hyperlactatemia (SH) is associated with NRTI therapy and is characterized by abdominal complaints, liver abnormalities, and elevated lactate levels. The purpose of this study was to investigate whether the incidence rate (IR) of this complication varies with the number of NRTIs or with NRTI comb |
| 36 | Incidence of Grade IV Events, AIDS, and Mortality in a Large Multicenter Cohort Receiving HAART Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 36 Reisler R, Han C, Burman W, Tedaldi E, Neaton J; NIAID,NIH, Bethesda, MD BACKGROUND: Use of highly active antiretroviral therapy (HAART) for HIV has made a dramatic impact upon survival. Yet, there is a paucity of data regarding the incidence of life threatening events in the era of HAART. We therefore sought to quantify the incidence of grade IV events and mortality in a multicenter HIV co |
| 37 | Safe Interruption of Maintenance Therapy (MT) against Prior Infection with 4 Common HIV-Associated Opportunistic Pathogens during Highly Active Antiretroviral Therapy. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 37 Kirk O, Reiss P, Uberti-Foppa C, Bickel M, Gerstoft J, Pradier C, Wit F, Ledergerber B, Lundgren JD, Furrer H, 7 European HIV cohorts; EuroSIDA, Copenhagen, Denmark BACKGROUND: The safety of interrupting MT for cytomegalovirus end-organ disease ( CMV ), disseminated Mycobacterium avium complex infection ( MAC ), cerebral toxoplasmosi, and extrapulmonary cryptococcosis while receiving HAART is not well documented. |
| 38 | CMV and HIV Viral Burden and Development of CMV End-Organ Disease: a Prospective Study in HIV-Infected Subjects (ACTG 360). Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 38 Erice A, Tierney C, Hirsch M, Caliendo A, Weinberg A, Kendall M, Polsky B, The ACTG 360 Study Team; Univ. of Minnesota, Minneapolis BACKGROUND: In advanced HIV infection, the relationships between CMV burden, HIV burden, and risk for developing CMV end-organ disease (EOD) are not well established. METHODS: ACTG 360 was a 3-year observational study of CMV EOD in HIV-infected subjects without prior CMV EOD and a CD4 cell count of 50 cells/mm(3) withi |
| 39 | CMV Viraemia is an Independent Predictor of Disease Progression and Death in the Era of HAART. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 39 Deayton J, Sabin C, Johnson MA, Emery V, Griffiths P; Royal Free and Univ. Coll. Sch. of Med., London, UK BACKGROUND: Studies conducted prior to the introduction of HAART associated CMV viraemia with an increased risk of both development of CMV disease and death. As the natural history of CMV has since altered, this study aims to investigate whether CMV viraemia remains independently associated with disease progression and |
| 40 | Adipocyte-Derived Hormone Levels and their Corrlates in the HIV Lipodystrophy Syndrome. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 40 L. Kosmiski, D. Kuritzkes, K. Lichtenstein, and R. Eckel Leptin and adiponectin levels are altered in the HIV-LD. Leptin levels correlate with measures of adiposity and adiponectin with measures of body fat distribution. The levels of these hormones are strongly correlated with and independent predictors of insulin sensitivity in the HIV-LD. Adiponectin deficiency may contribute to the insulin resistance of this LD syndrome. |
| 41 | A Randomized Trial Comparing 2 4-Drug Antiretroviral Regimens with a 3-Drug Regimen in Advanced HIV Disease. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 41 Fischl M, Ribaudo H, Collier AC, Erice A, Giuliano M, Dehlinger M, Eron JJ, Saag M, Hammer S, Vella S, Feinberg J, The AIDS Clinical Trials Group 388 Team; Univ. of Miami, FL BACKGROUND: Optimal treatment for advanced HIV infection is not well defined. METHODS: ACTG 388 was a phase III open-label randomized study of lamivudine ( 3TC ) and zidovudine (ZDV) with either indinavir (IDV), |
| 42 | Atazanavir Plus Saquinavir Once Daily Favorably Affects Total Cholesterol (TC), Fasting Triglyceride (TG), and Fasting LDL Cholesterol (LDL) Profiles in Patients Failing Prior Therapy (Trial AI424-009, Week 48). Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 42 D. W. Haas*1, C. Zala2, S. Schrader3, A. Thiry4, R. McGovern4, and S. Schnittman4 In subjects who have failed a prior regimen, atazanavir/saquinavir once daily was safe and well tolerated, and it rapidly and durably suppressed HIV RNA and durably increased CD4. Atazanavir/saquinavir once daily lowered TC, LDL, and TG levels from baseline, whereas ritonavir/saquinavir twice daily produced prompt, marked, and sustained increases. The ability to improve serum lipid profiles in treatment-experienced subjects suggests that atazanavir may reduce the risk of cardiovascular events in this population. |
| 43 | Effect of Baseline Nucleoside-Associated Resistance on Response to Tenofovir DF (TDF) Therapy: Integrated Analyses of Studies 902 and 907 Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 43 Miller MD, Margot NA, Lu B; Gilead Sci., Foster City, CA BACKGROUND: Studies 902 and 907 were placebo-controlled, double-blind studies evaluating TDF when added to stable regimens in treatment-exp. Patients. 94% of patients had NRTI-resistance mutations at baseline (BL). TDF 300 mg therapy resulted in statistically significant mean HIV RNA reductions from BL to week 24 (DAVG |
| 44 | Crystal Structure of HIV-1 RT with Template-Primer Terminated with the Acyclic Nucleotide RT Inhibitor Tenofovir Suggests Mechanisms of Evading Resistance. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 44 Tuske S, Sarafianos S, Clark AD Jr, Ding J, Naeger LK, Miller MD, Gibbs C, Jerina DM, Hughes S, Arnold E; Ctr. for Advanced Biotechnology and Med., Piscataway, NJ BACKGROUND: The nucleotide reverse transcriptase inhibitor tenofovir retains potency against NRTI-resistant mutants of HIV-1 RT. We have employed structural studies to investigate the relationship between the acyclic nature of tenofovir and the mechanism of sensitivity to HIV-1 RT mutants. METHODS: A modified oligonucl |
| 45 | Efavirenz Hypersusceptibility Improves Virologic Response to Multidrug Salvage Regimens in ACTG 398. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 45 Mellors J, Vaida F, Bennett K, Hellmann NS, DeGruttola V, Hammer S, The ACTG 398 Study Team; Univ. of Pittsburgh, PA BACKGROUND AND METHODS: ACTG 398 assessed whether a second protease inhibitor (PI), combined with amprenavir (APV 1200 mg BID), abacavir (ABC 300 mg BID), efavirenz (EFV 600 qd), and adefovi |
| 46 | Different Pathways to Nelfinavir Genotypic Resistance in HIV-1 Subtypes B and G. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 46 Gomes P, Diogo I, Goncalves MF, Carvalho P, Cabanas J, Lobo MC, Camacho R; Hosp. Egas Moniz, Lisbon, Portugal BACKGROUND: Subtype G is the commonest non-B subtype in HIV-1-infected patients in Portugal (12% of the total number of infections). Although genotypic resistance to antiretroviral drugs has been extensively studied for HIV-1 subtype B, less is known about genotypic correlates for resistance on non-B subtypes. |
| 47 | Drug Resistant Replication Competent HIV-1 Occurs Initially in the CD45RO Subset of CD4 T Cells and Subsequently in CD45RA CD4 Lymphocytes Following Antiretroviral Therapy. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 47 Rose S, Perez E, Lamers S, Sleasman J, Goodenow M; Univ. of Florida Coll. of Med., Gainesville BACKGROUND: CD4 T cells are classified based on expression of CD45RA or CD45RO. Cell phenotypes reflect differences in cell half-lives, activation, and HIV-1 susceptibility. HIV-1 is found predominantly in the CD45RO CD4 subset of T cells that have a short life-span. CD4 lymphocytes and macrophages that are long-lived |
| 48 | Interruption/Stopping Antiretroviral Therapy and the Risk of Clinical Disease: Results from the EuroSIDA Study Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 48 Lundgren JD, Vella S, Paddam L, Blaxhult A, Vetter N, Clumeck N, Panos G, Fisher M, Katlama C, Phillips AN; EuroSIDA Coord Office, Hvidovre, Denmark BACKGROUND: Reports suggest that it has been relatively common for people to interrupt (or stop altogether) antiretroviral therapy. METHODS: We studied 3610 people within the EuroSIDA study who started a HAART regimen (3 drugs taken simultaneously). We assessed the tendency for therapy interruption and evaluated the re |
| 49 | Dynamics of HIV Rebound in Cerebrospinal Fluid (CSF) after Interruption of Antiretroviral Therapy (ART) Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 49 Ellis RJ, Letendre S, Frost SD, Leigh Brown AJ, Childers ME, McCutchan JA, HIV Neurobehavioral Res. Ctr; Univ. of California, San Diego BACKGROUND: Previously presented findings suggest that HIV in CSF represents a mixed viral population derived from at least 2 sources: extraneural trafficking, and local replication in neural tissues. Among patients with CD4 counts > 200, pleocytosis (elevated CSF leukocytes) typically accompanies CSF HIV RNA levels > |
| 50 | Viral Populations Emerging in Plasma during Sequential Structured Treatment Interruptions in Chronically HIV-Infected Individuals Are Genetically Distinct between Time-Points and Tissues Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 50 Martinez-Picado J, Frost SD, Marfil S, Puig T, Clotet B, Ruiz L; irsiCaixa Fndn., Badalona, Spain BACKGROUND: The sources of re-emerging HIV-1 in plasma during sequential structured treatment interruptions (SSTI) in asymptomatic infected patients have not been completely elucidated yet. Our goal was to determine whether viral populations from plasma RNA and PBMC DNA following STI are genetically distinct between ti |
| 51 | Recruitment of Tsg101 to Sites of Particle Assembly, Mediated by Short Peptide Motifs Is Required for Efficient HIV-1 and Ebola Virus Particle Budding Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 51 Martin-Serrano J, Zang T, Bieniasz PD; Aaron Diamond AIDS Res. Ctr., Rockefeller Univ., New York, NY BACKGROUND: Retroviral Gag proteins encode sequences, termed late or L-domains, that facilitate the final stages of particle budding from the plasma membrane. In HIV-1, L-domain function is provided by sequences in the p6 protein. Recently, p6 was reported to bind a cellular protein, Tsg101. The objective of this study |
| 52 | Overexpressing the E2-Like Domain of Tsg 101 Supresses HIV-1 Budding by Blocking p6 Late Domain Activity Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 52 Demirov D, Ono A, Freed E; NIH, Bethesda, MD BACKGROUND: A 6 kDa, Pro-rich protein, p6, is encoded by the C-terminus of the HIV-1 gag gene. Previously, we demonstrated that a highly conserved Pro-Thr-Ala-Pro (PTAP) sequence near the N-terminus of p6 is essential for efficient virus budding. Mutations in this motif result in a dramatic accumulation of tethered vir |
| 53 | Formation of an HIV-1 Core of Optimal Stability Is Crucial for Viral Replication Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 53 Forshey BM, von Schwedler U, Sundquist WI, Aiken C; Vanderbilt Univ. Sch. of Med., Nashville, TN BACKGROUND: Virions of HIV-1 and other lentiviruses contain conical cores comprised of an internal ribonucleoprotein complex surrounded by a protein shell composed of the viral capsid protein (CA). Although genetic studies have implicated CA in both early and late stages of the virus replication cycle, the mechanism of |
| 54 | HIV-1 Vif Is Associated with HP68, a Host Protein that Appears to Be Essential for Immature Capsid Formation. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 54 Klein K, Lingappa J; Univ. of Washington, Seattle BACKGROUND: Using a system that reconstitutes immature HIV-1 capsid formation, we identified a cellular factor (HP68) that selectively associates with HIV-1 Gag polypeptides in a variety of systems including HIV-1-infected T cells. Studies using dominant negative mutants of HP68 in cells as well as depletion-reconstitu |
| 55 | The Identification of Cellular Host Factors Important for the HIV-1 Vif Phenotype Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 55 Sheehy AM, Malim MH; Univ. of Pennsylvania, Philadelphia BACKGROUND: The Vif protein of human immunodeficiency virus (HIV-1) is absolutely required for the productive and sustained infection of human peripheral blood lymphocytes (PBLs) and certain transformed lymphocytic T-cell lines, but is not required in other T-cell lines. This requirement for Vif in different cell lines |
| 56 | A C-Terminal Nuclear Localization Signal in HIV-1 Integrase Mediates Viral Nuclear Import Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 56 D. R. Kaufman, B. Chai, J. Chang, N. Genoud, A. Steed, and M. Muesing* These results indicate that the integrase NLS plays a significant role in the nuclear import of the HIV-1 genome. |
| 57 | Interaction of HIV-1 Vpr with Cdc25C: Implications for G2 Arrest Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 57 Goh WC, Manel N, Emerman M; Fred Hutchinson Cancer Res. Ctr., Seattle, WA BACKGROUND: The Vpr gene of HIV-1 encodes a 14-kD protein that prevents cells from passing through mitosis by arresting them in the G2 phase of the cell cycle. This property is highly conserved among all known primate vpr alleles and likely serves an important function in viral pathogenesis. Vpr increases viral express |
| 58 | HIV Infection Results in G2 Cell Cycle Arrest In Vivo Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 58 Sherman MP, Neidleman JA, Williams S, de Noronha C, Eckstein D, Kahn J, Hecht R, Warmerdam M, Greene WC; Gladstone Inst. of Virology and Immunology BACKGROUND: The HIV-1 genome encodes the small, multifunctional Vpr protein that enhances HIV replication in macrophages and, when over-expressed in cultured primate cell lines, induces G2 cell cycle arrest. This arrest has been proposed to provide a favorable intracellular milieu for HIV LTR mediated transcription and |
| 59 | CD4-Bound Conformation of HIV-1 gp120 Improved by Introduced Disulfide Bonds. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 59 Xiang SH, Kwong P, Vainshtein J, Sodroski J; Dana-Farber Cancer Inst., Boston, MA BACKGROUND: We previously reported that the Phe-43 cavity-filling mutant (375 S/W) of HIV-1 YU2 gp120 was partially stabilized in a CD4-bound conformation. This mutant largely reduced the binding of all 5 tested CD4-binding-site (CD4BS) antibodies, but did not disrupt CD4 and CD4-induced (CD4i) antibody binding. Here w |
| 60 | Effects of Compartmentalization on HIV-1 Nef Evolution Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 60 Pillai S, Guatelli J, Spina C, Letendre S, Ellis RJ, Wong JK, Richman DD; Univ. of California, San Diego BACKGROUND: One of the primary functions of the HIV-1 Nef protein in vivo is evasion of the cytotoxic T-lymphocyte (CTL) response, via down-modulation of MHC class I expression at the cell surface. Recent data suggest that the extent of MHC down-modulation by Nef varies with respect to disease stage, possibly due to fl |
| 61 | Factors Associated with AIDS Dementia Complex Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 61 Brew B, Fulham M, Garsia R; St. Vincent's Hosp., Sydney, Australia BACKGROUND: Recently, the incidence of AIDS dementia complex (ADC) has been found to have halved as a consequence of the introduction of highly active antiretroviral therapy (HAART) but it is unknown whether this can be maintained with long-term HAART. Moreover, it is not clear what factors are important in ADC develop |
| 62 | Relationship of Cerebrospinal Fluid (CSF) White Blood Cells (WBCs) to CSF and Systemic HIV Infection: Cross-Sectional and Longitudinal Analysis Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 62 Price RW, Nilsson A, Deeks SG, Verotta D, Grant RM; Univ. of California, San Francisco BACKGROUND: Though common in HIV infection, CSF pleocytosis is not well characterized. This study aimed to further define the relationship among 4 salient interacting variables: CSF WBCs, CSF, and plasma HIV concentrations, and blood CD4 counts. METHODS: Prospective study of a convenience sample using 2 approaches: cro |
| 63 | Expression of DC-SIGN in Cultured Microglia and in the CNS of Individuals with and without HIV Dementia (HIV-D) Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 63 Shawver L, Baribaud F, Doms RW, Pardo-Villamizar C, McArthur J, Gonzalez-Scarano F; Univ. of Pennsylvania, Philadelphia BACKGROUND: DC-SIGN, a type II membrane protein, contains a C-type lectin domain that binds HIV strains of both X4 and R5 phenotypes, and has been implicated in the entry of HIV into dendritic cells, which can then transport the virus into lymph nodes and transfer it to other susceptible cells such as CD4+ lymphocytes. |
| 64 | Expression and Functional Analysis of CXCR4 in the Central Nervous System. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 64 J. Wang* and D. Gabuzda These results suggest that interactions between HIV-1 virions and CXCR4 expressed on a subset of neurons, astrocytes, and NSC contribute to neurodegenerative mechanisms in HIV-1 infection and raise the possibility that different CXCR4 conformations on neurons and astrocytes may underlie some cell-type-dependent functions of chemokine receptors in the CNS. |
| 65 | Soluble Fas in the Cerebrospinal Fluid is a Potential Marker for the Severity and Prognosis of HIV-Associated Dementia. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 65 A. Towfighi*, R. Skolasky, C. St. Hillaire, K. Conant, and J. McArthur The astrocyte product sFas is elevated in CSF in HIV-D and correlates with dementia severity. Levels are higher in progressive dementia, corroborating observations with autopsy tissue. CSF sFas may be a useful marker for assessing severity and prognosis of HIV-D. |
| 66 | Differences in HIV-1 V1/V2 and V3 Populations between Blood Plasma and Cerebral Spinal Fluid Suggest at Least Partial Virologic Compartmentalization. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 66 Ritola K, Nelson JA, Robertson K, Hall C, Fiscus SA, Swanstrom R; Univ. of North Carolina, Chapel Hill BACKGROUND: During HIV-1 infection, the gp120 subunit of the viral Env protein is under immune pressure resulting in sequence diversification which allows evasion of the host response. This pressure to evolve results in the appearance of multiple viral variants within a subject. The env gene variable regions 1 and 2 (V |
| 67 | Distribution of HIV env and pol Variants in CSF and Plasma of Patients with and without Antiretroviral Therapy. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 67 J. K. Wong*1,2, S. Letendre1,3, T. Macaranas1, C. Ignacio1, O. A. Daly2, H. F. Guenthard4, M. C. Strain1, S. D. W. Frost1,5, S. Pillai1, B. Good1, M. Furtado7, S. Wolinsky6, I. Grant3, D. D. Richman1,2, and J. A. McCutchan1 Consistent with previous observations, these results suggest that viral populations in CSF and plasma are frequently distinct. However, failure of drug therapy and the emergence of drug resistance appears to be associated with equilibration of viral populations in CSF and blood. Because of the neurotoxic potential attributed to specific HIV envelope types, such perturbations in the population genetics of HIV may have important clinical implications. |
| 68 | A Murine Model for HIV-Associated Dementia: An Inducible Tat Transgenic Mouse Model. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 68 Kim BO, Liu Y, He JJ; Indiana Univ. Sch. of Med., Indianapolis BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) Tat protein, a potent transactivator of viral and cellular genes, has been proposed as a key agent in the pathogenesis of acquired immune deficiency syndrome (AIDS)-related disorders, including HIV-1-associated dementia . HIV-1 Tat protein is neurotoxic both i |
| 69 | Increasing Prevalence of Neuropathy in the Era of Highly Active Antiretroviral Therapy (HAART) Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 69 Cherry C, McArthur J, Costello K, Woolley I, Mijch A, Wesselingh S; Monash Univ., Alfred Hosp., Melbourne, Victoria, Australia BACKGROUND: Sensory neuropathy (SN) is the most common neurological complication of HIV infection. Prevalence data for SN are predominately derived from cohorts studied before the introduction of HAART, with observed risk factors for SN including prolonged illness and advanced immunosuppression. We aimed to describe th |
| 70 | An in Vitro Model of Antiretroviral Toxic Neuropathy in Dorsal Root Ganglion Sensory Neurons Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 70 Keswani S, Hasan C, McArthur J, Griffin J, Hoke A; Johns Hopkins Univ. Sch. of Med., Baltimore, MD BACKGROUND: Nucleoside analogue reverse transcriptase inhibitors (NRTIs) are an essential component of HAART, substantially reducing the morbidity and mortality of HIV infection. However, the use of many of these drugs has been associated with a painful, sensory neuropathy, possibly via neuronal mitochondrial dysfuncti |
| 71 | Both Innate and Adaptive Immune Responses Confer Protection in SHIV89.6 Infected Rhesus Macaques Challenged with Pathogenic SIVmac239 Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 71 Abel K, Compton L, Rourke T, Lu D, Fritts L, Miller CJ; Ctr. for Comparative Med., Davis, CA Backround: Although attenuated lentiviral vaccines will not be used in humans, they are highly effective in animal models. There is evidence that cellular antiviral immune responses (CTL) and innate effector molecules (chemokines, CAF) can control virus replication, but their relative role in antiviral immunity is stil |
| 72 | Immunogenicity and Protective Efficacy of ISS ODN Adjuvanted Inactivated SIV Containing Functional Envelope Glycoprotein against IV SIVmac239 Challenge. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 72 Arthur LO, Rossio JL, Piatak M Jr, Flynn BM, Desrosiers RC, Hoxie J, Raz E, Richman DD, VanNest G, Henderson L, Lifson JD; SAIC, Frederick, MD BACKGROUND: We evaluated the immunogenicity and protective efficacy of an inactivated virus immunogen, with and without CpG motif containing immunostimulatory oligodeoxynucleotides (ISS ODN), in the rhesus/SIVmac239 challenge model. METHODS: Inactivated virions with high levels of functional envelope glycoprotein were |
| 73 | Vaccination with Autologous Dendritic Cells Pulsed with AT-2-Inactivated Whole Virus Provides Partial Protection from Pathogenic SIV Challenge Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 73 Y.-D. Zhu*1, K. Koo1, 2, W. Sutton1, L. Kuller3, S.-L. Hu2, 3, R. Benveniste4, E. Thomas5, J. D. Lifson6, and N. Haigwood1 Vaccination with SIV-pulsed autologous DCs is safe and can induce both T- and B-cell immunity to SIV that can protect from infection and disease in a majority of macaques. Our data suggest that both cellular and humoral immune responses are contributing to the control of virus replication after pathogenic virus challenge. Dendritic cells hold promise to deliver antigens for antiviral vaccines. |
| 74 | Viremia Containment Following Mucosal Challenge with SIVmac251 Correlates with SIV-Specific CTL and Lymphoproliferative Responses Induced by a DNA-SIV and NYVAC-SIV Prime/Boost Regimen Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 74 Hel Z, Nacsa J, Tryniszewska E, Tsai WP, Montefiori D, Felber BK, Pavlakis GN, Tartaglia J, Franchini G; NCI, NIH, Bethesda, MD BACKGROUND: An important goal in the development of a vaccine for HIV-1 is the induction of cell-mediated immune responses able to contain viral replication. METHODS: A study was designed whereby vaccination of macaques with DNA expressing the Gag and Env proteins of SIV followed by immunizations with the highly attenu |
| 75 | Enhanced Protective Efficacy of Vaccinia Virus/Protein Vaccine Regimen Containing Polyvalent Envelope Against a Pathogenic SHIV in Rhesus Macaques. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 75 Kim YB, Han DP, Willey R, Plishka R, Buckler-White A, Byrum R, Martin MA, Cho MW; NIH, Bethesda, MD BACKGROUND: Due to difficulties in eliciting broadly reactive neutralizing antibodies against HIV-1, the potential benefits of immunization with the viral envelope glycoprotein have been largely unappreciated. In this study we compared the protective efficacy of 2 vaccine candidates, one that contains Gag-Pol alone and |
| 76 | Passive Neutralizing IgG Treatment During the Acute Phase Improves Host Immunity and Disease Outcome in SIV-Infected Macaques Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 76 Haigwood N, Choi P, Fischer J, Sutton W, Yaraei K, Richardson B, Kuller L, Anderson D, Hu SL, Hirsch V; Seattle BioMed. Res. Inst., WA BACKGROUND: Passive immunotherapy is a potential adjunct treatment for HIV infection, particularly in post-exposure prophylaxis (PEP). We have shown that neutralizing antibodies (IgG) given passively in the acute phase delays disease in a moderately pathogenic SIV model. The goal of this study was to test this hypothes |
| 77 | Neutralizing Antibodies Applied to the Mucosal Surface, or Preincubated with Challenge Virus ex Vivo, Fail to Protect Macaques Against SHIV-Challenge. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 77 Lewis MG, Greenhouse J, Yalley-Ogunro J, Shaw N, Silvera P, VanCott TC, Stiegler G, Katinger H, Mascola JR; Southern Res. Inst. Frederick, MD BACKGROUND: The potential of passive immune-based prevention of HIV transmission in humans was studied. We have previously shown that neutralizing monoclonal antibodies 2F5 and 2G12 protect animals from lentivirus infection in vivo when administered by intravenous injection. The studies reported here were performed to |
| 78 | Novel Broadly Cross-Reactive HIV-1-Neutralizing Human Monoclonal Antibody Selected for Binding to gp120-CD4-CCR5 Complexes. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 78 Moulard M, Phogat S, Shu Y, Xiao X, Parren PW, Binley JM, Zhang M, Robinson J, Burton DR, Dimitrov DS; Scripps Res. Inst., La Jolla, CA BACKGROUND: HIV-1 entry into cells involves formation of a complex between gp120 of the viral envelope glycoprotein (Env), a receptor (CD4), and a co-receptor (CCR5, CXCR4). Here we provide evidence that purified JR-FL gp120-CD4-CCR5 complexes exhibit an epitope recognized by a novel human antibody Fab (X5). METHODS: T |
| 79 | Construction and Characterization of HIV-1 Subtype-C-Based, Dual-Promoter DNA Vaccines. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 79 Huang Y, Chen Z, Zhang W, Song Y, Gurner D, Ho D; Aaron Diamond AIDS Res. Ctr., Rockefeller Univ., New York, NY BACKGROUND: Administration of a DNA vaccine is limited by restrictions on anatomic sites, volume of inoculum, and the number of genes that can be expressed. We therefore undertook to design, construct, and evaluate 2 DNA vaccines, each comprising 2 promoters for expression of 2 or more HIV-1 subtype-C genes. METHODS: W |
| 80 | Improved Candidate DNA Vaccines against HIV-1 Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 80 Rosati M, Eyler P, Valentin A, Trivedi H, Biragyn A, Kwak LW, Markham P, Woodward R, von Gegerfelt A, Miller N, Felber BK, Pavlakis GN NCI, NIH, Frederick, MD BACKGROUND: DNA-based immunogens promise to provide simple and cost-effective vaccines, although further development is needed in the generation of expression vectors and delivery systems. To improve the efficiency of DNA candidate vaccines, we have generated several Rev-independent vectors that express HIV and SIV str |
| 81 | Mutations in the HIV-1 gp41 Cytoplasmic Tail that Expose CD4-Induced Epitopes in gp120 Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 81 Wyss S, Edwards TG, Baribaud F, Romano J, Vance PJ, Zolla-Pazner S, Doms RW, Hoxie J; Univ. of Pennsylvania BACKGROUND: We have described a variant of HIV/IIIB, termed 8x, which could utilize CXCR4 in the absence of CD4. The 8x monomeric gp120 bound directly to CXCR4 in the absence of CD4 and exhibited stable exposure of CD4-induced (CD4i) epitopes recognized by monoclonal antibodies 17b and 48d. Requirements for CD4-indepen |
| 82 | Use of Entry Inhibitors to Probe Envelope:Receptor Interactions. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 82 Reeves J, Puffer B, Ahmad N, Derdeyn C, Sharron M, Edwards T, Carlin D, Harvey P, Pierson T, Hunter E, Doms RW; Univ. of Pennsylvania, Philadelphia BACKGROUND: The envelope protein of HIV is composed of an outer gp120 glycoprotein and a transmembrane gp41 protein that assemble as trimers on the surface of virions. gp120 interacts with CD4 and a 7-transmembrane chemokine receptor molecule (usually CCR5 or CXCR4) to initiate infection of target cells. The interactio |
| 83 | Identifying Binding Sites on CXCR4 and gp120 Using CD4-Independent HIV-2 Env Proteins Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 83 G. Lin*1, F. Baribaud1, J. Romano1, M. Alizon2, R. W. Doms1, and J. Hoxie1 CD4-independent X4-tropic HIV Env proteins appear to exhibit a high affinity for CXCR4 and will be particularly useful in identifying critical contact residues for this interaction. Current efforts are aimed at quantifying these interactions and further mapping binding sites on both CXCR4 and gp120. |
| 84 | Localization and Mobility of the HIV Receptor CD4 and Co-Receptor CCR5: Implications for HIV Fusion and Entry Events. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 84 Steffens CM, Mann D, Hope TJ; Univ. of Illinois, Chicago BACKGROUND: The complicated sequence of events leading to HIV fusion and entry into target cells involves the recruitment of receptor and co-receptor by the viral envelope. Likely, a specific complex composed of multiple copies of each protein must be formed. Recent observations by our laboratory and others suggest tha |
| 85 | HIV-1-Mediated Signal Transduction through CCR5 Allows Infection of Resting Memory T Cells. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 85 J. Vasudevan*, A. Matthews, C. O'Connor, A. Meek, and D. Camerini Our data implicate HIV-1-mediated signaling via CCR5 in the infection of normal, resting memory T cells. |
| Abstracts 86 to 90 are not available electronically | |
| 91 | The Presence of HLA-B*5701, -DRB1*0701, and -DQ3 Is Highly Predictive of Hypersensitivity to the HIV Reverse Transcriptase Inhibitor Abacavir Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 91 Mallal S, Nolan D, Witt C, Masel G, Martin A, Moore C, Sayer D, Castley A, Mamotte C, Maxwell D, James I, Christiansen F; Ctr. for Clin. Immunology and Biomed. Statistics, Royal Perth Hosp., Perth, Australia BACKGROUND: The use of abacavir , a potent HIV nucleoside analogue reverse transcriptase inhibitor, is complicated by a potentially life-threatening hypersensitivity syndrome in approximately 5% of cases. Genetic factors influencing the immune response to abacavir may confer susceptibility. METHODS: Major histocomp |
| 92 | HLA-B57 and TNF-α Variants Associated with Hypersensitivity Reactions to Abacavir among HIV-1-Positive Subjects. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 92 Hetherington S, Hughes A, Mosteller M, Shortino D, Baker K, Lai E, Stocum M, Roses A; GlaxoSmithKline, Res. Triangle Park, NC BACKGROUND: Hypersensitivity to abacavir is a well-characterized clinical syndrome occurring in 4% of patients. Features of the syndrome are consistent with an immunologic process possibly influenced by genetic factors. 90% of cases occur within the first 6 weeks of therapy. METHODS: A retrospective case-control pr |
| 93 | Are Episodes of Transient Viremia ("Blips" in HIV RNA) Predictive of Virologic Failure in Heavily Treatment-Experienced Patients? Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 93 D. Havlir*1, R. Bassett2, V. DeGruttola2, S. Hammer3, R. Gulick4, and J. Mellors5 for the ACTG 359 and 398 Teams Even in highly treatment-experienced patients on multidrug salvage regimens, transient increases in HIV RNA do not predict virologic failure (within 38 weeks) in patients who have achieved plasma HIV-1 RNA < 50 copies/mL on at least 1 occasion. Defining virologic failure by the occurrence of 1 or more episodes of HIV RNA > 50 copies/mL, after initial suppression to < 50 copies/mL is too stringent. These observations have implications for clinical practice and endpoints in clinical trials. |
| 94 | Viral Blip Dynamics during HAART. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 94 Di Mascio M, Markowitz M, Louie M, Hurley A, Ho D, Perelson AS; Los Alamos Natl. Lab., NM BACKGROUND: Intermittent episodes of low-level viremia (blips) are often observed in well-suppressed, HAART-treated patients. It has been reported that viral blips do not correlate with the emergence of new HAART-related mutations; however, increased frequency of blips correlates with slower decay of latently infected |
| 95 | Persistence of Transmitted Drug Resistance among Subjects with Primary HIV Infection not Receiving Antiretroviral Therapy Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 95 Little SJ, Daar ES, Holte S, Frost SD, Routy JP, Markowitz M, Collier AC, Margolick J, Koup R, Conway B, Connick E, Kilby M, Wrin T, Petropoulos CJ, Hellmann NS, Richman DD; Univ. California, San Diego Purpose: To evaluate the persistence and altered replication capacity (fitness) of transmitted antiretroviral (ARV) resistant variants among untreated subjects with primary HIV infection. METHODS: ARV drug susceptibility and replication capacity were measured using a single replication cycle assay (ViroLogic). ABI sequ |
| 96 | Mixed Infection with Multidrug Resistant (MDR) and Wild Type HIV Strains in Primary HIV Infection (PHI): Early Viral Rebound Suggests Loss of Immune Control. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 96 Daar ES, Frost SD, Wong JK, Hellmann NS, Wrin T, Petropoulos CJ, Richman DD, Pitt JA, Little SJ, Leigh Brown AJ; Cedars-Sinai Med. Ctr., Univ. of California, Los Angeles BACKGROUND: We described a patient with PHI with an MDR virus, who without receiving therapy precipitously lost all evidence of resistance in conjunction with an increase in viral load. Initial sequence analysis revealed many changes between resistant (strain 1) and susceptible (strain 2) variants raising the possibili |
| 97 | Initiation of Treatment before Seroconversion Increases the Rate of Clearance of the Latent Reservoir. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 97 Strain MC, Little SJ, Daar ES, Gunthard H, Spina C, Lam RY, Daly OA, Ignacio C, Macaranas T, Kwok S, Christopherson C, Santangelo J, Pitt J, Richman DD, Wong JK; Univ. of California San Diego BACKGROUND: The slow clearance of infected, resting CD4+ T cells in chronically-infected patients poses a major obstacle to viral eradication. This cellular reservoir of HIV is established even prior to seroconversion. Its decay has not been previously quantified in patients initiating treatment in primary infection. W |
| 98 | Acute Phase CTL Escape Is a Hallmark of Simian Immunodeficiency Virus Infection Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 98 D. H. O’Connor*1, T. M. Allen1, T. U. Vogel1, P. Jing1, I. P. DeSouza1, E. Dodds1, E. J. Dunphy1, C. Melsaether1, B. Mothé1, H. Horton1, A. L. Hughes2, and D. I. Watkins1 Previous studies have demonstrated that CTL that only require low peptide concentrations for stimulation (high functional avidity) are particularly effective at controlling viral infections. Our results suggest that acute viral escape from CTL is a hallmark of SIV infection and that CTL with high functional avidity rapidly select for these escape variants. These findings may have implications for the choice of epitopes that should be included in candidate HIV vaccines. |
| 99 | Accumulation of DC-SIGN+ CD40+ Dendritic Cells with Reduced CD80 and CD86 Expression in Lymphoid Tissue during Acute HIV-1 Infection Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 99 Lore K, Sonnerborg A, Brostrom C, Goh L, Perrin L, McDade H, Stellbrink HJ, Gazzard B, Weber R, Napolitano LA, van Kooyk Y, Andersson J; NIAID Vaccine Res. Ctr., NIH, Bethesda, MD BACKGROUND: The dendritic cells (DCs) may serve as a target cell for mucosal HIV-1 transmission in addition to their key role in antigen presentation and activation of naïve T cells. The interdigitating DCs in vivo in lymphoid tissue were assessed in HIV-1-infected patients with regard to maturation, expression of cyto |
| 100 | Correlates of Viral Diversity in Primary HIV-1 Infection in Women Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 100 Sagar M, Lavreys L, Baeten J, Richardson B, Mandaliya K, Kreiss J, Overbaugh J; Fred Hutchinson Cancer Res. Ctr., Seattle BACKGROUND: The majority of women are infected by multiple viral variants while the remainder harbor a homogeneous virus population early in their infection. It is unknown what factors predict whether multiple HIV-1 variants will be transmitted and what impact the genetic complexity of the infecting virus has on diseas |
| 101 | Impact of Thymectomy on the Peripheral T-Cell Pool in Rhesus Macaques before and after Infection with SIV Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 101 Arron ST, Gettie A, Blanchard J, Ho D, Zhang L; Aaron Diamond AIDS Res. Ctr., Rockefeller Univ., New York, NY BACKGROUND: The goal of this study is to define the role of the thymus in peripheral T-cell homeostasis and to assess the significance of thymic output in SIV infection by surgical removal of the thymus in juvenile rhesus macaques. METHODS: 9 juvenile rhesus macaques were thymectomized and 8 underwent sham surgery. Blo |
| 102 | Kinetic Subpopulations of T Cells in Humans: Effects of HIV-1 Infection Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 102 Hellerstein M, Hoh R, Hanley M, Cesar D, Lee D, Neese R, McCune JM; Univ. of California, San Francisco BACKGROUND: Following an antigen-driven proliferative response, some daughter T cells differentiate into effector-type cells while others differentiate into long-lived, true memory cells. Functional subpopulations of short-lived (effector) and long-lived (true memory) T cells have been proposed to exist within the phen |
| 103 | Prolonged and Preferential Survival of CD4+ T Lymphocytes in HIV-Infected Patients Receiving IL-2 Therapy. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 103 Kovacs J, Lempicki RA, Sidorov IA, Adelsberger JW, Kelly G, Metcalf JA, Davey RT, Falloon J, Polis MA, Tavel J, Stevens R, Lambert L, Hosack D, Issaq HJ, Fox S, Leitman S, Baseler MW, Masur H, Dimitrov DS, Lane HC; Clin. Ctr., NIH, Bethesda, MD BACKGROUND: Intermittent interleukin-2 ( IL-2 ) therapy can lead to substantial and sustained increases in CD4+ T-cell numbers in HIV-infected patients without increasing CD8+ T-cell numbers. While increased proliferation has been identified as one possible mechanism leading to the increase in CD4+ cells, the effects o |
| 104 | Intermittent IL-2 in HIV-Infected Patients Leads to Peripheral Expansion of a Novel Subset of Naive CD4+ T Cells. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 104 I. Sereti*1, V. Natarajan2, J. W. Adelsberger2, J. A. Metcalf1, H. Martinez-Wilson1, K. Anthony1, J. Kovacs3, and H. C. Lane1 Intermittent IL-2 in HIV-infected patients leads to expansion of a unique population of naïve CD4+ T cells expressing CD25 that have a distinct phenotype and a significantly lower TREC content compared to naïve CD4+/CD25- cells. These data suggest that these cells do not represent recent thymic emigrants but rather the product of peripheral T-cell expansion. |
| 105 | HIV-1 Core Envelope Glycoproteins Deficient in T-Cell Helper Epitopes. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 105 Grundner C, Kang J, Koch M, Sodroski J, Wyatt R; Dana-Farber Cancer Inst., Boston, MA BACKGROUND: The development of an effective HIV-1 vaccine will likely need to efficiently elicit broadly-neutralizing antibodies directed against conserved receptor-binding regions of the HIV-1 gp120 envelope glycoprotein (Env). The generation of mature antibody responses requires the assistance of T-cell help from act |
| 106 | A Novel Approach to the Analysis of Specificity, Clonality, and Frequency of HIV-Specific T-Cell Responses Reveals a Mechanism for Lack of Escape within an Immunodominant Epitope. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 106 Douek D, Betts M, Brenchley J, Hill B, Ambrozak D, Ngai KL, Casazza J, Koup R; NIAID Vaccine Res. Ctr., NIH, Bethesda, MD BACKGROUND: Escape from the CD8+ T-cell response through mutations within encoded epitopes can lead to loss of immune control of human immunodeficiency virus (HIV) replication. Theoretically, escape from CD8+ T cell recognition is less likely when multiple T-cell receptors (TCR) target individual MHC/peptide complexes, |
| 107 | Enhancement of HIV-1-Specific CTL Responses in the Peripheral Blood during STI is Largely Due to Redistribution of Pre-Existing Virus-Specific CD8+ T Cells from the Lymph Nodes Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 107 Altfeld M, Lunzen JV, Frahm N, Yu X, Eldridge RL, Stellbrink HJ, Walker B; Partners AIDS Res. Ctr., Boston, MA BACKGROUND: To date, most studies have focused on the characterization of HIV-1-specific immune responses in the peripheral blood (PB) of infected individuals. This study compared CTL responses in PB and lymph nodes (LN) and assessed the dynamics of these responses during antiretroviral treatment and supervised treatme |
| 108 | HIV-Specific Cellular Immunity and Partial Control of Drug-Resistant vs Wild-Type Viremia Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 108 Deeks SG, Sinclair E, Harris JM, Maecker HT, Bredt B, Hagos E, Martin J, McCune JM; Univ. of California, San Francisco BACKGROUND: HIV-specific CD4 and CD8 T cells are key determinants of the virologic set-point in untreated patients. It is not known if HIV-specific cellular immunity plays a role in determining steady-state viral load in treated patients, particularly those who maintain partial virologic suppression despite the emergen |
| 109 | Constitutive and Induced Expression of DC-SIGN on Dendritic Cell and Macrophage Subpopulations in Situ and in Vitro Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 109 Soilleux EJ, Morris LS, Leslie G, Chehimi J, Luo Q, Levroney E, Trowsdale J, Montaner LJ, Doms RW, Weissman D, Coleman N, Lee B; Univ. of Cambridge, UK BACKGROUND: DC-SIGN is a C-type lectin highly expressed on the surface of immature dendritic cells (DCs) that mediates efficient infection of T cells in trans by its ability to bind HIV-1, HIV-2, and SIIn addition, the ability of DC-SIGN to bind adhesion molecules on surfaces of naïve T cells and endothelium also sugge |
| 110 | Cholesterol is Essential for Chemokine Binding to Receptors, CCR5 and CXCR4: Implications for HIV Infection. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 110 D. H. Nguyen* and D. D. Taub Together, these data demonstrate that cholesterol and lipid rafts are important for the maintenance of chemokine receptor conformation and are necessary for both the binding and function of chemokine receptors, CCR5 and CXCR4. We propose that the inhibition of HIV infection by BCD treatment of T cells may be due to a loss in binding and fusion of HIV env mediated by chemokine receptors. |
| 111 | Combination Antiretroviral Therapy Corrects the Disruptions in the TCR Vbeta Repertoire within CD45RA CD8 T Cells of HIV-Infected Children. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 111 Kou ZC, Puhr JS, Goodenow M, Sleasman J; Univ. of Florida, Gainesville BACKGROUND: HIV-1 infection disrupts thymic output and skews normal maturation of CD8 T cells in infected children. Infection also results in alterations within the TCR repertoire. Control of viral replication through HAART should reverse these virus-induced abnormalities and restore TCR diversity. METHODS: Using TCR s |
| 112 | Characterization of HIV-1 Specific Cellular Immune Responses in Stably Suppressed or Viremic Pediatric Patients Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 112 Papasavvas E, Rutstein R, Moore EC, Thiel B, Pistilli M, Mackiewicz A, Jordan KA, Sandberg JK, Ortiz GM, Nixon DF, Montaner LJ; Wistar Inst., Philadelphia, PA BACKGROUND: This study aimed at the characterization of cellular immune responses in HIV-infected children and adolescents. METHODS: 3 populations of HIV-infected children and adolescents were studied: Patients with viral suppression on medications (undetectable) for >6 months (n=24, median HIV-1 RNA=40); patients with |
| 113 | Lactic Acidemia in Infants Exposed to Perinatal Antiretroviral Therapy. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 113 Alimenti A, Ogilvie G, Burdge D, Money D, Forbes J; Univ. of British Columbia, Vancouver, Canada This is one of the first prospective observational studies describing lactic acidemia in HIV uninfected infants exposed to HAART during the perinatal period. The hyperlactatemia was noted in 92% of the infants, and was above 5 mmol/L in one third. We hypothesize that the persistent hyperlactatemia is a consequence of mitochondrial toxicity from the transplacental and neonatal exposure to antiretroviral agents, as well as of impaired hepatic lactate clearance. Further study is required to determine the factors impacting on the hyperlactatemia and its clinical significance. Clinical follow-up and monitoring of lactate levels is recommended during the first 6 months of life in all infants exposed to perinatal HAART. |
| 114 | Mother-to-Child HIV Transmission Rates According to Antiretroviral Therapy, Mode of Delivery, and Viral Load (PACTG 367). Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 114 D. Shapiro*1, R. Tuomala2, R. Samelson3, S. Burchett4, G. Ciupak5, J. McNamara6, H. Pollack7, and J. Read8 Over time, transmission rates decreased and multi-agent ART use and ECS increased. TR were significantly lower with more intensive ART and lower plasma HIV RNA level, but did not differ according to delivery mode. Among women with last antenatal RNA <1000 copies/mL, TR were low across ART types and delivery modes. |
| 115 | Response to Primary Immunization to Tetanus, Diphtheria, H. influenzae Type B and Measles in HIV-Infected Children on HAART. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 115 Pracanica A, Russo P, Zaccarelli-Filho CA, Succi R, Santos A, Weckx L, de Moraes-Pinto MI; Fed. Univ. of Sao Paulo, Brazil BACKGROUND: Studies in the pre-HAART era have shown that HIV-infected children had a poor response to immunization. Children on HAART may have a different response to vaccination. METHODS: 15 HIV-infected children (HIV) were compared to 32 seroreverters (SR) and to 27 healthy children born to HIV-negative mothers (CNT) |
| 116 | Association between Mother and Infant Class I and Class II HLA and of Their Concordance with the Risk of Perinatal HIV-1 Transmission Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 116 A. Polycarpou*1, C. Ntais1, B. T. Korber2, H. A. Elrich3, R. Winchester4, P. Krogstad5, S. Wolinsky6, T. Rostron7, S. L. Rowland-Jones7, A. J. Ammann8, and J. P. A. Ioannidis1 for the Ariel Project HLA alleles, and in particular the class I concordance between maternal and neonatal HLA, may regulate the risk of perinatal HIV-1 transmission. |
| 117 | HIV-Specific CD8+ T Cells Are Present at a High Frequency in Breast Milk from HIV-Infected Women Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 117 Sabbaj S, Edwards B, Ghosh M, Semrau K, Mulligan M, Goepfert P, Aldrovandi G; Univ. of Alabama, Birmingham BACKGROUND: It is estimated that a third to half of infants in the developing world contract HIV via breast milk. However, most breast-fed infants avoid infection despite daily ingestion of massive amounts of HIV. Factors controlling HIV in breast milk are poorly understood. Since CTL responses have been shown to play |
| 118 | CCR5 Genotype and Susceptibility to Transmission of HIV-1 in Women Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 118 S. Philpott1, B. Weiser1,2, P. Tarwater3, S. Vermund4, C. Kleeberger3, S. Gange3, K. Anastos5, M. Cohen6, R. Greenblatt7, A. Kovacs8, H. Minkoff9, M. Young10, M. Miotti11, M. Dupuis1, C. Chen1, and H. Burger*1 The CCR5 Δ32 heterozygous genotype may confer partial protection from HIV-1 infection in women. Such protection may reflect differences in routes and mechanisms of transmission to women as compared to men. In addition, among our multiethnic, multiracial, geographically dispersed U.S. cohort, the Δ32 deletion was much more common in Caucasians than in other groups. Because the protective Δ32 deletion is rare in Africans and Asians, it seems plausible that differential genetic susceptibility contributes to the rapid heterosexual spread of HIV-1 in Africa and Asia. |
| 119 | Lack of Effect of HAART on HPV DNA Levels in the Female Genital Tract. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 119 Conley LJ, Bush TJ, Ellerbrock TV, Lennox J, Wu F, Evans-Strickfaden T, Hart CE, Wright TC; CDC, Atlanta, GA BACKGROUND: HIV-infected women are at increased risk for HPV-associated cervical carcinoma. This study was done to assess the effect of HAART on HPV load in vaginal secretions. METHODS: Plasma HIV-1 RNA and vaginal lavage HPV DNA specimens were obtained at 345 visits (range 3-17) from 44 HIV-infected women. At each vis |
| 120 | Effect of Nevirapine (NVP) for Perinatal HIV Prevention Appears Greatest Among Women with Most Advanced Disease: Subgroup Analyses of HIVNET 012. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 120 M. G. Fowler*1, A. Mwatha2, L. Guay3, P. Musoke4, F. Mmiro4, T. Fleming5, and J.B. Jackson3 for the HIVNET 012 Study Team Transmission was significantly lower among Ugandan women receiving NVP compared to ZDV overall and for those with the most severe immune suppression and highest viral burden. These data support the efficacy of the simple NVP two dose peripartum regimen even among women with the most advanced HIV disease. |
| 121 | Early HCV Viral Dynamics in HIV/HCV-Infected Patients on HCV Treatment. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 121 Torriani FJ, Ribeiro RM, Gilbert TL, Schrenk UM, Clauson M, Pacheco DM, Perelson AS; Univ. of California, San Diego BACKGROUND: On daily interferon (5-15 mIU), plasma HCV RNA follows a biphasic viral decay curve, with a HCV viral half-life of 2.7 hours. If HCV clearance is slower in HIV/HCV patients, longer treatment may be required to ensure sustained response rates similar to those seen in HCV monoinfection. We characterized the e |
| 122 | HCV RNA Kinetic Response to PEG-Interferon and Ribavirin in HIV Co-Infected Patients. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 122 K. E. Sherman*1, P. Horn1, S. Rouster1, M. Peters2, M. Koziel3, and R. Chung 4 for the ACTG 5071/5091 Study Group PEG-IFN + ribavirin, compared to standard interferon + ribavirin, appears to increase phase 1 HCV viral clearance, which has been attributed to direct inhibition of viral replication and/or release. This may contribute to more rapid time to estimated complete viral clearance predicted by phase II kinetics. A slightly delayed onset of action is observed in the PEG-IFN treatment group, which may reflect altered absorption or release from pro-drug, but this does not appear to be detrimental to antiviral efficacy at 48 hours. |
| 123 | Adefovir Dipivoxil 10 mg Suppresses HBV Viral Replication in HIV/HBV Co-Infected Patients with Lamivudine Resistant HBV. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 123 Benhamou Y, Bochet M, Thibault V, Calvez V, Fievet MH, Sullivan M, Brosgart C, Namini H, Poynard T, Katlama C; GH Pitie-Salpetriere, Paris, France BACKGROUND: Lamivudine resistance (LAM(R)) has been associated with progressive liver disease and hepatic decompensation. The incidence of LAM(R) increases with increasing duration of treatment: after 4 years, approximately 90% of HIV/HBV co-infected patients are LAM(R). Adefovir dipivoxil (ADV) has potent activity aga |
| 124 | Anti-HBV Activity of Tenofovir Disoproxil Fumarate (TDF) in Lamivudine (LAM) Experienced HIV/HBV Co-Infected. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 124 Cooper D, Cheng A, Coakley D, Sayre J, Zhong L, Chen SS, Westland C, Miller M, Brosgart C, The 907 Study Team; NCHECR, Univ. of New South Wales, Australia BACKGROUND: LAM resistance to HBV occurs in approximately 15-32% of both HBV and HIV/HBV co-infected patients after 1 year of LAM therapy. TDF has potent in vivo and in vitro activity against both wild-type and LAM resistant HBV. To evaluate the safety and efficacy of TDF 300 mg in the treatment of patients with HIV/HB |
| 125 | Antiretroviral Therapy and Mortality among HIV-Positive Liver Transplant Recipients. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 125 Ragni M, Neff G, Heaton N, Roland M, Stock P, Humar A, Fung J; Univ. of Pittsburgh, PA BACKGROUND: Despite growing evidence that highly active antiretroviral therapy (HAART) enhances survival among human immunodeficiency virus (HIV)-positive subjects with end-stage liver disease (ESLD) who undergo liver transplantation (OLTX), some subjects experience early mortality. Because past OLTX mortality was asso |
| 126 | Pharmacokinetics of Once-Daily vs Twice-Daily Kaletra (Lopinavir/Ritonavir) in HIV+ Subjects Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 126 Bertz R, Foit C, Ye X, Manning L, Bernstein B, Renz C, Hsu A, King M, Granneman GR, Sun E; Abbott Labs., Abbott Park, IL BACKGROUND: Kaletra is a coformulation of lopinavir (LPV), an HIV protease inhibitor, and ritonavir (r), which provides enhanced LPV plasma conc. A LPV/r dose of 400/100 mg BID yields a LPV mean inhibitory quotient (I |
| 127 | Reduced Accumulation of Ritonavir and Saquinavir in PBMCs in Vivo is Associated with Increased P-gp and MRP1 Expression in HIV-Infected Individuals Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 127 Meaden E, Hoggard P, Newton P, Tjia JF, Aldam D, Cornforth D, Lloyd J, Smith A, Williams I, Beeching N, Stockwell E, Wilkins E, Carey P, Back D, Khoo S; Univ. of Liverpool BACKGROUND: Increased expression of multidrug efflux transporters has been implicated as a potential mechanism for decreased drug availability at intracellular sites that provide sanctuary for HIV. As HIV protease inhibitors are substrates for the efflux transporters P-glycoprotein (P-gp) and MRP1, we investigated whet |
| 128 | The Normalized Inhibitory Quotient (NIQ) of Lopinavir Is Predictive of Viral Load Response over 48 Weeks in a Cohort of Highly Experienced HIV-1-Infected Individuals Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 128 Castagna A, Danise A, Hasson H, Boeri E, Lazzarin A, Peeters M, Piscitelli S, Hoetelmans R; Hosp. San Raffaele, Milan, Italy BACKGROUND: Resistance testing provides information on the susceptibility of a patient s HIV-1 to antiretrovirals. However, it does not incorporate exposure to drugs needed to suppress replication. In this study we examined the relationship between viral susceptibility, drug exposure, and the combination of these, the |
| 129 | The Inhibitory Quotient (IQ) for Saquinavir (SQV) Predicts Virologic Response to Salvage Therapy. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 129 Fletcher CV, Cheng H, Fiscus SA, Swanstrom R, Hellmann NS, Haubrich R, Katzenstein D, Gulick R, The ACTG 359 Team; Univ. of Minnesota, Minneapolis BACKGROUND: ACTG 359 was a controlled study of SQV (soft gel) with ritonavir (RTV) or nelfinavir (NFV), and delavirdine (DLV), adefovir (ADV), or both. In this report, relationships between SQV IQ and virologic response were investigated in a pharmacology substudy. |
| 130 | The Use of Virtual Inhibitory Quotient (VIQ) in Antiretroviral (ART)-Experienced Patients Taking Amprenavir/Lopinavir Combinations Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 130 Phillips E, Tseng A, Walker S, Loutfy M, Walmsley S, Tailor S, Harrigan PR; Sunnybrook & Women's Coll. Hlth. Sci. Ctr. BACKGROUND: There is increasing evidence to suggest that drug levels of protease inhibitors (Pis) correlate with virologic outcome. The appropriate application of VIQ (C min/(virtual phenotype [VP] fold change x protein corrected EC (50) for wildtype) has not been defined. VIQ may be a more useful measurement than drug |
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| 131-M | SIVcpz Infection in Wild Chimpanzees Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 131-M Santiago M, Rodenburg C, Kamenya S, Bibollet-Ruche F, Gao F, Bailes E, Fahey B, Muller M, McClure H, Heeney J, Pusey A, Collins D, Boesch C, Wrangham R, Goodall J, Sharp P, Shaw G, Hahn B; Univ. of Alabama, Birmingham BACKGROUND: West-central African chimpanzees (Pan troglodytes troglodytes) are known to harbor strains of SIVcpz that are closely related to all 3 groups of HIV-1 (M, N, and O) and have thus been implicated as a reservoir for human infection. Yet, because all SIVcpz strains identified to date have been derived from cap |
| 132-M | Molecular and Biological Characterization of SIVcpzGab2. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 132-M Bibollet-Ruche F, Santiago ML, Decker J, Bailes E, Gao F, Saragosti S, McClure H, Delaporte E, Peeters M, Sharp P, Shaw G, Hahn B; Univ. of Alabama, Birmingham BACKGROUND: SIVcpzGab2 was originally detected in a wild-born chimpanzee from Gabon by serological analyses, but repeated culture attempts failed to yield a replicating virus isolate. To characterize this potentially interesting SIVcpz strain, we amplified full-length SIVcpzGAB2 genomes using an approach that produced |
| 133-M | New Divergent Simian Immunodeficiency Viruses from Captive Sooty Mangabeys -- Their Non-Invasive Detection Is Dependent on Plasma Viral Loads Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 133-M Ling B, Santiago M, Gormus B, Hahn B, Marx P; Aaron Diamond AIDS Res. Ctr., Rockefeller Univ., New York, NY BACKGROUND: Simian immunodeficiency virus (SIV) is found as a natural infection of sooty mangabeys. SIVsm is of interest because it is the ancestral virus of HIV-2 that emerged in West Africa through cross-species transmission. To investigate the diversity and evolution of SIVsm in this endangered species, it would be |
| 134-M | Simian Retrovirus Infections in Persons Occupationally Exposed to Non-Human Primates. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 134-M Switzer WM, Shanmugam V, Bhullar V, Yee JA, Lerche N, Boneva RS, Chapman LE, Folks TM, Heneine W; CDC, Atlanta, GA BACKGROUND: Current evidence suggests that HIV-1 and HIV-2 have originated from cross species infections of simian immunodeficiency virus (SIV) from non-human primates. Humans remain at risk of zoonotic infections with SIV or other simian retroviruses endemic among non-human primates. To better assess these risks we st |
| 135-M | Comparing Inter-Subtype HIV-1 Recombinants Generated in Vitro to Those Found in Vivo Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 135-M Baird H, Quinones-Mateu M, Arts E; Case Western Reserve Univ., Cleveland, OH BACKGROUND: Increased prevalence of inter-subtype HIV-1 recombinants (ISRs) is shaping HIV-1 evolution throughout the world and will have an impact on both therapeutic and vaccine strategies. This study was designed to generate and compare ISRs in vitro to those isolated from HIV-infected individuals throughout the wor |
| 136-M | Evolution of HIV-1 Infection and Co-Receptor Usage in Central African Republic Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 136-M Begaud E, Feindirongai G, Versmisse P, Ipero J, Leal J, Germani Y, Morvan J, Muller-Trutwin M, Pancino G, Barre-Sinoussi F; Pasteur Inst., Bangui, Central African Republic BACKGROUND: A switch from R5 to X4 tropic HIV-1 has been associated with progression to AIDS in Caucasian individuals infected mainly by HIV-1 subtype B. It has been also suggested that in Africa the progression to AIDS in HIV-1-infected individuals is more rapid than in Europe and the United States . We report here |
| 137-M | Presence of CXCR4-Tropic Viruses among Subtype C HIV-Infected Individuals. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 137-M Johnston E, Mutetwa S, Zijenah L, von Lieven A, Israelski D, Kittinunvorakoon C, Kantor R, Katzenstein D; Stanford Univ., Palo Alto, CA BACKGROUND: Subtype C HIV viruses usually use CCR5 as a co-receptor. We have characterized co-receptor usage in subtype C viruses and the frequency of syncytium-inducing (SI) viruses among individuals infected with subtype C HIV and exposed to antiretroviral therapy (ARV). METHODS: PBMCs were isolated from 38 consecuti |
| 138-M | HIV Evolution Is Largely Consistent with a Molecular Clock Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 138-M Nickle DC, Liu Y, Learn GH Jr, Shiner D, Mullins J; Univ. of Washington, Seattle BACKGROUND: A recent manuscript by Posada and Crandall calls into doubt the validity of a molecular clock in HIV-1. We believe their conclusion to be erroneous since they tested the molecular clock hypothesis with serially sampled data (specifically, samples they used in their analysis were taken 5 years apart). We wou |
| 139-M | Assessment of the Contributions of Vpr-Mediated G2/M Arrest and Nuclear Import to HIV-1 Replication in Culture Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 139-M Sanchez PV, Malim MH; Univ. of Pennsylvania, Philadelphia BACKGROUND: The documented roles of Vpr in HIV-1 replication include the regulation of pre-integration complex nuclear import, the induction of apoptosis as a factor in viral pathogenesis, and the arrest of infected cells at the G2/M phase of the cell cycle as a means of upregulating the viral LTR promoter. Because the |
| 140-M | Cytoplasmic-Nuclear Shuffling of HIV-1 Vpr and Its Effect on Integrity of the Nuclear Envelope Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 140-M Elder RT, Yu M, Hou J, Chen M, Priet S, Sheerer A, Chiu K, Sire J, Zhao Y; Northwestern Univ. Med. Sch., Chicago, IL BACKGROUND: Vpr plays an important role in transport of the viral pre-integration complex into the nucleus. Consistent with this role, Vpr contains nuclear localization signals and has also recently been shown to be involved in cytoplasmic-nuclear shuffling. METHODS: We have made a number of observations about the dyna |
| 141-M | Involvement of HIV Vpr Protein in G2/M Arrest through Interaction with 14-3-3 Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 141-M M. Tsopanomichalou*1, T. Kino2, A. Gragerov1, G. Ilyina-Gragerova1, G. P. Chrousos2, and G. N. Pavlakis1 Our data show interaction of 14-3-3 with Vpr both in vitro and in vivo. The model supported by these data is that interaction of Vpr to 14-3-3 results in the export of Cdc25C from the nucleus, leading to the G2/M arrest observed in the presence of Vpr. |
| 142-M | Multicopy Suppressors and Enhancers of Cell Cycle G2 Arrest Induced by HIV-1 Viral Protein R (Vpr) in Fission Yeast (Schizosaccharomyces Pombe) Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 142-M Z. Benko*, R. T. Elder, S. Innis, M. Yu, M. Chen, and Y. Zhao Characterization of these Vpr suppressors and enhancers will allow us to elucidate further the pathway(s) for the G2 arrest induced by Vpr. |
| 143-M | Functional Significance of Naturally Occurring Mutants in HIV-1 Vpr Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 143-M Tungaturthi PK, Singh SP, Cartas M, Tomkowicz B, Ayyavoo V, Mahalingam S, Murali R, Srinivasan A; Thomas Jefferson Univ., Philadelphia, PA BACKGROUND: HIV-1 Vpr is a 96-amino-acid, 14-kDa protein expressed in infected cells in a Rev-dependent manner and packaged into virions through interaction with the p6 region of the p55gag precursor. It is a pleiotropic protein involved in cell cycle arrest at G2, nuclear localization, transport of the preintegration |
| 144-M | Physical and Functional Interaction between Viral Protein R and p21WAFI. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 144-M Sawaya BE, Singh SP, Khalili K, Clavo A, Srinivasan A, Amini S; Temple Univ., Philadelphia, PA BACKGROUND: HIV-1 infection is often associated with the central nervous system (CNS) dysfunction. The viral protein R (Vpr) is a virion-associated protein, encoded by HIV-1 genome, with multiple biological functions. It has been shown by several laboratories including ours that Vpr binds to a number of viral proteins |
| 145-M | HIV-1 Vpr Causes Cell Cycle Arrest via a Pathway Involving p38 MAP Kinase and ATR Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 145-M Roshal M, Zhu Y, Planelles V; Univ. of Rochester, NY BACKGROUND: The HIV-1 viral protein R (Vpr) causes cell cycle arrest and apoptosis in dividing cells. The cellular pathway that leads to Vpr-induced arrest and apoptosis is active in all tested neoplastic cell lines and is independent of p53 status. Several recent reports have indicated that the effects of Vpr may be s |
| 146-M | Vpr Mutation R77Q Is Associated with Long-Term Non-Progressive HIV-Infection and an Impaired Ability to Induce T-Cell Depletion in Vivo Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 146-M J. Lum*1, O. J. Cohen2, D. H. Lynch4, A. A. Pilon1, J. E. Kim2, Z. Chen3, M. Montpetit3, J. Sanchez-Dardon1, N. Hawley-Foss1, G. Garber1, and A. D. Badley1 8/10 patients in our LTNP cohort have an R77Q mutation in Vpr, a mutation frequency that is similar to other cohorts of LTNP. In vitro, R77Q induced lower levels of apoptosis and less caspase activation than with WT Vpr. Mice injected with R77Q vpr had significantly less T-cell depletion and local tissue damage compared to mice injected with WT vpr. Therefore, R77Q in Vpr may represent an additional mechanism of LTNP. |
| 147-M | Visualizing Intracellular HIV Reverse Transcription Complexes by Immunofluorescent and Electron Microscopy Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 147-M D. McDonald*1, M. Vodicka2, G. Lucero3, T. M. Svitkina4, G. G. Borisy4, M. Emerman2, and T. J. Hope1 Analysis of the early events in HIV infection by this means has allowed us to identify interactions between HIV and the cell cytoskeleton as well as to define virion protein composition during reverse transcription. The presence of p24 in RTCs has not been previously reported, and may mark an early stage RTC, such as one which has not yet completed an uncoating event. EM analysis provides the first examples of intracellular virion structure, and supports the hypothesis that RTCs associate with the cellular microtubule machinery. |
| 148-M | tRNA Primer Sequences Required for Replication of Recombinant SIV Containing HIV-1 Reverse Transcriptase Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 148-M Alexander L, Soderberg K; Yale Univ., New Haven, CT BACKGROUND: A recombinant SIV with reverse transcriptase sequences from HIV-1 strain HXB2 (RT/SHIV) was constructed to develop a model to test the effects of RT inhibitors in experimentally infected monkeys. This recombinant was severely impaired in replication. METHODS: We sequenced RT/SHIV that grew to detectable lev |
| 149-M | Effects of 69S-XX Finger Insertion Mutations in HIV-1 Reverse Transcriptase on Nucleotide-Dependent Removal of ddA Monophosphate from Blocked DNA Chains Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 149-M Meyer P, Lennerstrand J, Matsuura S, Larder B, Scott W; Univ. of Miami, FL BACKGROUND: Resistance to multiple nucleoside analogues can be associated with a 69S mutation in combination with a dipeptide insertion between amino acids 69 and 70 (69S-XX mutants) in HIV-1 reverse transcriptase (RT). For high-level resistance, these so-called finger insertion mutations are generally present together |
| 150-M | Mutations in the p51-RNase H Protease Cleavage Junction Effects Intravirion Stability of HIV-1 Reverse Transcriptase Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 150-M Abram M, Arion D, Sluis-Cremer N, Parniak M; Univ. of Pittsburgh Sch. of Med., PA BACKGROUND: The gene for HIV-1 reverse transcriptase (RT) encodes a 66-kDa protein, but mature HIV-1 RT exists as a p66/51 heterodimer. The p51 subunit is derived from the full length p160(Gag-Pol) polyprotein or previously excised 66 kDa RT subunit during virus assembly and/or maturation. Nonetheless, recombinant p66/ |
| 151-M | The Tat Protein of HIV-1 can Promote the Annealing of tRNALys3 onto the Primer-Binding Site (PBS) and can also Promote the First Strand Transfer in Reverse Transcription. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 151-M Wainberg MA, Liang C, Guo X, Kameoka M; McGill Univ. AIDS Ctr., Montreal, QC, Canada BACKGROUND: Tat has been proposed to play a role in regulation of reverse transcription. We previously demonstrated that wild-type Tat can augment viral infectivity by suppressing the reverse transcriptase (RT) reaction at late stages of the viral life cycle in order to prevent the premature synthesis of potentially de |
| 152-M | Regulation of the HIV-1 Pre-Integration Complex (PIC) in Primary Human Lymphocytes Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 152-M A. Brooun1, D. Chinnasamy2, V. Snarsky1, C. Spina1, D. D. Richman1, F. Candotti2, and R. Kornbluth*1 These results are the first measurements of PIC formation in primary cells, and are made possible by a new, sensitive, PCR-based assay for HIV integration. The studies indicate that an inactive "pro-preintegration complex" or "pro-PIC" is formed in resting T cells as the physical embodiment of preintegration latency. The maturation of the pro-PIC to an integration-competent PIC provides an additional therapeutic target for drug discovery. |
| 153-M | Late HIV-1 Reverse Transcripts Accumulate Stably within Resting CD4(+) T Cells Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 153-M Swiggard W, O'Doherty U, McGain D, Jeyakumar D, Malim M; Univ. of Pennsylvania, Philadelphia BACKGROUND: Most of the virus that accumulates in HIV-infected individuals despite successful HAART is within resting CD4(+) T cells, including both naïve and memory cells. The mechanism(s) whereby viral latency is established in these cells is not known in detail, although it is clear that reverse transcription is ver |
| 154-M | Differential Interaction with Actin by HIV-1 Gag and Matrix Protein Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 154-M Gomez C, Hope T; Univ. of Illinois, Chicago BACKGROUND: Human immunodeficiency virus type 1 matrix protein has important functions in both viral assembly and entry. Matrix is critical for the targeting of the Gag polyprotein to the plasma membrane and for the incorporation of the viral envelope (Env) glycoproteins into budding virions. Other studies suggest that |
| 155-M | Investigating Retroviral Trafficking Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 155-M Vodicka M, Imakura M, McDonald D, Hope TJ, Emerman M; Fred Hutchinson Cancer Res. Ctr., Seattle, WA BACKGROUND: Lentiviruses, such as HIV, differ from the oncogenic retroviruses in several ways. Lentiviruses infect non-dividing cell types while oncogenic viral infection is limited to proliferating cells. Lentiviral infection tends to be acute and persistent while oncogenic viral infection tends to be chronic and late |
| 156-M | A Sensitive, Quantitative Assay for HIV-1 Integration Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 156-M O'Doherty U, Swiggard W, Jeyakumar D, McGain D, Malim M; Univ. of Pennsylvania, Philadelphia BACKGROUND: In resting CD4 (+) T cells, HIV-1 establishes a nonproductive or latent form of infection that has been implicated in the accumulation of reservoirs of treatment-resistant virus in HIV-infected patients. Such reservoirs accumulate in the presence or absence of successful HAART combination |
| 157-M | Analysis of 2-LTR Circle Stability and Gene Expression in Primary Human Macrophages Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 157-M Cunningham T, Mediavilla J, Pope M, Muesing M; Aaron Diamond AIDS Res. Ctr., Rockefeller Univ., and Population Council, Ctr. for BioMed. Res., New York, NY BACKGROUND: During human immunodeficiency virus type-1 (HIV-1) infection, the viral enzyme integrase catalyzes both the 3 processing and strand-transfer reactions, both of which are required for integration of retroviral DNA into the host chromosome. When the ability of the integrase to catalyze the strand transfer rea |
| 158-M | HIV-1 Extrachromosomal Circular DNA is Long-Lived in Non-Dividing Cells and Proteins Expressed from the Circles May Play a Role in Viral Pathogenesis Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 158-M Gillim L, Cara A, Klotman ME; Mount Sinai Sch. of Med., New York, NY BACKGROUND: Recent findings have demonstrated that HIV-1-infected patients on highly active anti-retroviral therapy (HAART) with undetectable levels of viral RNA ( |
| 159-M | Longitudinal Studies of 2-LTR Circles in Patients on CART. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 159-M J. Morlese*, I. Teo, J. W. Choi, B. Gazzard, and S. Shaunak The median half-life of 2-LTR circles is 118 hours in vivo and < 24 hours in vitro. Most patients with sustained plasma HIV-1 RNA of < 50 copies/mL have persistent 2-LTR circles in their PBMCs. With < 30 circles/106 PBMCs there is little fluctuation over time. The reservoir of ongoing viral replication in such patients is therefore stable and a single point determination of circles reliably indicates activity in the reservoir. In patients with > 30 circles/106 PBMCs there is more fluctuation in copy number with time. This may reflect an unstable reservoir. Regular 2-LTR circle monitoring is therefore a useful clinical indicator of whether the reservoir of ongoing viral replication in patients on CART is stable or enlarging. |
| 160-M | Characterization of the Pre-Integration State of HIV-1 Latency Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 160-M Pierson T, Zhou Y, Kieffer T, Ruff C, Siliciano R; Johns Hopkins Sch. of Med., Baltimore, MD BACKGROUND: The infection of resting CD4+ T cells by HIV-1 is not productive due to a block upstream of the integration of the viral genome into the host cell chromosome. However, stimulation of an infected resting T cell can overcome this block and allow for the production of progeny virions. In this study we sought t |
| 161-M | Exposing the Latent Reservoir of Human Immunodeficiency Virus Type-1 (HIV-1) via Blockade of Host Repressors. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 161-M Margolis DM, He G, Ylisastigui L, Rucker VC, Dervan PB; Univ. of Texas Southwestern Med. Ctr., Dallas BACKGROUND: The latent reservoir of HIV-1 within resting CD4+ T cells is an obstacle to the long-term treatment of HIV infection. Without activation, the HIV-1 long terminal repeat (LTR) remains quiescent within these cells. The host factors LSF and YY1 repress the LTR by recruiting histone deacetylase 1 (HDAC1) to the |
| 162-M | A Dual Role for Leader Sequences Downstream of the SIV Stem-Loop 1 in RNA Packaging and Dimerization of Simian Immunodeficiency Virus RNA Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 162-M Whitney JB, Olivera M, Spira B, Guan Y, Wainberg MA; McGill AIDS Ctr., Montreal, QC, Canada BACKGROUND: The virion-associated genomes of both HIV-1 and SIV consist of a non-covalently linked dimeric structure that is comprised of 2 full-length genome copies. The selective enrichment of retroviral RNA into nascent virions has been studied intensively in HIV-1; yet precise identification of cis-acting determina |
| 163-M | Identification of Novel Sequences Involved in HIV-1 Genomic RNA Dimerization Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 163-M Russell RS, Hu J, Wainberg MA, Liang C; McGill AIDS Ctr., Lady Davis Inst., Jewish Gen. Hosp., Montreal, QC, Canada BACKGROUND: HIV-1, like all retroviruses, packages 2 copies of its RNA genome in dimeric form, however, the exact mechanism and timing of this process is not completely known. The dimerization initiation site (DIS) in HIV-1 has been mapped to a stem-loop structure (SL1), yet HIV-1 mutant viruses with disruptions in SL1 |
| 164-M | Transduction of Cellular Sequence by Human Immunodeficiency Virus Type 1. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 164-M Sun G, O'Neil PK, Ron Y, Preston BD, Dougherty JP; Univ. of Med., and Dentistry, New Jersey-Robert Wood Johnson Med. Sch., Piscataway BACKGROUND: It is well established that oncoretroviruses can transduce cellular genes. Acutely transforming retroviruses contain oncogenes that are derived from cellular proto-oncogenes. The products of proto-oncogenes normally function in signal transduction and cell cycle regulation. However, it has not been reported |
| 165-M | HIV-1 Protease Dimerization and Virus Assembly Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 165-M Pettit S, Everitt L, Choudhury S, Kaplan AH; Univ. of North Carolina, Chapel Hill BACKGROUND: Dimerization of the HIV protease is an essential step in virus replication. The active enzyme is a homodimer, held together in large part by 8 residues in each monomer that form a 4-stranded B-sheet. METHODS: To identify the role played by individual residues in dimer formation and to characterize the contr |
| 166-M | Temporal Modulation of Monocyte-Derived Macrophage Gene Expression During HIV-1 Infection Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 166-M Ottones F, Royer C, Corbeil J; Univ. of California, San Diego BACKGROUND: Macrophages may play a crucial role in both immune suppression and the formation of viral reservoirs during HIV infection. To better understand the role of macrophages in HIV infection, we used oligonucleotide probe arrays to quantify host gene expression during HIV-1 infection. METHODS: We analyzed the tem |
| 167-M | HIV-1 Nef-Mediated Recruitment of Adaptor Protein Complexes. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 167-M Hitchin D, Janvier K, Craig H, Coleman S, Benichou S, Guatelli J; Univ. of California, San Diego Med. BACKGROUND: HIV-1 Nef modulates intracellular protein trafficking to down-regulate CD4, enhance viral infectivity, and inhibit antigen presentation by class I MHC. Interactions between Nef and the cellular proteins that coat the cytoplasmic face of vesicles involved in membrane transport appear essential to these effec |
| 168-M | Gene Expression Studies of in Vitro HIV-1 Infection: HIV-1 Activates Transcription of the Sterol Biosynthesis Pathway. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 168-M van't Wout A, Lehrman G, Mikheeva S, O'Keeffe G, Geiss G, Bumgarner R, Mullins J; Univ. of Washington, Seattle BACKGROUND: HIV-1 requires host cell factors to survive and replicate. In addition, HIV-1 needs to interfere with cellular pathways aimed at destroying viral replication. Multiple cellular pathways are likely to be affected at various times during infection and by different molecular mechanisms. METHODS: We use high-de |
| 169-M | Identification of a Recombination Hot Spot in HIV-1 Gag Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 169-M Dykes C, Planelles V, Zhu Y, Demeter LM; Univ. of Rochester Sch. of Med. and Dentistry, NY BACKGROUND: Reverse transcriptase-mediated recombination and mutation contribute to retroviral diversity. We hypothesized that certain regions, or hot spots, would undergo recombination more frequently than others. Under circumstances in which the effective replicating pool of HIV is limited, such hot spots could influ |
| 170-M | Differences in Genetic Recombination during HIV-1 and MLV Replication. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 170-M Onafuwa A, An W, Robson N, Telesnitsky A; Univ. of Michigan Med. Sch., Ann Arbor BACKGROUND: Previous reports suggest that the HIV-1 recombination rate is higher than that of murine leukemia virus (MLV), but the reasons for this have not been well described. This study addresses the question of whether the differences in recombination rates in these 2 retroviruses arise from differences in template |
| 171-M | A Role for PI3-Kinase Signaling during HIV Infection of Primary CD4+ T Lymphocytes and Macrophages. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. Francois F, Klotman ME; Mt. Sinai Sch. of Med., New York, NY BACKGROUND: HIV gp120-induced signal transduction may affect the efficiency of virus entry and infection and can have important consequences for target cell function. The phosphatidylinositol 3-kinase (PI3-kinase) pathway regulates a diverse range of cellular functions such as cytoskeletal rearrangement, cell prolifera |
| 172-M | Apoptosis Signal to CD4+ T Cells in HIV-1 Infected Hu-PBL-SCID Mice Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 172-M Koyanagi Y, Miura Y; Tohoku Univ. Graduate Sch. of Med., Sendai, Japan BACKGROUND: HIV infection induces gradual loss of CD4+ T cells leading to AIDS but the mechanisms of increased destruction of CD4+ T cells in vivo remain unclear. To explore the pathological processes occurring in the organs in HIV-infected humans, it is helpful to develop an appropriate animal model. METHODS: Human PB |
| 173-M | Human T-Cell Leukemia Virus Type-I Buds from Lipid Rafts Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 173-M Niyogi K, Hildreth J; Johns Hopkins Univ. Sch. of Med., Baltimore, MD BACKGROUND: We have previously shown that lipid rafts are implicated in human T-cell leukemia virus type I (HTLV-1)-induced syncytium formation. Lipid rafts are sites on the cell plasma membrane enriched in cholesterol, sphingolipids, and glycosylphosphatidylinositol (GPI)-anchored proteins. We have previously shown th |
| 174-M | C-Peptide Inhibitors of HIV-1 Entry Do not Disrupt Formation of a 6-Helix Bundle Structure in gp41 Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 174-M N. Kilgore, K. Salzwedel, G. Allaway, and C. Wild* These results confirm the observation that sCD4-induced conformational changes in gp120 mediate the interaction of gp41 helical domains leading to formation of the 6-helix bundle. Importantly, they extend earlier results to include the primary virus isolate ADA suggesting that sCD4-induced changes in envelope structure mimic those that occur during natural infection. We also show that high concentrations of C-peptide inhibitors have no effect on the formation of the 6-helix bundle as measured by binding of antibodies specific for this structure. This result suggests that the antiviral activity of DP-178 and similar peptides does not result from a dominant-negative interaction with the N-helical domain gp41. |
| 175-M | The Role of Cell Surface Heparan Sulfate Proteoglycans (HSPGs) in HIV-1 Viral Assembly and HIV-1 Tat Cellular Uptake. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 175-M Argyris EG, Meyer ME, Williams KJ, Pomerantz RJ; Jefferson Med. Coll., Thomas Jefferson Univ., Philadelphia, PA BACKGROUND: Recent studies have demonstrated the significance of cell surface HSPGs in HIV-1 infection, as well as the cellular uptake of Tat, the transactivator protein of HIV-1. In this study we examined: The hypothesis that HIV-1 in the process of viral budding incorporates HSPG molecules; and the role of perlecan, |
| 176-M | Role of the Viral Envelope-Matrix Complex and Host Cytoskeleton in the Selective Incorporation of Host ICAM-1 Protein into HIV-1. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 176-M Beausejour Y, Tremblay MJ; Univ. Laval, Ste-Foy, QC, Canada BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) acquires a vast array of host cell proteins when the budding process takes place in infected cells. However, the nature of factor(s) responsible for the incorporation of foreign constituents remains a matter of speculation. It has been postulated that a physical i |
| 177-M | Incorporation of Host CD80 (B7.1) and CD86 (B7.2) Glycoproteins into HIV-1 Increases Viral Infectivity in Primary Human Mononuclear Cells. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 177-M Bounou S, Giguere JF, Tremblay MJ; Univ. of Laval, Ste-Foy, QC, Canada BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) acquires several host cell membrane proteins during the budding process. It was demonstrated that the attachment process is accentuated by supplementary interactions between virion-anchored host molecules and their cognate ligands. Furthermore the enhancement of t |
| 178-M | Low Quantity of SU on HIV Is Due to Low Incorporation of Envelope Glycoproteins and not to Shedding. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 178-M Chertova E, Bess J, Crise B, Sowder R II, Schaden T, Hilburn J, Hoxie J, Henderson L, Arthur LO; SAIC, Frederick, MD BACKGROUND: Our program has focused on the design and synthesis of whole inactivated virion particle vaccines, specifically, using methods to irreversibly inactivate live virus while retaining native and functional envelope (Env) proteins. To study the contribution of SU density to the efficacy of the vaccine we focus |
| 179-M | Poor Fitness of Subtype C HIV-1 Isolates Is Controlled by the Efficiency of Host Cell Entry and Maps to the Env Gene Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 179-M Arts E, Ball S, Ahabra A, Marozsan A; Case Western Reserve Univ., Cleveland, OH BACKGROUND: Our primary objective is to investigate possible differences in subtype fitness, knowing that HIV-1 fitness has a significant impact on disease progression. METHODS: We have recently established a dual virus competition assay to measure the relative fitness of any 2 HIV-1 isolates ex vivo. This assay involv |
| 180-M | Involvement of the Bridging Sheet of HIV-1 Envelope in Co-Receptor Interactions Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 180-M Biscone M, Reeves J, Baribaud F, Baik S, Doms RW; Univ. of Pennsylvania, Philadelphia BACKGROUND: The bridging sheet domain in HIV-1 gp120 is involved in CCR5 binding. This region is composed of amino acids that are highly conserved across all known HIV-1 strains. Hence, the bridging sheet may be involved in binding to other HIV-1 co-receptors and may govern co-receptor affinity. Therefore, the interact |
| 181-M | Gp41-Mediated Apoptosis is Independent of HIV Co-Receptor Use but Requires Proper Presentation by gp120 Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 181-M Blanco J, Barretina J, Clotet B, Este JA; Fndn. irsiCaixa, Barcelona, Spain BACKGROUND: Cell-surface HIV envelope (Env) from X4 isolates mediates the death of single CD4 T cells by a gp41-dependent mechanism that involves lipid but not cytoplasm mixing between Env+ cells and CD4+ cells. While X4 Env appears to be highly pathogenic by both syncytium formation and the induction of single cell ki |
| 182-M | Early SIVsm Re-Isolates Show Broad Co-Receptor Use in Comparison with Late Re-Isolates Obtained from Experimentally Infected Cynomolgus Macaques Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 182-M Vodros D, Thorstensson R, Biberfeld G, Schols D, De Clercq E, Fenyo EM; Karolinska Inst., Stockholm, Sweden BACKGROUND: SIV infection in monkeys is a model for HIV infection in humans. This model allows us to study very early events following infection. It is therefore important to compare the biological features of the 2 systems. Here we describe the co-receptor use of sequential isolates from 8 macaques with fast or slow d |
| 183-M | Contrasting Dependence on CCR5 Determinants by R5 and R5X4 Quasi-Species within 89.6 Primary Isolate Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 183-M Singh A, Collman RG; Univ. of Pennsylvania, Philadelphia BACKGROUND: Dual-tropic R5X4 HIV-1 species bridge the transition from M-tropic R5 to T-tropic X4 variants by retaining the ability to use highly divergent N-terminal domain of CCR5 and acquiring the ability to use relatively conserved extracellular loops of CXCR4. Our recent studies have revealed the presence of distin |
| 184-M | Examination of HIV-1 Resistance to RANTES Derivatives through the Use of a Unique Recombinant Envelope Pseudo-Typing Method Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 184-M Marozsan A, Abraha A, Baird H, Arts E; Case Western Reserve Univ., Cleveland, OH BACKGROUND: RANTES derivatives (AOP-RANTES, NNY-RANTES, PSC-RANTES) were developed as potent inhibitors of HIV-1 replication blocking entry of CCR5-tropic (R5) isolates. Although these compounds are potent inhibitors, the extreme heterogeneity of the HIV-1 envelope glycoprotein gp120 and the variable coreceptor usage m |
| 185-M | The Cytoplasmic Domain of CCR5 Is Dispensable for Receptor Expression and for Function as HIV-1 Co-Receptor Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 185-M Pastore C, Picchio G, Galimi F, Hartley O, Offord R, Mosier D Scripps Res. Inst., La Jolla, CA BACKGROUND: The CC chemokine receptor 5 (CCR5) is the principal co-receptor for HIV-1 infection. Chemokines or their modified analogs that bind CCR5 inhibit HIV-1 infection, but the exact mechanism of this inhibition is not clear. Also, the importance of signaling through CCR5 during HIV-1 infection is not fully unders |
| 186-M | HIV-1 Env Signaling in Primary Human Macrophages through CCR5 and CXCR4: Role in HIV-1 Pathogenesis Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 186-M Del Corno M, Lee CH, Chen M, Liu QH, Freedman B, Collman RG; Univ. of Pennsylvania, Philadelphia BACKGROUND: HIV-1 uses the chemokine receptors CCR5 and CXCR4 as co-receptors for entry. Both CCR5 and CXCR4 are expressed by macrophages, which are important targets for HIV-1 in vivo and play a central role in AIDS pathogenesis including neurological disease. We previously showed that CCR5 and CXCR4 engagement by sol |
| 187-M | Mechanisms of HIV-1 Env-Activated Chemokine Receptor-Mediated Signal Transduction in Primary Human Macrophages Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 187-M Lee CH, Del Corno M, Liu QH, Freedman B, Collman RG; Univ. of Pennsylvania, Philadelphia BACKGROUND: HIV-1 uses the chemokine receptors CXCR4 and CCR5 as co-receptors for entry. Macrophages are an important target for HIV-1 in vivo, especially in the CNS, where both activation of uninfected cells as well as direct infection contribute to pathogenesis. We recently reported that CCR5 and CXCR4 engagement by |
| 188-M | Induction of Syncitia and CD4-Independent Infection of B Cells by Primary HIV-1 Isolates. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 188-M Zerhouni B, Zhang J, Saha K; Children's Res. Inst., Ohio State Univ., Columbus BACKGROUND: Although HIV-1 primarily infects CD4+ T cells, B cells also are frequently affected after infection with HIV-1. Further, previous studies have shown that B cells can be infected in vitro by HIV-1 through transient expression of CD4 or through B cells-T cells interactions. However, direct infection of B cell |
| 189-M | Structural and Functional Characterization of Human CXCR4 as a Chemokine Receptor and HIV-1 Co-Receptor by Mutagenesis and Molecular Modeling Studies. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 189-M Zhou N, Luo Z, Luo J, Liu D, Hall JW, Pomerantz RJ, Huang Z; Kimmel Cancer Ctr., Philadelphia, PA BACKGROUND: The human CXC chemokine receptor 4 (CXCR4) is a receptor for the chemokine stromal cell-derived factor (SDF-1a) and a co-receptor for the entry of specific strains of human immunodeficiency virus type I (HIV-1). CXCR4 is also recognized by an antagonistic chemokine, the viral macrophage inflammatory protein |
| 190-M | An Unusual Syncytia-Inducing HIV-1 Primary Isolate from the CNS that is Restricted to CXCR4, Replicates Efficiently in Macrophages, and Induces Neuronal Apoptosis Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 190-M Yi Y, Frank I, Sulcove J, Kolson DL, Collman RG; Univ. of Pennsylvania Sch. of Med., Philadelphia BACKGROUND: HIV-1 mainly infects macrophages/microglia in the central nervous system (CNS). Virus isolates from the CNS have generally been thought of as restricted to CCR5 usage, with a macrophage-tropic and non-syncytia-inducing (NSI) phenotype. Recently, however, we and others demonstrated that macrophages and micro |
| 191-M | Lipid Rafts and HIV Pathogenesis: Particle Cholesterol Is Required for Fusion and Entry into Host Cells Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 191-M Liao Z, Hildreth JE; Johns Hopkins Sch. of Med., Baltimore, MD BACKGROUND: Our previous studies have shown that budding of HIV-1 particles occurs at lipid rafts, where cholesterol, sphingolipids, and GPI-anchored protein are enriched. We also showed recently that removal of cholesterol from the membranes of HIV-susceptible cells renders those cells resistant to HIV infection and s |
| 192-M | R5-AIDS HIV-1 Clone Exhibits Higher CCR5 Binding Affinity than R5-Pre-AIDS Clones from the Same Patient. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 192-M Matthews A, Scoggins R, Olivieri K, Taylor J Jr, Chernauskas D, Camerini D; Univ. of Virginia, Charlottesville BACKGROUND: We recently reported that AIDS-associated R5 HIV-1 (R5-AIDS) biological clones have greater cytopathic effects on CD4+ thymocytes and replicate to higher levels than pre-AIDS R5 biological clones in SCID mice bearing human thymus liver grafts (SCID-hu mice). One possible explanation for the greater cytopath |
| 193-M | Pattern-Recognition Analysis of V3 Loop Sequences Suggests Single Amino Acid Changes Affect Co-Receptor Usage Only in a Complex Genetic Context Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 193-M Li F, Nickle D, Jensen M, van't Wout A, He H, Mullins J; Univ. of Washington, Seattle BACKGROUND: A phenotypic switch in HIV populations in vivo, from CCR5-using (R5) to CXCR4-using (X4) virus, has been noted late in infection in about half of patients examined. This outgrowth of X4 virus is has been correlated with progression to AIDS. It is thus desirable to be able to characterize the phenotypic dist |
| 194-M | Changes in the V2 Region of gp120 during the Course of SHIV(DH12R) Infection Lead to CD4-Independent Virus Entry Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 194-M Imamichi H, Imamichi T, Lane HC, Martin MA, Igarashi T; SAIC, Frederick, MD BACKGROUND: The highly pathogenic chimeric simian-human immunodeficiency virus (SHIV), SHIV(DH12R) causes a rapid and irreversible loss of CD4(+) T lymphocytes and AIDS-like symptoms. Disease progresses in 2 phases: an acute viremia phase followed by a long-lasting viremia phase. Recent data have indicated that tissue |
| 195-M | Direct Receptor Cross-Talk between CD4 and CCR5. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 195-M Staudinger R, Phogat S, Wang X, Dimitrov DS, Zolla-Pazner S; New York Univ. Sch. of Med. BACKGROUND: The chemokine receptor CCR5 acts synergistically with CD4 to allow the specific binding and entry of HIV-1. It was previously demonstrated that CD4 and CCR5 associate at the cell surface. Here we show biochemical and functional evidence for direct coupling of these 2 HIV-1 receptors with demonstration of en |
| 196-M | Amino Acid Residues Critical for LD78β (a Major Variant of Human MIP-1α) Binding to CCR5 and Inhibition of R5 HIV-1 Replication. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 196-M T. Miyakawa*1 , K. Obaru1, K. Maeda1, S. Harada1, H. Mitsuya1, and 2 The present data suggest that Asp-6, Pro-8, and Thr-9 are critical for LD78β binding to CCR5 and inhibition of R5 H-1 replication, and that LD78β binding to CCR5, regardless of affinity, is sufficient for LD78β's initial signal transduction, while the greater magnitude of binding is required for the greater anti-HIV-1 activity. The data also suggest that LD78β variants with appropriate amino acid substitution(s) such as LD78βD6A and LD78β(P8A) may serve as effective chemokine-based anti-HIV-1 therapeutics while preserving LD7. |
| 197-M | Implication of β-Chemokines MIP-1α, RANTES and MIP-1beta on the Protection From the HIV-1 Infection and Disease Progression. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 197-M C. Martínez*1, M. Plana1, A. Soriano1, F. García1, M. J. Maleno1, A. García1, J. Aróstegui1, J. Miró1, J. Del Romero2, C. Rodriguez1, J. I. Lorenzo3, J. M. Gatell1, and T. Gallart1 Our data showed that high plasmatic levels of MIP-1β seems to confer protection against HIV-1 infection. By contrast, high plasmatic levels of MIP-1α, probably reflecting an increased immune activation, could be used as a predictor of progression of HIV-1 infection. |
| 198-M | Expression of CCR5 on Dendritic Cells Is a Surrogate Marker for HIV Disease Progression. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 198-M Zheng BJ, Leung SK, Wong KH, Lee SS; The Univ. of Hong Kong, Hong Kong BACKGROUND: Chemokine receptors are the requisites for the entry of HIV into the human cells as co-receptors of CD4. The dynamics of the interaction between CD4+ T cells and dendritic cells (DC), the latter of which bearing an abundance of CCR5, is a subject deserving attention. We set out to examine the expression of |
| 199-M | Plasma SDF-1 Levels, SDF1-3A Genotype and CXCR4 Expression on T Lymphocytes and Their Impact on Resistance to HIV-1 Infection and Its Progression. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 199-M Soriano A, Martinez C, Garcia F, Plana M, Palou E, Arostegui J, Leujeune M, Joseph J, Miro J, del Romero J, Rodriguez C, Barrasa A, Lorenzo JI, Gatell JM, Gallart T; Univ. of Barcelona BACKGROUND: To study the relationship between plasma SDF-1 levels, SDF1-3 A polymorphism and CXCR4+ lymphocytes in relation to resistance/susceptibility to HIV-1 infection and its progression. METHODS: Cross-sectional study in HIV+ patients, including 82 long-term non-progressors (LTNP), in 60 highly exposed but uninfe |
| 200-M | SDF-1alpha Protection of HIV-1 Envelope Glycoprotein-Induced Apoptosis in Human B Lymphocytes via Mitochondrial Integrity. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 200-M C. Patke* and W. Shearer In HIV-1 infection, B cell apoptosis may be prevented due to a protective effect by the chemokine, SDF-1α, acting upon Bcl-2 to maintain mitochondrial integrity. |
| 201-M | Leukocyte Elastase Cleaves Stromal Cell-Derived Factor-1 (SDF-1) and CXCR4 HIV-1 Co-Receptor: Control of the Anti-VIH Activity of SDF-1 Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 201-M Valenzuela-Fernandez A, Planchenault T, Staropoli I, Baleux F, Leduc D, Le Barillec K, Chignard M, Delaunay T, Virelizier JL, Pidard D, Arenzana-Seisdedos F; Pasteur Inst., Paris BACKGROUND: CXCR4 is one of the 2 major HIV co-receptors, and its ligand SDF-1alpha owns the capacity to prevent cell infection by X4 HIV-1 strains. This function requires high affinity interaction between ligand and receptor, and involve the amino-terminal parts of the two molecules. Proteolytic modification of any of |
| 202-M | CXCR4-Triggered CD4 and CD8 T-Cell Apoptosis by HIV env Is Mediated by p38 MAP Kinase Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 202-M Villasis-Keever A, Bou G, Vanegas M, Gomez T, Vlahakis S, Paya CV; Mayo Clin., Rochester, MN BACKGROUND: Progressive depletion of CD4+ and CD8 T cells is a hallmark of HIV type-1 (HIV-1) infection. The T-tropic (X4) HIV envelope (env) triggers apoptosis of primary T cells through its co-receptor, CXCR4. However the signaling pathways whereby CXCR4 leads to T-cell death remains unknown. Herein we have elucidate |
| 203-T | T Helper Cell Induction in Patients with Primary HIV-1 Infection and Long-Term Non-Progressive Disease. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 203-T Malhotra U, Holte S, Emery S, Lee J, Marenza J, Corey L, McElrath MJ; Fred Hutchinson Cancer Res. Ctr.and Univ. of Washington, Seattle BACKGROUND: Antigen-specific CD4+ T helper (Th) cells are critical in the control of viral infections. Gag-specific CD4+ T-cell proliferative responses are detected in long-term non-progressors (LTNP) and in subjects receiving early antiretroviral treatment (ART). However, little is known about the role of Env-specific |
| 204-T | Induction and Persistence of Envelope-Specific T Helper Cells Following Acute HIV-1 Infection Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 204-T Malhotra U, Zhu T, Delpit E, Huntsberry C, Sette A, Shankarappa R, McElrath MJ; Fred Hutchinson Cancer Res. Ctr., Seattle, WA BACKGROUND: Antiretroviral therapy (ART) initiated during early infection is associated with the emergence of Gag-specific Th responses in most patients. However, Env responses are observed only sporadically. Furthermore, some subjects with Env responses during acute infection fail to maintain responses despite initiat |
| 205-T | Optimum Peptide Length for Stimulating HIV-1-Specific T-Helper Cell Clones Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 205-T Norris P, Moffett H, Cosimi L, Walker B, Rosenberg E; Massachusetts Gen. Hosp., Boston BACKGROUND: Despite growing evidence that HIV-1-specific CD4+ T helper cells play a role in the control of viremia, antigenic regions of HIV-1 recognized by T helper cells remain poorly defined. In CD8 CTL, there is often an optimal length peptide that is able to elicit immune responses from T-cell clones at substantia |
| 206-T | CD4+ T-Cell-Mediated Cytolytic Activity in HIV-1 Infection. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 206-T Norris P, Sumaroka M, Moffett H, Sykulev Y, Walker B, Rosenberg E; Massachusetts Gen. Hosp., Boston BACKGROUND: Mounting evidence suggests HIV-1 Gag-specific T helper cells contribute to effective antiviral control, but their functional characteristics remain to be defined. Elucidation of the mechanisms by which CD4+ T cells aid in viral control has implications for HIV-1 pathogenesis and vaccine design. METHODS: We |
| 207-T | HIV-1-Specific T-Helper Cell Responses in Long-Term Non-Progressors and Acute Seroconverters. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 207-T Cosimi L, Truong H, Wilkes B, Strick D, Walker B, Rosenberg E; Partners AIDS Res. Ctr., Boston BACKGROUND: There is increasing evidence that CD4+ T cells play a critical role in maintenance of virus-specific immunity. Strong HIV-specific T helper (Th) cell responses have been inversely associated with viral load, however, responses are often weak and do not approach the levels found in other chronic viral infect |
| 208-T | HIV-1 Replication in Vivo Is Associated with Suppression of HIV-1-Specific CD4+ T-Cell Proliferation but not with Loss of HIV-1-Specific IFN-gamma Producing CD4+ T Cells. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 208-T Palmer B, Boritz E, Wilson CC; Univ. of Colorado Hlth. Sci. Ctr., Denver A discordance between the frequency and proliferative capacity of HIV-1-specific Th cells in subjects with ongoing in vivo HIV-1 replication was found. These results also indicate that HIV-1 replication in vitro does not preclude HIV-1-specific proliferation but suggests that HIV-1 replication in vivo may cause persistent proliferative defects in HIV-1 specific CD4+ T cells |
| 209-T | Repertoire Diversity of HIV-1 p24-specific CD4+ T Cell Clones. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 209-T E. Boritz*1, B. Palmer1, B. Livingston2, and C. C. Wilson1 In HAART-treated subjects whose peripheral CD4+ T-cell pools were once severely depleted, the CD4(+) T cell response to HIV-1 may target a diverse array of epitopes restricted by multiple MHC class II molecules. Characterization of Th cell targets may facilitate the development of more effective HIV-1 vaccines and immune-based therapies. |
| 210-T | Large Oligoclonal CD4+ T-Cell Expansions in HIV-1-Infected Patients Persist with an Altered Surface Phenotype after 3 Years of Viral Suppression. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 210-T S. Bennett*, L. Goodwin, B. Kotzin, E. Connick, and the ACTG 315/375 Team Expansion of particular Vβ subsets during HIV-1 infection is associated with acquisition of a CD28-CD95+ phenotype, loss of chemokine receptor expression, and oligoclonality (loss of TCRβ diversity). Furthermore, the altered phenotype and restricted TCR diversity persist for up to 3 years in the absence of detectable virus. |
| 211-T | Substantial Rate of Lymphoproliferative Response to HIV-1-Specific Antigens after Prolonged Suppression of Viral Replication with HAART. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 211-T Breton G, Algara DS, Duval X, Longuet P, Ecobichon JL, Leport C, Vilde JL; Bichat Hosp. BACKGROUND: Specific lymphoproliferative response (LPR) to HIV-1 antigens is usually undetectable in HIV-infected patients with HAART. However, it is possible that such response has not been observed because of too short a duration of HAART. METHODS: We realized a transversal study of LPR to HIV-1 p24 and gp120 antigen |
| 212-T | Correlation between Frequencies of HIV-1-p24-Specific Th1 Cells (ELISPOT) and Plasma HIV-1 Viral Load in a Cohort of LT-NP and Slow Progressors Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 212-T Martinez V, Alatrakchi N, Costagliola D, Bonduelle O, Agut H, Autran B, The ALT Study Group; Hosp. Pitie-Salpetriere and Faculte de Med. Saint-Antoine, Paris, France BACKGROUND: HIV-1-specific T helper-1 cell responses have been associated with long-term-non-progression (LT-NP) in HIV infection but the correlation between frequencies of HIV-1-p24 specific Th1 cells and viral load have not yet been studied. We prospectively quantified the CD4 T cells specific for HIV-1 by using a ne |
| 213-T | Skewed Differentiation of HIV-Specific CD4 Memory Effector T Cells Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 213-T Harari A, Petitpierre S, Rizzardi GP, Pantaleo G; CHUV, Lausanne, Switzerland BACKGROUND: 4 subsets of memory CD8 T lymphocytes can be distinguished on the basis of the expression of CD45RA and of CCR7. Selective impairment of the differentiation of HIV-specific memory CD8+ T cells has been previously shown. In the present study, the lineage differentiation of memory CD4 T cells has been investi |
| 214-T | Defects in CD4+ T-Cell-Mediated B Cell Help in HIV-Infected Patients. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 214-T Moir S, Ogwaro K, Malaspina A, Ehler L, Liu S, McLaughlin M, Dybul M, Chun TW, Fauci AS; NIAID, NIH, Bethesda, MD BACKGROUND: The responsiveness of B cells to T cell-dependent antigens relies on the up-regulation of CD40 ligand (CD40L) on activated CD4+ T cells. We have shown that B-cell dysfunction in HIV-infected patients correlates with high plasma viremia. In the present study, we investigated the role of T-cell receptor-activ |
| 215-T | Anergy State of HIV-Specific CD4+ T Cells Detected by Class II Tetramers but Suppressed by Several Stimuli. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 215-T Yassine Diab B, Breton G, Younes S, Connors M, Lainesse M, Bernard NF, MacDonald K, Legault M, Routy JP, Sekaly RP; Univ. of Montreal, QC, Canada BACKGROUND: An important protective role of HIV-specific CD4+ Th cells has been evidenced in subjects who control HIV-1 viremia, as well as in highly-exposed HIV-seronegative individuals. The major goals of this work were to detect the presence of HIV-specific CD4+ T cells during primary infection and to identify their |
| 216-T | Complete Supression of Proliferation Despite Persistence of Virus Specific CD4+ T Cells during HIV Viremia Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 216-T Iyasere CA, Tilton JC, Migueles S, Laborico A, Connors M; NIAID, NIH, Bethesda, MD BACKGROUND: Significant frequencies of HIV-specific CD4+ T cells persist in patients with progressive HIV infection despite their inability to mount HIV-specific proliferative responses. To address this dichotomy between frequency and function of HIV-specific CD4+T cells we investigated the mechanisms underlying loss o |
| 217-T | Replicative Senescence of HIV-Specific CD8+ T Cells Defined by CD57. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 217-T Brenchley J, Ambrozak D, Karandikar N, Betts M, Kuruppu J, Douek D, Koup R; NIAID, NIH, Bethesda, MD BACKGROUND: HIV-specific CD8+ T-cell responses play an important role in limiting viral replication and progression to AIDS. Functional defects within this population may be involved in the inability of most individuals to effectively contain viral replication. Here, we examine the ability of HIV-specific CD8+ T cells |
| 218-T | Frequency of HIV-Specific CD8+ T Cells Is not a Predictor of the Breadth of the HIV-Specific CD8+ T-Cell Response. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 218-T Betts M, Ambrozak D, Brenchley J, Douek D, Koup R; NIAID Vaccine Res. Ctr., NIH, Bethesda, MD BACKGROUND: HIV-specific CD8+ T cells are important in controlling viral replication. We recently showed that the HIV-specific CD8+ T-cell frequency is not predictive of viral load in untreated HIV infection, implying that other factors are involved in CD8+ T-cell mediated immune control of HIV. Here, we examined in de |
| 219-T | HIV-1-Specific CD8+ T Lymphocytes in HIV-1 Infected Longterm-Non-progressors (LTNP) and Patients with Absent or Strong Lymphoproliferative (LP) Responses to HIVp24 Have Comparable Phenotypes Suggestive of Memory and not Effector Cytotoxic T-Lymphocytes (CTL). Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 219-T Lange C, Harnisch B, Xu Z, Shankar P, Lee S, Valdez H, Asaad R, Lederman M, Lieberman J; Univ. Hosp., Cleveland, OH BACKGROUND: Many HIV-specific CD8+ cells lack effector cytolytic phenotype and function more like memory cells. If CTL function depends upon antigen-specific CD4+ cell help, we would predict that more antiviral CD8+ cells from LTNP patients or patients with intact LP responses to p24 will be functional effector CTLs. |
| 220-T | HIV-1-Specific CD8+ T Cells Recognize Novel Class I MHC-Restricted Epitopes during Primary HIV-1 Infection. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 220-T Cao J, McNevin J, Fink L, Holte S, Corey L, McElrath MJ; Fred Hutchinson Cancer Res. Ctr., Seattle, WA BACKGROUND: HIV-1-specific CD8+ T cells provide an important defense during acute HIV-1 infection that is mediated through cytolysis of infected cells and release of anti-viral cytokines. To evaluate the earliest T-cell responses induced by infection, we determined the frequency and fine epitope specificity of HIV-1-sp |
| 221-T | Granule Dependent -- but not Granule-Independent -- Mechanisms of Lysis Are Defective in CD8+ T Cells of HIV-Infected, Antiviral Therapy-Treated Individuals Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 221-T Trabattoni D, Piconi S, Migliorino A, Seminari E, Rizzardini G, Biasin M, Maserati R, Clerici M; Univ. Milano BACKGROUND: HIV-specific cytotoxic T-cell (CTL) responses are defective in HIV-infected patients undergoing antiviral therapy (ART); this defect has been attributed to the decreased antigenic burden secondary to ART-associated suppression of HIV-replication. CTL are stimulated by type 1 cytokines and can kill targets v |
| 222-T | Phenotype and Function of Anti-HIV Gag and Pol Specific CD8+ Cytotoxic Lymphocytes in a Cohort of Untreated Chronically HIV-Infected Patients Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 222-T Benito J, Lopez M, Lozano S, Gonzalez-Lahoz J, Soriano V; Inst. de Salud Carlos III, Madrid, Spain BACKGROUND: The use of tetrameric complexes has enabled to easily quantify and analyze different aspects of cytotoxic CD8+ lymphocytes directed against HIV proteins. An impared function of these cells could explain its inefficacy to control HIV replication. To explore this hypothesis we have used the tetramer technolog |
| 223-T | A Systematic Comparison of Methods to Measure HIV-1-Specific CD8 T Cells Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 223-T Samri A, Iglesias E, Kamkamidze G, Sun Y, Carcelain G, Decoville T, Debre P, Autran B; Hosp. Pitie-Salpetriere, Paris, France IFN-γ production measured by flow cytometry or ELISPOT assay give the same frequencies of HIV-specific CD8 T cells; Tetramer staining detects more specific CD8+ T cells than other methods; Pools of optimal peptides or 15-mer overlapping peptides and sums of individual optimal peptides give similar results in ELISPOT assays; CRA and ELISPOT are comparable in their CTL detection capacity when using Rvv; ELISPot assays using peptides are more sensible than those using rVV; Finally, ALT maintain memory CTL responses and clonogenic potential for CTLs compared to progressors. |
| 224-T | IL-15 Inhibits CD95/Fas-Induced Apoptosis of HIV-Specific CD8+ T Cells from HIV-Infected Individuals Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 224-T Mueller Y, Bojczuk P, Witek J, Altman J, Katsikis P; MCP Hahnemann Univ., Philadelphia, PA IL-15 significantly inhibits spontaneous and CD95/Fas-induced apoptosis of effector memory HIV-specific CD8+ T cells. Such inhibition may increase the function and survival of these cells in vivo. IL-15 treatment may prove useful as a therapeutic immunostimulatory strategy for effector memory HIV-specific CD8+ T. |
| 225-T | IL-15 Enhances Effector Function of Memory CD8+ T Cells from HIV-Infected Individuals Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 225-T Mueller Y, Bojczuk P, Witek J, Altman J, Katsikis P; MCP Hahnemann Univ., Philadelphia, PA Our data demonstrate that IL-15 increases the effector function of CD8+ T cells and HIV-specific CD8+ T cells from HIV-infected individuals. Our findings suggest that IL-15 may prove beneficial in clinical studies to enhance the immune response against HIV infection. |
| 226-T | Perforin Expression and IFN-gamma Production are 2 Different Stages of HIV-Specific CD8 T-Cell Differentiation, Independent of Disease Progression Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 226-T Sun Y, Blanc C, Schnuriger A, Faussart A, Samri A, Carcelain G, Yasuko Y, Debre P, Autran B, The ALT Immunoco Study Groups; Hosp. Pitie-Salpetriere, Paris, France BACKGROUND: CD8 T cells control HIV infection in 2 main ways: cytolysis of infected cells, and supression virus proliferation by chemokines and cytokines. METHODS: currently used to evaluate vaccine efficacy are based on IFN-gamma production. We combined the intracellular staining with tetramers and markers of cytotoxi |
| 227-T | The Maturation Phenotype of HIV-Specific CD8+ T Cells Is Associated with Decreased Plasma Viral Load Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 227-T Goepfert P, Edwards B, Bachinsky M, SadasivanNair U, Tussey L; Univ. of Alabama, Birmingham The majority of HIV-specific CD8+ T cells demonstrated a maturation defect when compared to CMV, which was partially overcome in subjects with relative containment of plasma VL. The frequency of CMV-specific CD8+ T cells demonstrated a strong correlation with absolute CD4 T cells suggesting that helper responses optimize virus specific responses even in subjects without evidence of progression to AIDS. |
| 228-T | Comprehensive Characterization of HIV-1-Specific CTL Responses Directed against the Entire Expressed HIV-1 Genome Using a Rapid Peptide-Matrix-System Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 228-T Addo MM, Yu XG, Cohen D, Eldridge RL, Strick D, Johnston MN, Blackard JT, Brander C, Boswell S, Goulder P, Rosenberg E, Altfeld M, Walker BD; Partners AIDS Res. Ctr., Boston, MA BACKGROUND: Cellular immune responses play a critical role in the control of HIV-1. However, no comprehensive analysis of HIV-1 specific T lymphocyte responses directed against the whole expressed genome has been performed thus far. This study evaluates a rapid peptide-matrix based screening approach requiring limited |
| 229-T | Effector CD8 T Cells in HIV-Infected Children Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 229-T Haridas V, McCloskey TW, Pahwa R, Chitnis V, Pahwa S; North Shore-Long Island Jewish Res. Inst., Manhasset, NY BACKGROUND: Effector CD8 T cells utilize perforin to mediate cytotoxicity and perforin expression increases as CD8 T cells undergo maturation from memory to effector cells. CD27 is a marker that has been utilized to distinguish memory (CD27+) from effector (CD27-) subsets of CD8 T cells. Perforin expression is low in C |
| 230-T | IL-15 Augments HIV Specific CD8 T-Cell Responses in Children Chronically Infected with HIV; Implications for Adjuvant Therapy Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 230-T Haridas V, Chitnis V, Kapadia S, Pahwa S North Shore-Long Island Jewish Res. Inst., North Shore Univ. Hosp., New York Univ. Sch. of Med., Manhasset BACKGROUND: MHC class I restricted cytotoxic T cells (CTL) play an important in control of HIV infection. Augmentation of CTL responses is a desirable goal in the management of HIV disease. This study was aimed at evaluating HIV specific CD8 T-cell responses by ELISPOT assay and the effect of exogenous IL-15 on these r |
| 231-T | Viral CTL Escape Mutations do Not Explain HIV Progression in HLA B*5701+ Patients Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 231-T Migueles S, Laborico A, Imamichi H, Connors M; NIAID, NIH, Bethesda, MD BACKGROUND: Evidence is accumulating that HIV-specific CD8+ T-cell responses are critical in restricting virus replication and altering the course of human HIV infection. While high frequencies of B5701-restricted HIV-specific CD8+ T cells are present in some long-term nonprogressors (LTNP), these numbers are similar i |
| 232-T | CTL Response to Lab-Adapted HIV(IIIB) Virus Is not Predictive of Autologous Virus Recognition Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 232-T Lee SK, Xu Z, Lieberman J, Shankar P; Harvard Med. Sch., Boston, MA BACKGROUND: Most laboratory assays measure HIV-specific CD8 T-cell responses to consensus sequences from lab-adapted HIV virus. However the CTL response to laboratory HIV-1 strains may become irrelevant because of the emergence of viral variants in response to selection pressure by CTL. In this study we evaluated the l |
| 233-T | Improvement, but not Normalization, of TCRBV Repertoire after 36 Months of HAART Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 233-T Giovannetti A, Mazzetta F, Marziali M, Pierdominici M, Mezzaroma I, Aiuti F; Univ. La Sapienza, Rome, Italy BACKGROUND: HIV-1 infection induces a progressive decline of CD4+ cells and resulting in disruption of CD4 T-cell antigen receptor variable beta chain (TCRBV) repertoire. In addition, the persistent antigen stimulation promotes expansions of clones bearing selected TCRBV. The HAART-induced suppression of HIV replicatio |
| 234-T | Distribution and Functional Analysis of Memory CD8 and CD4 T Lymphocytes in Different Anatomic Compartments Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 234-T Ellefsen K, Harari A, Champagne P, Sekaly RP, Pantaleo G; CHUV, Lausanne, Switzerland BACKGROUND: 4 subsets of memory CD8 T lymphocytes can be distinguished on the basis of the expression of CD45RA and of CCR7. The analysis of the composition of circulating memory CD8 T cell pool in antiviral immune response has demonstrated a selective impairment of the differentiation of HIV-specific memory CD8+ T cel |
| 235-T | HIV Immunity in Children with Established HIV Infection. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 235-T Weinberg A, Pott G, Patterson J; Univ. of Colorado Hlth. Sci. Ctr., Denver BACKGROUND: Adults with established HIV infection rarely exhibit CD4-mediated HIV-specific immune responses (CMI). Furthermore, HIV-specific cytotoxicity seems to decrease in the absence of viral replication, suggesting that frequent or constant exposure to viral antigens is necessary to maintain HIV-specific immunity. |
| 236-T | Quantitation of CD4 and CD8 T-Cell Proliferation to Soluble Antigens and Inactivated HIV-1 by Flow Cytometry in Various Stages of Disease Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 236-T M. da Silva*1, J. Coderre1, J. Sullivan1, J. Lifson2, and T. Greenough1 The proliferative response to soluble antigens showed mostly a predominance of CD4+ T-cells, but CD8+ T-cells predominate in some cases. AT-2 HIV particles elicited predominantly CD8 T-cell proliferation. Patients with viral load ≥ 10,000/mL have significantly lower proliferative responses to HIV antigens than patients on HAART with viral load < 10,000/mL and LTNP. Similar proliferative responses were found in LTNP and patients on effective HAART. |
| 237-T | CD4 and CD8 Lymphocyte Proliferation Defects Are Tightly Correlated in HIV-Infected Patients and Are Related to Prior Episodes of Circulating CD4 Lymphopenia Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 237-T S. Sieg*, J. Mitchem, D. Bazdar, and M. Lederman CD8 proliferation failure may be the consequence of CD4 helper dysfunction or may reflect a shared acquired insult related to HIV-infection. Prolonged periods of CD4 lymphocytopenia predict subsequent lymphocyte proliferation failure of both CD4+ and CD8+ populations. This system may provide a useful tool to examine CD4/CD8 cell interactions and interdependence in HIV disease. |
| 238-T | Persistence of CD8+ HIV-Specific Response Is Associated with Preservation of the HIV-Specific CD4+ Response Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 238-T G. Alter1, C. M. Tsoukas1, R. LeBlanc1, E. Lefebvre2, H. Dion2, R.-P. Sékaly3, J.-P. Routy1, and N. F. Bernard*1 Starting HAART within the first 4 months of HIV infection preserves both CD4+ and CD8+ HIV specific effector function. The beneficial effect on maintenance of HIV-specific immunity is lost if HAART is started later in the first year of infection. |
| 239-T | T-Cell Immunity Induced by HIV-1 and HIV-2 Infection in Senegal Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 239-T Sow S, Kiviat N, Musey L, Hawes S, Wilson A, Critchlow CW, Diallo-Agne H, Agoff N, McElrath MJ; Univ. of Dakar, Senegal BACKGROUND: HIV-2-infected persons are known to have slower rates of disease progression than those with HIV-1. The lower virulence of HIV-2 may improve the host s ability to mount a more effective immune response. We hypothesized that persons with HIV-2 infection have a higher frequency of HIV-specific T cells, includ |
| 240-T | Cross-Clade Neutralization of HIV-1 Primary Isolates by Human Monoclonal Antibodies that Recognize Conformational V3 Epitopes Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 240-T Gorny MK, Williams C, Volsky B, Revesz K, Cohen S, Polonis V, Honnen WJ, Krachmarov C, Pinter A, Zolla-Pazner S; New York Univ. Sch. of Med., New York BACKGROUND: Several studies suggest that conformation-dependent antibodies (Abs) display more potent neutralizing activity against HIV-1 than do Abs directed against linear epitopes. To test whether anti-V3 monoclonal Abs (mAbs) which preferentially recognize conformation-dependent epitopes have improved neutralizing a |
| 241-T | Cross-Clade Neutralization of Human Immunodeficiency Virus-1 Primary Isolates by Anti-CCR5 Antibodies Present in Long-Term Non-Progressors Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 241-T Barassi C, Pastori C, Ghezzi S, Poli G, Clerici M, Lazzarin A, Lopalco L; San Raffaele Sci. Inst., Italy BACKGROUND: Cells lacking surface CCR5 are resistant to the infection by R5 strains. It has been demonstrated that individuals producing anti-CCR5 antibodies, which cause antigen down-regulation and a CCR5- phenotype, are protected from HIV infection. We searched for anti-CCR5 antibodies in long-term non-progressors (L |
| 242-T | B2.1, A Peptide that Specifically Binds the Broadly HIV-1-Neutralizing, Human Antibody, b12 Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 242-T Menendez A, Zwick M, Montero M, van Houten N, Irving M, Bonnycastle L, Barbas C III, Parren P, Burton DR, Scott J; Simon Fraser Univ., Burnaby, BC, Canada BACKGROUND: Human monoclonal antibody (MAb) b12 recognizes a conformational epitope that overlaps with the CD-4-binding site of the HIV-1 envelope. It neutralizes a broad range of HIV-1 primary isolates and protects against primary virus challenge in animal models. However, b12-like, neutralizing antibodies are rarely |
| 243-T | The Role of Patient Virus Properties and Neutralizing Antibody Responses in Structured Treatment Interruption Therapy Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 243-T A. Trkola*1, H. Kuster1, C. Ruprecht1, C. Leemann1, P. Rusert1, R. Weber1 , B. Hirschel2, and H. Gunthard1 for the Swiss HIV Cohort Study A reduced replication rate of patient isolates and increased sensitivity to antiviral chemokines could be contributing factors in viremia control. Treatment interruption of >4 weeks is required to induce substantial increase in neutralization responses. |
| 244-T | Identification of 2 Distinct Rhesus DC-SIGN Isoforms and Their Potential Roles in Lentiviral Transmission Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 244-T Chen Z, Huang Y, Zhao X, Ba L, Gettie A, Zhang W, Hu B, Ho D; Aaron Diamond AIDS Res. Ctr., Rockefeller Univ., New York, NY BACKGROUND: It has been proposed that dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) on dendritic cells binds and transmits HIV or SIV to target CD4(+) T lymphocytes. METHODS: To study the roles of DC-SIGN in lentiviral transmission using rhesus macaques, we amplified full-leng |
| 245-T | Functional Characterization of Mouse Monoclonal Antibodies Specific for DC-SIGN or DC-SIGNR Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 245-T Baribaud F, Pohlmann S, Leslie G, Ghavimi D, Hoxie J, Mortari F, Doms RW; Univ. of Pennsylvania, Philadelphia BACKGROUND: DC-SIGN, a type II membrane protein with a C-type lectin domain that is highly expressed on mucosal dendritic cells (DCs) and certain macrophages in vivo, binds to ICAM-3, ICAM-2, and human and simian immunodeficiency viruses (HIV and SIV). Virus captured by DC-SIGN can be presented to T cells, resulting in |
| 246-T | Antibody Blocking of DC-SIGN/DC-SIGNR Interaction with HIV and Ebola Glycoproteins Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 246-T Pohlmann S, Baribaud F, Leslie G, Strecker K, Mortari F, Bates P, Doms RW; Univ. of Pennsylvania, Philadelphia BACKGROUND: Dendritic cells (DCs) are among the initial targets of HIV infection and might play a critical role in promoting the establishment of the primary infection. However, these cells are not readily infectable themselves but efficiently transmit virus to susceptible cells. It has been suggested that the C-type l |
| 247-T | DC-SIGN and DC-SIGNR Bind Ebola Glycoproteins and Enhance Infection of Macrophages and Endothelial Cells Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 247-T Pohlmann S, Simmons G, Reeves J, Grogan C, Vandenberghe L, Baribaud F, Netter R, Riley J, Bates P, Doms RW; Univ. of Pennsylvania, Philadelphia BACKGROUND: The C-type (calcium dependent) lectin DC-SIGN and the related molecule DC-SIGNR bind to the HIV envelope glycoprotein (Env) and promote HIV infection of susceptible cells in trans. Both proteins may play roles in vertical and horizontal transmission of HIV. The interaction between DC-SIGN/DC-SIGNR and HIV E |
| 248-T | Peptide Mimics of DC-SIGN-Binding Glycan Structures on HIV gp120. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 248-T Su SV, Lee B; Univ. of California, Los Angeles BACKGROUND: DC-SIGN is a calcium-dependent lectin that binds avidly to HIV Env gp120 and can transfer bound virions to permissive CD4+/co-receptor+ cells. This observation coupled with its expression on submucosal DCs has led to the suggestion that DC-SIGN may play a sentinel role in the sexual transmission of HIV by s |
| 249-T | Increased Binding to DC-SIGN Correlates with Enhanced Transmission of R5-SHIV(SF162P3) but not X4-SHIV(SF33). Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 249-T J. Lue*, M. Hsu, Z. Chen, D. Yang, and C. Cheng-Mayer Better replication of pathogenic variants in DC/T cell co-cultures could account for increased transmission and dissemination of these viruses across mucosal barriers. Whereas more efficient binding to DC-SIGN could underlie the mechanism of enhanced infection of co-cultured T cells by pathogenic R5-SHIVSF162P3, an alternate mechanism is implicated in X4-SHIVSF33A. The presence of additional glycosylation sites in SHIVSF162P3 may be responsible for its enhanced transmission via DC-SIGN binding. |
| 250-T | Clinical Relevance of Tandem-Repeat Polymorphisms in the Genetic Sequence of L-SIGN, a Novel HIV-Transreceptor. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 250-T Lichterfeld M, Nischalke HD, Sohne J, Quirishi N, Sauerbruch T, Spengler U, Rockstroh JK; Univ. of Bonn, Germany BACKGROUND: L-SIGN, a cell-surface C-type lectin primarily expressed on lymph node epithelium has recently been identified as a transreceptor for HIV that binds the HIV with high affinity and can increase virus transmission to HIV target cells. The extracellular domain of this molecule comprises several 23-residue tand |
| 251-T | Role of Macrophage Mannose Receptor in the Binding and Transmission of HIV-1. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 251-T Nguyen DG, Hildreth JE; Johns Hopkins Univ. Sch. of Med., Baltimore, MD BACKGROUND: The human immunodeficiency virus (HIV-1) is an enveloped virus whose surface glycoprotein gp120 binds CD4 and a co-receptor on the target cell membrane to initiate infection. Most of the gp120 glycosylation sites are terminally mannosylated, a pattern common to many pathogens. We have looked at the ability |
| 252-T | Defects in Number and Surface Expression of Co-Stimulatory Molecules on CD11c+ and CD11c- Blood Dendritic Cells in HIV-1-Infected Individuals. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 252-T Barron MA, Blyveis N, Palmer B, MaWhinney S, Wilson CC; Univ. of Colorado Hlth. Sci. Ctr., Denver BACKGROUND: Blood DCs, the precursors to DCs in tissues and lymphoid organs, are characterized by the absence of leukocyte lineage (Lin)-specific antigens and expression of HLA-DR, and have been subcategorized into myeloid DC (mDC) which are Lin(-)DR(+)CD11c(+) and plasmacytoid DC (pDC) which are Lin(-)CD11c(-)IL-3R(Hi |
| 253-T | Dendritic Cell Numbers and Function in an HIV-1-Infected Ugandan Population. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 253-T Jones G, Amjadi P, Watera C, Morlese J, Kaleebu P, Whitworth J, Gotch F, Gilmour J; Imperial Coll. of Sci. Technology and Med., London, UK BACKGROUND: To investigate dendritic cell (DC) numbers and function in HIV-1 seropositive Ugandans infected with non-clade B viruses. METHODS: Blood samples were collected from both HIV-1 seronegative and seropositive Ugandans attending HIV-1 testing facilities in Entebbe. The percentage of blood DC was quantified usin |
| 254-T | Susceptibility of Plasmacytoid Dendritic Cell Precursors (preDC2) to HIV-1 Infection and Their Immunological Responses. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 254-T A. Yonezawa*, T. Hori, A. Takaori, N. Kadowaki, T. Kitawaki, R. Morita, and T. Uchiyama These results indicate that preDC2 respond to HIV-1 with high IFN-α production and consequently inhibit viral replication. Their IFN-α production does not require HIV-1 infection but is likely to be elicited by interaction with some HIV-1 components. We presented evidence that both T-tropic and M-tropic HIV-1 can infect preDC2s. Therefore, it is suggested that a loss of preDC2 by HIV-1 infection may be assosiated with impairment of IFN-α production in HIV-1-infected individuals. |
| 255-T | Impaired Function of Isolated Blood Myeloid and Plasmacytoid Dendritic Cells from HIV-1-Infected Patients. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 255-T Donaghy H, Gazzard B, Gotch F, Patterson S; Imperial Coll. of Sci., Technology, and Med. BACKGROUND: Dendritic cells (DC) are antigen presenting cells that are important in bridging innate and acquired immune responses. In the blood there are at least 2 populations, termed myeloid (myDC) and plasmacytoid (pcDC) DC, which are CD11c+ and CD11c- respectively. myDC are classical antigen presenting cells that m |
| 256-T | Expression of CXCR4 and SDF-1 in Lymphocytes and Dendritic Cells Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 256-T Bermejo M, Martin-Serrano J, de Pablos JL, Alonso JM, Gamallo C, Arenzana-Seisdedos F, Alcami J; Inst. de Salud Carlos III, Majadahonda, Spain BACKGROUND: Our objective was to analyze the expression and regulation of CXCR4 in resting and activated peripheral blood lymphocytes and the expression of SDF-1 in lymph nodes and cultured dendritic cells. METHODS: PBLs were activated with PHA, soluble OKT3 antibody, PMA, SEA, or SDF-1. Membrane and cytosolic CXCR4 ex |
| 257-T | Differential Depletion and Reconstitution on Therapy of the Dendritic Cell Repertoire in Circulating Blood of HIV+ Individuals. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 257-T Chehimi J, Campbell D, Azzoni L, Bacheller D, Jerandi G, Black S, Mounzer K, Shull J, Kostman J, Montaner LJ; Wistar Inst. BACKGROUND: Dendritic cell (DC) subsets are associated with activation and function of innate and adoptive immune responses. Using a panel of new DC markers identifying CD11c(+) myeloid (MDC) and IFN-alpha-secreting plasmacytoid DC (PDC) subsets, we quantified and assessed the functional properties of these 2 major DC |
| 258-T | Relative Resistance to HIV-1 Infection in Vietnamese Exposed Uninfected Intravenous Drug Users Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 258-T Lien TX, Tram LT, Scott-Algara D, David A, Versmisse P, Perez-Bercoff D, Ngai NV, Follezou JY, Theodorou I, Barre-Sinoussi F, Pancino G; Inst. Pasteur, Paris, France BACKGROUND: Most studies on HIV-1-exposed seronegative individuals are focusing on HIV-specific immune responses in sexually exposed populations. This study aimed to analyse immune factors of protection against HIV-1 in intravenous drug-users who are at high risk of infection by systemic route not only for HIV but also |
| 259-T | HIV-1-Specific T-Lymphocyte Responses Are Detectable in a Population of HIV-Negative African Men with Urethritis. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 259-T Galvin S, Garba L, Gama S, Namakwa D, Cohen M, Frelinger J; Univ. of North Carolina, Chapel Hill BACKGROUND: HIV-specific T-lymphocyte responses, especially CD8+ lymphocytes, have been found in small, select groups of highly exposed seronegative persons. To determine whether these responses were detectable in a general African high-risk population with more variable exposure, we performed a study looking for HIV-s |
| 260-T | Strong and Broad HIV-1-Specific T-Cell Immunity in HIV-1-Uninfected Homosexual Men with Very High-Risk Sexual Activities Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 260-T F. Hladik*1, A. Desbien1, J. Lang2, M. J. McElrath1, and 2 These findings suggest that repeated exposure to HIV-1 by very high-risk sexual activity in homosexual men stimulates broad and often pronounced HIV-1-specific T cell immunity. Alternatively, we cannot exclude the possibility that these represent true false-positive responses resulting from recognition of non HIV-1 cross-reactive epitopes. Repeated studies in low-risk HIV-1 seronegative control subjects in addition to the ES will be important to distinguish between these possibilities. |
| 261-T | Protection in Vitro among HIV-Exposed Uninfected Individuals. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 261-T R. John*, S. Arango-Jaramillo, and D. Schwartz EUs can have multiple protective mechanisms with cross clade activity, suggesting vaccines will work against low-dose exposures to multiple clades. |
| 262-T | Immune Correlates of Protection in HIV-Exposed but Uninfected Heterosexual Males Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 262-T Lo Caputo S, Trabattoni D, Vichi F, Fusi ML, Maffeis G, Luzzeri D, Fossati S, Lopalco L, Mazzotta F, Clerici M; Hosp. SM Annunziata, Firenze BACKGROUND: Exposure to HIV in the absence of infection is now well documented. Data are missing on the mucosal immune correlates of this condition in exposed seronegative (ESN) male heterosexual partners of HIV-infected women. METHODS: Analysis of PBMC, seminal fluid and seminal mononuclear cells, and urethral swabs w |
| 263-T | PET-Detected Lymph Node Activation Correlates with Viremia Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 263-T Iyengar S, Chin B, Sabundayo B, Margolick J, Schwartz D; Johns Hopkins Univ., Baltimore, MD BACKGROUND: Macaques infected with SIV showed a progression of lymph node involvement when studied by positron emission tomography (PET). We hypothesized that: PET will reveal anatomically restricted patterns of lymph node activation during early and chronic HIV disease in humans, regardless of route of infection; vire |
| 264-T | Predictors of Disease Progression among LTNP: A 5-Year Follow-Up Study. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 264-T Vicenzi E, Ghezzi S, Vallanti G, Neri F, Douek D, Santagostino E, Gringeri A, Cusini M, Morsica G, Lazzarin A, Veglia F, Poli G; San Raffaele Sci. Inst., Milano, Italy BACKGROUND: The determinants of disease progression in LTNP are unclear at present. METHODS: A cohort of 47 HIV+ LTNP were monitored between 1994 and 1999 in terms of virological, immunologic, and clinical parameters. RESULTS: After 5 years, 24/47 individuals, defined here as late progressors (LP), have experienced eit |
| 265-T | Immunologic Marker Analysis in Real-Time (iMART): Usefulness of Immunophenotypic Markers in Predicting Immunologic and Virologic Outcomes in Ongoing ACTG Trials. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 265-T Mildvan D, Bosch RJ, Kim R, Haas DW, Spritzler J, Kuritzkes D, Nokta M, Landay A, Livnat D, DeGruttola V, Moreno M, Kagan J; Beth Israel Med. Ctr., New York, NY BACKGROUND: Our objective was to identify, from among a variety of phenotypic and functional immune markers under study in ACTG trials, those that are independently predictive of response to potent antiretroviral therapy (ART). METHODS: Naive (CD45RA+/CD62L+) and activated (CD38+/HLA-DR+) subsets of CD4+ and CD8+ T-cel |
| 266-T | Differential Modulation of T Cells and APC by Low-Level Viral Replication under HAART in Chronically HIV-1-Infected Patients. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 266-T Moore EC, Papasavvas E, Sun J, Mounzer K, Shull J, Kostman J, Montaner LJ; Wistar Inst., Philadelphia, PA METHODS: 4 groups of subjects were studied with CD4 counts > 250 for > 6 months with: viral load (VL) 5000 patients on/off HAART (n=17 median HIV RNA=28300); and HIV(-) donors (n=23). T-cells (CD3, CD4, CD28, CD38, CD95, HLADR) and APC (HLADR, CD40, CD80, CD86, CD14, CD16, CD11c, CD54) phenotype and endocytic func |
| 267-T | Plasma Levels of B-Lymphocyte Stimulator (BLyS) TM Protein Increase with HIV Disease Progression Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 267-T B. Rodríguez*1, H. Valdez1, W. Freimuth2, T. Butler2, R. Asaad1, and M. Lederman1 BLyS levels are significantly elevated in patients with HIV infection, when compared with HIV-negative controls. Among patients with HIV infection, BLyS levels correlate inversely with CD4 cell count and directly with plasma HIV RNA. These results suggest that BLyS may play a role in the B-cell activation and hypergammaglobulinemia of HIV infection. |
| 268-T | Prognostic Value of Immunologic and Virologic Markers in Late-Stage HIV-1 Disease: Data from HAVACS. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 268-T J. L. Guest1,2, S. A. Stolfus2, and D. Rimland*1 When CD4+ cell counts are < 51 cells/mm3, CD8+ cell count is the best independent laboratory predictor of survival. Though CD4+ cell counts and HIV-1 RNA levels are superior markers of progression throughout much of the course of HIV-1 and AIDS, at this severely immunocompromised state, CD8+ cell counts are the better marker of survival. Thus, optimal prognostic models require the use of multiple markers to predict progression from this complex disease. Additionally, a rebound of CD4+ cell count above 50 cells/mm3 appears important in prolonging survival, adding evidence to the functional capacity of these CD4+ cells. |
| 269-T | Productive HIV Infection of CD4+ T Cells Lacking Markers of Classic T-Cell Activation: The Role of the Lymphoid Tissue Microenvironment Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 269-T A. Kinter*, A. Moorthy, R. Jackson, and A. S. Fauci These data suggest that HIV can productively infect CD4+ T cells that lack markers of classic T cell activation and this process occurs efficiently in lymphoid tissue. Furthermore, immunosuppressive agents are variably effective in suppressing HIV production depending on the activation state of the HIV-infected CD4+ T cells. |
| 270-T | HIV-1 Infection Alters the Host's Cell Cycle and Transcription Machinery to Allow High HIV-1 Transcription and Efficient Viral Assembly and Dissemination Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 270-T Yang J, Bosche M, Adelsberger JW, Imamichi T, Watkins C, Yeager C, Hosack D, Dennis G, Sherman B, Rupert A, Stevens R, Baseler MW, Lempicki RA; SAIC, Frederick, MD BACKGROUND: The depletion of the CD4+ T lymphocytes during HIV-1 infection is a hallmark of progressive disease. To further understand how the CD4+ T cell transcriptome responds to HIV-1 infection, we examined the expression profiles of ~12,500 genes following in vitro infection of primary CD4+ T cells. METHODS: Primar |
| 271-T | Activated CD4dimCD8bright T Cells Produce IL-4, Are Infected by HIV, and Can Be Detected in Vivo in HIV+ Patients Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 271-T Y. B. Sullivan*, A. Landay, and L. Al-Harthi BACKGROUND: CD4 can be up-regulated on CD8+ T cells generating a CD4(dim)CD8(bright) phenotype. This up-regulation is induced by both anti-CD3/CD28 co-stimulation and superantigen (staphylococcal enterotoxin B, SEB) stimulation. We previously demonstrated that the CD4(dim)CD8(bright) phenotype constitute an activated p |
| 272-T | T-Cell Receptor-Mediated HIV-1 LTR Activation is Strongly Up-Regulated upon CD43 Cross-Linking: Involvement of NFAT and NFkappaB. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 272-T Barat C, Roy J, Tremblay MJ; Laval Univ., Ste-Foy, QC, Canada These results are the first demonstration that CD43 can act as a potent co-stimulating molecule to TCR-mediated HIV-1 LTR activation and this effect is independent of CD28. The suboptimal concentration of anti-CD3 suggested that CD43-mediated signaling could lower the threshold for TCR/CD3 activation. Overall, our results enlarged our understanding of signaling events leading to HIV-1 LTR activation and provided new insight in regard to the 2-signal model in human T cells. |
| 273-T | IL-7 Induces HIV Productive Infection of Naive T Cells: Impact on HIV Pathogenesis in the Naive T-Cell Compartment Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 273-T Managlia EZ, Steffens CM, Landay A, Al-Harthi L; Rush-Presbyterian St. Luke's Med. Ctr., Rush Univ., Chicago, IL BACKGROUND: The predominant cellular targets for HIV productive infection are primed/memory CD4+ T cells. Although HIV gag/pol DNA can be detected in naïve T cells, whether naïve T cells can be productively infected by HIV is still questionable. Given that IL-7 is a prospective therapeutic immunomodulator for the treat |
| 274-T | The Pro-Inflammatory Myeloid-Related Proteins Activate HIV Replication in Infected T Lymphocytes. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 274-T C. Ryckman*, R. Cantin, G. A. Robichaud, M. J. Tremblay, and P. A. Tessier In this study, we demonstrate for the first time that the pro-inflammatory human MRPs stimulate HIV replication in infected T-lymphocytes and that this stimulation is NF-κB-dependent but not dependent of NF-AT. These results highly suggest that MRPs could be significant activators of the amplification of HIV replication during opportunistic infections or other inflammatory conditions leading to AIDS. |
| 275-T | Binding of LFA-1 (CD11a) to ICAM-3 (CD50) and ICAM-2 (CD102) Triggers Transmigration of HIV-1-Infected Monocytes through Mucosal Epithelial Cells. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 275-T Carreno MP, Chomont N, Kazatchkine MD, Irinopoulou T, Krieff C, Si-Mohamed A, Belec L; (INSERM) Hosp. Broussais, Paris, France BACKGROUND: Mono-stratified mucosa, such as the endocervical, urethral, and rectal epithelia could be targeted tissues for transmigration of HIV-1-infected lymphocytes and monocytes contained in cervicovaginal seminal secretions of HIV-infected individuals. Transmigration of HIV-infected mononuclear cells through genit |
| 276-T | Suppression of Interleukin (IL)-12 p40 Transcription by Acute HIV Infection: Disruption of Nuclear Factor Binding and Inhibition of MAP Kinase Activation Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 276-T Chambers KA, Angel JB; Ottawa Health Res. Inst., Univ. of Ottawa, ON, Canada BACKGROUND: Progressive immunodeficiency in HIV infection is paralleled by a decrease in IL-12 production, a cytokine crucial for the generation of cellular immune function. Here we examine the molecular mechanism by which acute HIV infection suppresses transcription of the IL-12 p40 gene in myeloid cells. METHODS: Nu |
| 277-T | Differential Effects of IL-7 and IL-15 on Cytolytic Activity in Natural Killer Cells from HIV+ Patients. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 277-T Lum J, Mbisa G, Lynch DH, Nie Z, Hawley-Foss N, Badley AD; Ottawa Hlth. Res. Inst., ON, Canada BACKGROUND: Attempts to eradicate HIV reservoirs have so far been unsuccessful and highlight the need for novel therapeutic approaches. In vitro treatment of PBL from HIV+ donors with TRAIL/Apo2L induces cell death and significantly reduces the levels of HIV in resting memory cells and macrophages. It is therefore of i |
| 278-T | Cytoplasmic p21 WAF1/Cip1 Protects CD4 T Cells from HIV Mediated Apoptosis Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 278-T Gomez T, Ricardo R, Holz-Heppelmann C, Villasis-Keever A, Vlahakis S, Paya CV; Mayo Clin., Rochester, MN BACKGROUND: p21 WAF1/Cip1, a universal inhibitor of cyclin-dependent kinase activity, mediates cell cycle arrest and apoptosis when localized in the nucleus. In addition, p21 WAF1/Cip1 has also been shown to play an anti-apoptotic role in monocytes and transformed cells when localized in the cytoplasm. In this study we |
| 279-T | Interleukin-7 Receptor (CD127) Expression and RNA Accumulation in CD8+ T Cells Is Down-Regulated by TNFalpha Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 279-T Komsic A, Angel JB; Ottawa Hlth. Res. Inst., Univ. of Ottawa, ON, Canada BACKGROUND: Lack of immunologic control of viral replication is likely due to inadequate cytotoxic T lymphocyte (CTL) activity. IL-7 and its signaling via the IL-7 receptor (IL-7R/CD127) are required for normal CTL activity and since the down-regulation of this receptor is observed on CD8 T-cells of HIV+ individuals, i |
| 280-T | Comparison of Multiple Analytical Methods to Measure Cytokine Production from Single T Cells. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 280-T R. P. Bucy*1, G. Marshall1, P. Goepfert1, J. Jacobson2, and J. M. Kilby1 The frequency of cytokine-producing T cells is dependent on cell density during stimulation and correlates well with the frequency of cytokine mRNA+ cells. Analysis of cytokine expression by the IHC method has superior sensitivity compared to flow and can be performed at high cell density, independent of the inherent frequency of precursor cells. |
| 281-T | In Vitro Derived Dendritic Cells Express Native HIV-1 Clade C gag Gene after Infection with a Recombinant Adenoviral Vector Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 281-T Perumal D, Papagatsias T, Roberts M, Athanasopoulos T, Gray C, Dickson G, Gotch F, Patterson S; Imperial Coll. Sch. of Sci., Technology and Med., London, UK BACKGROUND: The unique ability of dendritic cells (DC) to induce primary cellular immune responses makes them optimal candidates for vaccination protocols. In this study we are using in vitro derived dermal dendritic cells (DDC) and Langerhans-type cells (LC) as a tool to analyse T-cell response to new adenoviral vacci |
| 282-T | Protease Inhibitors Reduce Apoptosis through a Mechanism which Is Independent of Caspase Inhibition. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 282-T Phenix BN, Lum J, Nie Z, Sanchez-Dardon J, Badley AD; Ottawa Hlth. Res. Inst., ON, Canada BACKGROUND: Protease inhibitor (PI)-induced improvements in CD4 T-cell counts may be in part independent of PI effects on HIV replication. We and others have previously demonstrated that PIs inhibit apoptosis in both infected and uninfected T cells. To ascertain the mechanism by which PIs exert their anti-apoptotic eff |
| 283-T | Vitamin A, Pneumonia, HIV Infection, and Type-1 Cytokine Immunity Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 283-T J. Jason*1, L. K. Archibald1, O. C. Nwanyanwu1, A. L. Sowell1, I. Buchanan1, J. Larned1, M. Bell1, P. N. Kazembe2, H. Dobbie2, and W. R. Jarvis1 In these children, lower vitamin A levels were associated with type-1/pro-inflammatory cytokine profiles, fewer cells making IL-10, a macrophage-inhibitory cytokine, and proportionately more NK cells. These would all assist in anti-HIV and anti-mycobacterial immunity. In settings where infections with type-1 organisms predominate, moderately low vitamin A levels might actually be preferable to the currently defined "normal" levels. |
| 284-T | Human Infection with Simian Foamy Viruses: Preliminary Results from an Immunologic Study. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 284-T Spira TJ, Lam L, Boneva RS, Switzer WM, Cummins JM, Heneine W, Folks TM, Chapman LE; CDC, Atlanta, GA BACKGROUND: Simian foamy virus (SFV) infection has been confirmed in 11 men occupationally exposed to nonhuman primates. The purpose of this cohort study is to determine if there are any immunologic consequences of such infection in man. METHODS: SFV-infected men were enrolled in this study. Peripheral blood specimens |
| 285-W | Modification of HIV-1 nef and tat for DNA Vaccine Design. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 285-W Gurner D, Huang Y, Chen Z, Song Y, Zhang W, Zhao X, Ho DD; Aaron Diamond AIDS Res. Ctr., Rockefeller Univ., New York, NY BACKGROUND: There is increasing evidence in support of the immunogenic importance of HIV-1 regulatory genes. We have therefore been interested in incorporating nef and tat into our DNA vaccine design, but first had to address certain undesirable properties of these viral proteins. METHODS: Using overlapping PCR, we syn |
| 286-W | A Novel Topical DNA Vaccine (DermaVir) for the Induction of T-Cell Immunity Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 286-W Lisziewicz J, Xu J, Trocio J, Whitman L, Markham P, Arya S, Behr JP, Lori F; Res. Inst. for Genetic and Human Therapy (RIGHT), Washington, DC BACKGROUND: We have recently described induction of potent Th-1 polarized HIV-specific T cell immunity by ex vivo cultured autologous genetically-modified dendritic cells (DC) in macaques. Here we describe a similarly effective vaccination based on in vivo genetic manipulation of DC. METHODS: We developed a practical, |
| 287-W | Transmucosal Delivery of CpG ODN Applied to the Genital Mucosa Protects Mice against Intravaginal HSV-2 Infection Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 287-W Sajic D, Ashkar AA, Patrick AJ, McCluskie MJ, Davis HL, Levine KL, Holl R, Rosenthal KL; McMaster Univ. Hlth. Sci. Ctr., Hamilton, ON, Canada BACKGROUND: Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG dinucleotides have been shown to induce potent innate immune responses against infectious agents and trigger Th1-like immune activation. Here, we investigated whether transmucosal delivery of CpG ODN applied to the genital mucosa could protec |
| 288-W | Generating Novel HIV-1 Envelope Vaccine Candidates Using DNA Shuffling Technology Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 288-W Xu L, Du X, Zhang W, Burton DR, Parren PW, Whalen RG; Maxygen, Inc., Redwood City, CA BACKGROUND: DNA shuffling captures the power of genetic recombination in a simple test-tube format. Typically, homologous genes are used to create large libraries of highly chimeric sequences encoding proteins that exhibit novel and improved biological properties. This technology has been used to improve enzymes, antib |
| 289-W | Vaccination of Rhesus Macaques with HIV-1 Tat Protein Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 289-W Silvera P, Greenhouse J, Yalley-Ogunro J, Richardson MW, Mirchandani J, Khalili K, Zagury JF, Lewis M, Rappaport J; Southern Res. Inst., Frederick, MD BACKGROUND: The regulatory proteins Nef, Rev, and Tat of HIV-1 which are expressed early in the virus life cycle are attractive targets for vaccine development, since the induction of effective immune responses targeting these proteins may best control virus replication. Here, we investigated whether vaccination with H |
| 290-W | Characterization of Humoral Immune Response against the Wild Type and Variable Loop-Deleted HIV-1 Envelope Glycoproteins. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 290-W Kim YB, Han DP, Cao C, Cho MW; NIH, Bethesda, MD BACKGROUND: It is extremely difficult to elicit broadly cross-reactive neutralizing antibodies (Nabs) against HIV-1. In this study, we compared antibody responses against the wild type and variable-loop deleted HIV-1 envelopes. The specific goals were: to identify immunogenic epitopes on gp120; to determine whether it |
| 291-W | Enhanced Immunogenicity of Nasally Administered HIV Peptides Using Mucoadhesive Polymers. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 291-W Nordone SK, Staats HF; Duke Univ. Med. Ctr., Durham, NC BACKGROUND: Protective immunity against sexually transmitted HIV through immunization will likely depend upon antigen-specific antibody and cytotoxic lymphocytes (CTL) at local mucosal surfaces. Induction of potent, local antigen-specific immunity requires mucosal delivery of the immunogen. We have previously shown tha |
| 292-W | Intranasal Immunization with Inactivated gp120-Depleted HIV-1 Immunogen (Remune) plus CpG ODN Induces Potent Immune Responses in the Genital Tract and Protection against Intravaginal Challenge. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 292-W Dumais N, Jiang J, Moss RB, Davis HL, Rosenthal KL; McMaster Univ. Hlth. Sci. Ctr., Hamilton, ON, Canada BACKGROUND: Development of vaccines capable of preventing the transmission or limiting the severity of sexually transmitted viruses, such as HIV, will likely be dependent on the induction of a potent long-lasting mucosal immune response in the genital tract. In this study, we evaluated the immune responses and protecti |
| 293-W | Novel Method of HIV-1 Inactivation and Its Application towards Development of a Whole-Killed HIV Vaccine Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 293-W P. Ilyinskii, L. Lallos, and T. Castor CFI technique is effective in HIV inactivation. The mechanism of inactivation includes partial destruction of virion without compromising the integrity and antigenicity of viral proteins. If the inactivated viral preparation produced by this method elicits a beneficial immune response, genetically attenuated HIV strains of different clades may be used to provide for greater safety and broader protection. This vaccine technology is inexpensive, amenable to large-scale processing, and can be readily implemented in a host country site. |
| 294-W | HIV Seropositivity among Uninfected HIV Vaccine Recipients. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 294-W Ackers ML, Parekh B, Evans TG, Berman P, Phillips S, Allen M, McDougal JS; CDC, Atlanta, GA BACKGROUND: Since 1987, > 6000 individuals worldwide have received HIV preventive vaccine constructs. Many of these constructs elicit antibodies that may be detected by standard serologic tests (enzyme immunoassays [EIA], rapid tests, and Western blot [WB]) and result in vaccine recipients sera being identified as reac |
| 295-W | Contamination of Fetal Bovine Serum with Bovine Viral Diarrhea Virus: An Issue for Manufacturers of HIV-1 Vaccines Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 295-W L. Jagodzinski*1, J. Cooley1, S. Kelly1, T. VanCott1, and N. Michael2 95% of the FBS lots screened were contaminated with detectable amounts of BVDV viral RNA. Since BVDV can infect chicken embryo cells and thus be co-propagated with HIV-1 MVA, HIV-1 MVA vaccine preparations could be contaminated with BVDV. The injection of BVDV-contaminated HIV-1 MVA vaccine into immune compromised or healthy individuals could lead to immunological complications that could compromise HIV-1 vaccine trials. |
| 296-W | Abstract not available. |
| 297-W | Vaccine Strategies for the Induction of Neutralizing Antibodies and Cellular Immune Responses against HIV-1 Subtype C Strains. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 297-W Barnett SW, Srivastava IR, zur Megede J, Lian Y, Sun Y, Hilt S, Kan E, Scriba T, Engelbrecht S, Janse van E, Otten G, Ulmer JB, Donnelly JJ; Chiron Corp., Emeryville, CA BACKGROUND: Protection against HIV infection will require potent and broad neutralizing antibodies and cellular immune responses in vaccinated individuals exposed to virus challenge. Subtype C strains are being transmitted at alarmingly high rates in sub-Saharan Africa and India . We have thus |
| 298-W | Recombinant SV40 as a Vaccine Delivery Vehicle against HIV-1 Envelope gp120. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 298-W McKee H, Strayer D; Jefferson Med. Coll., Philadelphia, PA BACKGROUND: Among the most promising approaches to developing a vaccine against HIV-1 is the use of live viral vectors to deliver antigen-coding sequences in vivo. Since recombinant SV40 vectors (rSV40) do not elicit neutralizing responses against themselves, we hypothesized that they might be useful in boosting immune |
| 299-W | Rhabdovirus-Based Vectors Expressing HIV-1 Env or Gag Induce Vigorous Cellular Responses against HIV-1 and Infect Efficiently Human Dendritic Cells. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 299-W McGettigan J, Foley HD, Sarma S, Otero M, Siler CA, Orenstein J, Pomerantz RJ, Schnell MJ; Thomas Jefferson Univ., Philadelphia, PA BACKGROUND: Our previous experiments with replication-competent vaccine strain-based rabies virus (RV) expressing HIV-1 envelope protein from both a laboratory-adapted HIV-1 strain (NL4-3) and a primary HIV-1 isolate (89.6) showed that RV-based vectors are excellent for B-cell priming. Here we analyze the cellular resp |
| 300-W | A Novel Chimeric Rev, Tat, and Nef Antigen as a Component of an SIV/HIV Vaccine Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 300-W Hel Z, Johnson JM, Tryniszewska E, Tsai WP, Harrod R, Fullen J, Tartaglia J, Franchini G; NCI, NIH, Bethesda, MD BACKGROUND: HIV-1 regulatory proteins Rev, Tat, and Nef are expressed early after infection and represent attractive targets to be included in a vaccine for AIDS. However, the low level expression of these proteins in mammalian cells and the potential immunosuppressive activity of Tat and Nef, as such, represent a limi |
| 301-W | Evolution in Culture of Constitutively Dead, Conditionally Live HIV-1 Genomes, an Attenuated Viral Vaccine with the Regulated Replication. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 301-W Khoroshev M, Jeang KT, Smith S; New Jersey Med. Sch., Newark BACKGROUND: Constitutively dead, conditionally live (CDCL) HIV-1 genomes are intended to improve the safety profile of an attenuated HIV-1 vaccine. The Tat/TAR axis was disrupted and the virus is constitutively dead. Replication of the virus is conditionally dependent on doxycycline. METHODS: In the NL4-3 backbone, the |
| 302-W | Comparative Analysis of Immune Response Elicited in Rabbits by the Combined Use of Recombinant Avipoxviruses, Plasmids, and Virus-Like Particles (VLPs) in Prime-Boost Vaccination Protocols Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 302-W Radaelli A, De Giuli C, Elli V, Vicenti E, Poli G, Basavecchia V, Zanotto C; Univ. of Milan BACKGROUND: The induction of both a strong neutralizing humoral and a cytotoxic T-lymphocyte response is widely seen as critical to the development of a protective immunity to infection by the human immunodeficiency virus (HIV). 3 different prime-boost immunization protocols were tested in rabbits and their immune resp |
| 303-W | Potentiation of SIV-Specific CD4+ and CD8+ T-Cell Responses by a DNA-SIV and NYVAC-SIV Prime-Boost Regimen Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 303-W Z. Hel1, W-P. Tsai*1, A. Thornton1, J. Nacsa1, L. Giuliani1, E. Tryniszewska1, 2, M. Poudyal1, D. Venzon1 , X. Wang3, J. Altman3 , D. I. Watkins4, W. Lu5 , A. von Gegerfelt5, B. K. Felber5, J. Tartaglia6, G. N. Pavlakis5, and G. Franchini1 The combination of these vaccine modalities may represent a valuable strategy in the development of a vaccine for HIV. |
| 304-W | Differential Epitope-Recognition by Antibodies Elicited during Immunization with the DELTA V2 and SF162 Envelopes and During Infection with SHIVSF162P4 Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 304-W Buckner C, Gettie A, Blanchard J, Barnett S, Srivastava I, VanDorsten K, Stamatatos L; Aaron Diamond AIDS Res. Ctr., Rockefeller Univ., New York, NY BACKGROUND: Immunization of rhesus macaques with a mutated form of the SF162 envelope lacking the V2 loop (DELTAV2), elicits antibodies that neutralize several heterologous primary HIV-1 isolates. In contrast, immunization with the unmodified SF162 envelope elicits neutralizing antibodies primarily against the homologo |
| 305-W | Modifications in the Cytoplasmic Domain of HIV-1 Env Allow Exposure of the Conserved Co-Receptor-Binding Site and Enhance Neutralization Sensitivity Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 305-W Baribaud F, Edwards T, Wyss S, Reeves J, Zolla-Pazner S, Hoxie J, Doms RW; Univ. of Pennsylvania, Philadelphia BACKGROUND: We recently described a CD4-independent variant of HXBc2 termed IIIBx. IIIBx was generated by serial in vivo passage of HXBc2 on CD4-negative, CXCR4-positive BC7 cells. A molecular clone from this swarm, designated 8x, was PCR-amplified and was shown to bind directly to CXCR4 and to mediate CD4-independent |
| 306-W | Enhanced Neutralizing Antibody Responses Induced in Rhesus Macaques by o-gp140DV2 SF162 in a Prime-Boost Regimen Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 306-W Srivastava I, Kan E, Sun Y, Stamatatos L, Montefiori D, Otten G, O'Hagan D, Singh M, Donnelly JJ, Ulmer J, Barnett S; Chiron Corp., Emeryville, CA BACKGROUND: A major emphasis of our work in HIV vaccine development has been towards designing strategies for the induction of potent cellular and humoral responses. For the induction of humoral responses, our focus has been on the induction of high avidity and primary isolate neutralizing antibodies. We have demonstra |
| 307-W | Effect of DC Pulsed with Oligo-Arginine Conjugated HIV Polypeptides in HLA-A2 Transgenic Mice Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 307-W Kundu-Raychaudhuri SK, Rothbard J, Engleman EG, Merigan TC; Stanford Univ. Med. Ctr., Palo Alto BACKGROUND: The best strategy for controlling the HIV epidemic remains the development of an efficacious vaccine. The successful preclinical evaluation of any vaccination approach requires that laboratory animals respond to epitopes that are immunogenic in humans. HLA-A2.1K(b) transgenic mice represent a suitable model |
| 308-W | Novel HIV Immunogen: HIV Gag-Env Chimerical Protein Conjugated with Potent Immunomodulator Polyoxidonium. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 308-W Nikolaeva I, Chevalier A, Korobova S, Ignatjeva G, Karamov E, Nekrasov A, Khaitov R, Sidorovich I; Inst. of Immunology RF Ministry of Hlth., Moscow BACKGROUND: Candidate HIV vaccines inducing neutralizing antibody against HIV primary isolates and cytotoxic T-cell responses are being sought. HIV envelope is the primary target for neutralizing antibodies in HIV-infected persons, while most CTL epitopes are located within relatively conserved domains of gag-coded pro |
| 309-W | Class I-Restricted Cross-Presentation of HIV-1 Vaccinal Lipopeptides in Human Dendritic Cells Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 309-W M. Andrieu*1, J-F. Desoutter1, E. Loing2, D. Hanau3, J-G Guillet1, and A. Hosmalin1 BACKGROUND: Lipopeptides currently used in HIV vaccine trials induce strong multi-epitopic CD8+ T-cell specific responses. We have addressed the antigen presentation pathway of these lipopeptides in dendritic cells (DC), which are the only antigen-presenting cells able to stimulate naïve T cells, hence to initiate vacc |
| 310-W | Generation of Th1-Type HIV-1-Specific Immune Responses to gp120-Depleted HIV-1 Immunogen in Mice with Preexistent Th2 Immune Profile: Relevance to Vaccination in Developing Countries Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 310-W M. Ayash-Rashkovsky1, Z. Weisman1, J. Diveley2, R. B. Moss2, G. Borkow1, and Z. Bentwich*1 These results lend strong support to the possibility of using CpG ODN as a Th1-inducing adjuvant in combination with candidate HIV vaccines, when immunizing populations with a strong preexistent Th2 immune profile, without altering their immune background and protective anti-parasitic immune responses. |
| 311-W | A Glycoprotein-Deficient Rhabdovirus Expressing HIV-1 gp160 Mimics an HIV-1-Like Tropism and Targets Human Dendritic Cells: Indication for a Novel HIV-1 Vaccine Approach. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 311-W Foley HD, McGettigan J, Otero M, Siler CA, Orenstein J, Pomerantz RJ, Schnell MJ; Thomas Jefferson Univ., Philadelphia, PA and George Washington Univ. Med. Ctr., Washington, DC BACKGROUND: No live-viral vector with an HIV-1-like tropism which does not integrate into the host cell genome is under investigation as an HIV-1 vaccine. We showed previously that rabies virus (RV) vaccine strain-based vectors induce vigorous immune responses against the expressed HIV-1 proteins. On the basis of the r |
| 312-W | Control of Viral Load Rebound during Treatment Interruptions in Macaques with AIDS Induced by a Novel Topical DNA Immunization (DermaVir) Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 312-W Lisziewicz J, Xu J, Trocio J, Whitman L, Lewis MG, Lori F; Res. Inst. for Genetic and Human Therapy, Washington, DC BACKGROUND: T-cell-mediated immunity can be induced during acute infection by structured treatment interruptions (STI-HAART). However, the hope of inducing protective immunity through auto-vaccination is tempered by the fact that early diagnosis of the infection is a rather rare occurrence, and immune control is not ac |
| 313-W | Containment of Viral Rebound after Antiretroviral Therapy Suspension in Macaques Chronically Infected with SIV following Vaccination with NYVAC-SIV Recombinant Vaccines Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 313-W Tryniszewska E, Lewis MG, Hel Z, Nacsa J, Tsai WP, Stevceva L, Parks RW, Moniuszko M, Cairns S, Smith KA, Tartaglia J, Franchini G; NCI, NIH, Bethesda, MD BACKGROUND: Highly active antiretroviral therapy (HAART) of HIV-1-infected individuals has dramatically decreased the mortality and morbidity of chronic HIV-1 infection. Toxicity, accessibility, and affordability of prolonged HAART treatment limits its use in both developed and developing countries. In addition, while |
| 314-W | Therapeutic Immunization with Remune Alters Kinetics of Viral Rebound after Analytical Therapy Interruption (ATI). Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 314-W Bucy RP, Moss RB, Gersten M, The 06A Study Team; Univ. of Alabama, Birmingham BACKGROUND: The benefit of therapeutic immunization may be most clearly determined by analyzing the kinetics of viral rebound when patients stop all antiretroviral medications. METHODS: Subjects from a randomized adjuvant-controlled Remune vaccine trial designed to detect clinical endpoints, who had maintained plasma H |
| 315-W | Immunogenicity of Remune in Subjects with Established HIV Infection. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 315-W Robbins G, Addo MM, Troung H, Rathod A, Habeeb K, Basgoz N, Davis B, Heller H, Walker B, Rosenberg E; Massachusetts Gen. Hosp., Boston BACKGROUND: Virus-specific CD4 T helper (Th) cells are believed to play a pivotal role in immune control of HIV infection, however this immune response is weak or absent in the majority of chronically infected persons. One potential therapeutic vaccine designed to restore HIV-specific Th cell function is Remune, an env |
| 316-W | Induction of HIV-1-Specific Reactivity in CD8+ and CD4+ T Cells from Patients on Combination Antiretroviral Drug Therapy by Dendritic Cells Loaded with HIV-1-Infected Apoptotic Cells. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 316-W Zhao XQ, Huang XL, Borowski L, Gupta P, Fan Z, Watkins S, Thomas E, Rinaldo C Jr; Univ. of Pittsburgh, PA BACKGROUND: Efficient control of HIV-1 infection during combination antiviral drug therapy may require recovery of anti-HIV-1 T-cell responses to residual, autologous virus. We have developed a model for induction of anti-HIV-1 responses in CD8+ and CD4+ T cells of treated subjects by dendritic cells (DC) loaded with v |
| 317-W | Generation of Monocyte-Derived Dendritic Cells (MD-DC) in Clinical GMP Conditions and their Ability to Activate CD4 and CD8 T Cells to HIV Antigens in Early HIV+ Individuals Receiving HAART Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 317-W Lejeune M, Garcia F, Gil C, Alcami J, Joseph J, Miro J, Plana M, Gatell JM, Gallart T; Univ. of Barcelona, Madrid, Spain BACKGROUND: Myeloid DC activate both naïve and memory CD4+ and CD8+ T to non-infectious antigens of the exogenous pathway, and constitute the most potent cellular adjuvant for an active immunotherapy against HIV infection. MD-DC are more accessible in a clinical setting. Objectives were to optimize the generation of MD |
| 318-W | Augmentation of HIV-1-Specific Memory Subsets of T Lymphocytes and Decrease of Immune Activation in HIV-1+ Individuals Treated with a Therapeutic Vaccine plus Antiretrovirals: Impact on Viral Load Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 318-W Fernandez-Cruz E, Navarro J, Abad ML, Diaz-Munoz L, Canto C, Carbone J, Moreno S, Clotet B, Perez Molina J, Gatell JM, Munoz-Fernandez M, The Spanish 2102 Team; Univ. Hosp. Gregorio Maranon, Madrid, Spain BACKGROUND: We examined the immunomodulatory efficacy of a HIV-1 therapeutic vaccine (an inactivated gp120-depleted HIV-1 immunogen in IFA, REMUNETM) in 243 HIV+ chronically infected subjects while receiving either ART or HAART in a 3-year, double-blind, placebo (IFA)-controlled trial. METHODS: We have studied function |
| 319-W | Association of HLA-B22 with Increased Plasma HIV-1 RNA Concentration and Accelerated Progression to AIDS in Caucasian Cohorts. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 319-W Dorak MT, Tang J, Tang S, Coutinho R, Goedert JJ, Detels R, Kaslow RA; Univ. of Alabama, Birmingham BACKGROUND: An association of alleles in the HLA-B22 group (B*54, *55 and *56) with faster HIV disease progression has been suggested. B22 group alleles belong to the B7 supertype, as do B*35 and the closely related B*53, also associated with faster progression. B7 supertype alleles preferentially bind CTL peptides con |
| 320-W | Homozygosity for HLA-Bw4 Is Not Associated with Protection of HIV-1-Infected Persons of African Ancestry. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 320-W Kaslow RA, Tang J, Dorak MT, Tang S, Musonda R, Karita E, Wilson C, Allen S; Univ. of Alabama, Birmingham BACKGROUND: In HIV-1+ Caucasians, homozygosity at the serogroup level for the Bw4 epitope has been associated with better control of HIV/AID appeared independent of a number of reported markers of progression. Interaction between Bw4 and its natural killer (NK) cell receptor was suggested as a possible mechanism. We se |
| 321-W | The Association of Polymorphisms in HLA Class I and TAP Genes with Resistance to HIV-1 Infection Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 321-W Liu C, Carrington M, Kaslow RA, Rinaldo C, Jacobson L, Margolick J, Phair J, Detels R; Univ. of California, Los Angeles BACKGROUND: Several studies have shown that human leukocyte antigen (HLA)-restricted immune responses are involved in resistance to viral infection. The main objective of this study was to examine relationships of HLA class I and the transporter associated with antigen processing (TAP) genes with resistance to human im |
| 322-W | Polymorphisms of Host Genes in Exposed Seronegative Individuals: Impact on HIV-1 Transmission. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 322-W Hwangbo Y, McElrath J, Liu H, Lee J, Zhu H, Corey L, Zhu T; Univ. of Washington Sch. of Med., Seattle BACKGROUND: Polymorphisms in host genes have been shown to affect HIV-1 transmission and disease progression. Our objective was to determine the overall effect of host genes on HIV-1 transmission by characterizing the genetic polymorphisms in CCR1, CCR2, CCR5, and RANTES in exposed seronegative (ES) individuals. METHOD |
| 323-W | HIV-Specific CD8+ T-Cell Responses from HLA-B*57-Positive Adolescents Preferentially Target the Gag Protein Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 323-W Bansal A, Sabbaj S, Edwards B, Perkins C, Ritter GD, Tang J, Kaslow RA, Wilson C, Mulligan M, Goepfert P, The REACH Cohort; Univ. of Alabama, Birmingham BACKGROUND: HIV-infected subjects expressing the class I allele, HLA-B*57, are among those who progress to AIDS more slowly when compared to other individuals. However, no data exist in infected subjects to suggest that favorable alleles are associated with different HIV-specific CD8+ T-cell responses when compared to |
| 324-W | Protective Effect of IL4 -589T Polymorphism on HIV-1 Disease Progression: Relationship with Viral Load Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 324-W Nakayama EE, Meyer L, Iwamoto A, Persoz A, Nagai Y, Rouzioux C, Delfraissy JF, Debre P, McIlroy D, Theodorou I, Shioda T, The SEROCO Study Group; Res. Inst. for Microbial Diseases, Osaka Univ., Japan BACKGROUND: IL4 down-regulates CCR5 expression and thus inhibits replication of HIV-1 R5 virus in human T cells and macrophages. On the other hand, IL4 up-regulates the expression of CXCR4 and enhances the replication of X4 variants. IL4 -589T allele is a single nucleotide polymorphism with a C to T exchange at positio |
| 325-W.html | Host Genetic Profiles Strongly Correlate with Virologic and Immunologic Outcomes in HIV-1 Seroprevalent and Primarily African American Adolescents. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 325-W Tang J, Wilson CM, Meleth S, Shaen M, Myracle A, Lobashevsky E, Mulligan M, Kaslow RA, The REACH Cohort Study Group; Univ. of Alabama, Birmingham BACKGROUND: HIV-1 pathogenesis can be regulated by host genetic variations at several loci involved in natural and acquired immunity. We evaluated the correlation between host genetic profiles (defined by HLA and HIV-1 coreceptor variants) and the virologic and immunologic outcomes among HIV-1-infected adolescents from |
| 326-W | A Novel Genetic Variant of CD28 Gene Is Associated with Susceptibility to HIV Infection. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 326-W Soriano A, Martinez C, Garcia F, Plana M, Palou E, Arostegui J, Leujeune M, Joseph J, Miro J, del Romero J, Rodriguez C, Barrasa A, Lorenzo JI, Lozano F, Gatell JM, Gallart T; Hosp. Clinic-IDIBAPS, Univ. of Barcelona BACKGROUND: CD28 plays an essential role in the effectiveness of T-cell immune responses. In addition, CD28 co-stimulation of CD4+ T-cells confers resistance to in vitro infection by R5-tropic HIV-1 strains by down-regulating CCR5, while it increases CXCR4 expression. We analyzed the presence of polymorphisms in the 5 |
| 327-W | Human Major Histocompatibility Complex (HLA) Class I Variants in HIV-1-Infected Zambians and Their Relative Effect on Plasma Viral RNA Concentration in the Absence of Antiretroviral Therapy Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 327-W Tang J, Tang S, Fideli U, Musonda R, Lobashevsky E, Allen S, Aldrovandi G, Kaslow RA; Univ. of Alabama, Birmingham BACKGROUND: Allelic forms of human major histocompatibility complex (HLA) class I molecules differentially present endogenous antigens to CD8+ cytotoxic T-lymphocytes (CTLs) for immune surveillance. The impact of HLA alleles on HIV-1 disease progression has often differed in the magnitude and consistency across cohorts |
| 328-W | Liver Is a Major Organ for Clearing SIV Particles in Rhesus Monkeys. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 328-W Zhang L, Dailey PJ, Gettie A, Ho D; Aaron Diamond AIDS Res. Ctr., Rockefeller Univ., New York, NY BACKGROUND: Infection by HIV or SIV is characterized by the rapid turnover of both viral particles and productively infected cells. Using the SIV/rhesus macaque model, it has been reported that the clearance of exogenously infused SIV particles is exceedingly fast in vivo, with half-lives on the order of minutes. The a |
| 329-W | Vaginal CD4+ T Cells are Rapidly Depleted in SIV Infection Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 329-W R. Veazey*1, P. Marx1,2, and A. Lackner1 This study demonstrates that by 14 days of SIV infection, CD4+ T cells are markedly depleted in the vaginal mucosa. This suggests that in early SIV infection, vaginal mucosal immune responses may be markedly impaired. Moreover, this demonstrates that there are large numbers of activated, CD4+ T cells co-expressing CCR5 residing within the vaginal mucosa of normal, uninfected macaques and that these cells are specifically targeted for infection, viral amplification, and elimination by lytic viral replication in early SIV infection. |
| 330-W | Decreased Frequency of CMV-Specific CD4+ T Lymphocytes in SIV-Infected Rhesus Macaques: Inverse Relationship with CMV Viremia Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 330-W A. Kaur*, C. L. Hale, N. Kassis, B. Noren, M. Simon, and R. P. Johnson Loss of CMV-specific CD4+ T lymphocytes during the course of pathogenic lentivirus infection appears to play an important role in CMV reactivation. Study of factors predisposing to loss of antigen-specific CD4+ T cells is likely to facilitate insight in to the pathogenesis of CMV infection in AIDS. |
| 331-W | Cell Injury and Apoptosis Genes Increased in Frontal Gray Matter of SIVmac251-Infected Rhesus Macaque Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 331-W Westmoreland S, Boisvert K, Zarycki J, Jung J, Lackner A; Harvard Med. Sch. BACKGROUND: HIV-1 results in AIDS dementia in roughly 30% of those infected. Clinical neurologic disease with motor, cognitive, and behavior deficits results from profound CNS dysfunction. Autopsy findings of AIDS patients with dementia reveal marked loss of cortical neurons and cerebral atrophy. Numerous neurotoxic ag |
| 332-W | Transient Up-Regulation of HTLV-I following Co-Infection with SIV-I in the Nonhuman Primate. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 332-W Traina-Dorge V, Cunningham M, Martin L, Elbert G, Beilke M; Tulane Regional Primate Res. Ctr., Covington, LA BACKGROUND: HTLV-I is an important pathogen worldwide causing a life-long chronic infection that may lead to adult T-cell leukemia/ lymphoma (ATLL) and a variety of neuromuscular diseases. In certain geographic regions, co-infection in HIV-I positive individuals is high (5-10%), and is hypothesized to increase HTLV vir |
| 333-W | Rev-Independent SIV as Model to Study Pathogenic Mechanisms in Neonatal and Juvenile Rhesus Macaques Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 333-W von Gegerfelt A, Liska V, Marthas M, McClure H, Montefiori D, Li P, Markham P, Miller N, Ruprecht R, Felber BK NCI, NIH, Frederick, MD BACKGROUND: The viral protein Rev is the key viral factor essential for the export of the subset of unspliced and partially spliced lentiviral mRNAs and the production of structural proteins. Rev and its RNA binding site RRE can be replaced in both HIV and SIV by the constitutive RNA transport element CTE of the simian |
| 334-W | Development of a Murine Model for HIV Infection. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 334-W Soos T, Bitton N, Kewal-Ramani V, Littman DR; Skirball Inst. for Biomolecular Med., New York Univ. Med. Ctr., NY BACKGROUND: The development of a murine model to study HIV pathogenesis would significantly advance our understanding of HIV replication in vivo, the immune response to infection as well as aid in new approaches to treat or prevent HIV infection. However, mice are resistant to HIV infection, as species-specific blocks |
| 335-W | Importance of the Thymus toward Disease Progression in SIV-Infected Macaques Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 335-W Muthukumar A, Douek DC, Wozniakowski A, Ware F, Hirsch V, Johnson RP, Koup RA, Sodora DL; Univ. of Texas, Southwestern Med. Ctr., Dallas BACKGROUND: The thymus is responsible for de novo production of CD4+ and CD8+ T cells, and therefore is important for T-cell renewal. SIV infection of macaques, as well as HIV infection of humans, can result in thymic atrophy, suggesting a decrease in T-cell production. Here we assess thymic function by measuring the l |
| 336-W | Host Factors Controlling Simian Immunodeficiency Virus (SIV) Production from Rhesus Macaque CD4+ T Lymphocytes in Vitro and Disease Progression in Vivo Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 336-W A. Hartman*, P. Rajakumar, and M. Murphey-Corb Our results show that there is a 1-log difference in the susceptibility of cells from high and low producers to infection. Whether this can account for the differences in in vitro virus production as well as in vivo survival remains to be determined. We are currently performing a series of molecular analyses using real-time PCR to determine whether the block in infection occurs pre- or post-entry. This work is significant because we are identifying host factors that influence susceptibility of cells to infection with SIV. Ultimately, we hope to determine the host factors that contribute to differences in disease progression rates which can then be used to develop new therapies and vaccines. |
| 337-W | R5 HIV-1 Patient Isolates are Pathogenic in Fetal Thymic Organ Culture. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 337-W Choudhary S, Chernauskas D, Kwa D, Schuitemaker H, Camerini D; Univ. of Virginia, Charlottesville BACKGROUND: HIV-1-seropositive individuals can be divided into 2 categories, progressors, who develop AIDS within 8-10 years of seroconversion and long-term non-progressors (LTNP) who are asymptomatic > 10-12 years after seroconversion. Disease progression in 50% of cases of clade B HIV-1 infection is accompanied by th |
| 338-W | Deleterious Effect of Syncytium-Inducing (SI) CXCR4 Using HIV-1 Variants Is Directed at the Thymus and the Peripheral T-Cell Pool. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. Hazenberg M, Otto S, Hamann D, Roos M, Schuitemaker H, de Boer R, Miedema F; CLB/Sanquin and Landsteiner Lab. of the Academic Med. Ctr., Univ. of Amsterdam BACKGROUND: The emergence of syncytium-inducing (SI) / CXCR4 (X4) using HIV-1 variants is associated with accelerated CD4+ T-cell decline that could be related to increased killing of peripheral blood T cells or impairment of thymic function or both. METHODS: We studied the effects of these variants on both mechanisms |
| 339-W | Viral Factors Influencing Mother-to-Infant Transmission of SIV through Milk. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 339-W Amedee AM, Lacour N, Ratterree M, Murphey-Corb M, Martin L; Louisiana State Univ. Hlth. Sci. Ctr., New Orleans BACKGROUND: Oral transmission of HIV through breast-feeding accounts for a substantial number of pediatric HIV cases in areas of the world where safe alternatives for infant feeding are not available. To decipher the mechanisms involved in transmission through milk, we have developed an animal model using SIV-infected |
| 340-W | Role of Host Cell Factors in AIDS Pathogenesis. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 340-W Agrawal L, Alkhatib G; Indiana Univ. Sch. of Med., Indianapolis BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) employs CD4 and a co-receptor, principally the CCR5 and/or CXCR4 chemokine receptors, for entry into host cells. The central role of CCR5 in HIV-1 transmission and pathogenesis has been high-lighted by the epidemiological and genetic identification of powerful dis |
| 341-W | Dendritic Cell-Mediated HIV Transmission Is Necessary for Virus Replication in Rapidly Turning over T Cells Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 341-W R. Gummuluru* and M. Emerman These results suggest that DC-mediated transfer of virus to T cells is the most efficient method of virus transmission, and that this virus transfer can occur in a DC-SIGN independent fashion. Finally, using these parameters, we have developed a novel in vitro DC-T cell co-culture system where infected cell half-life is 2 days to mirror the kinetics of virus replication in vivo. |
| 342-W | IFN-alpha-Mediated Induction of CCR5 Leads to Expanded HIV-1 Tropism in Vivo Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 342-W Stoddart C, Keir M, McCune JM; Univ. of California, San Francisco BACKGROUND: HIV-1 binding and entry into target cells requires the expression of both CD4 and secondary chemokine receptors such as CXCR4 and CCR5. Previous studies demonstrate a critical role for HIV-1 co-receptor usage in viral pathogenesis. CCR5-utilizing (R5) viruses are efficiently transmitted and are normally fou |
| 343-W | Cellular Gene Transcription following Signaling through the Chemokine Receptors CCR5 and CXCR4 Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 343-W He H, van't Wout A, Bartz S, Lehrman G, O'Keeffe G, Emerman M, Bumgarner R, Mullins J; Univ. of Washington, Seattle BACKGROUND: Most HIV-1 variants can be divided into 2 groups based on chemokine co-receptor usage, with CCR5 and CXCR4 identified as co-receptors for HIV-1 R5 and X4 variants, respectively. These variants have biological significance, since emergence of X4 variants predicts more rapid disease progression. Signaling thr |
| 344-W | High Frequency of HIV Insertions Within and Adjacent to Regulatory Genes in Tissues Containing High Levels of p24 Expressing Macrophages. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 344-W Mack KD, Jin X, Kapp L, Wei R, Abbey N, Elbaggari A, Johnson R, Liu Y, Herndier B, McGrath MS; While at SLIL BioMed. Corp., Menlo Park, CA BACKGROUND: Retroviral insertional mutagenesis of specific host cell genes frequently induces neoplasias and neurodegenerative syndromes in animals. HIV infection is linked to the induction of dementia and lymphoproliferative disorders, yet the mechanisms critical to the induction of pathogenesis remain undefined. Here |
| 345-W | Survival in Relation to Virus Type, CD4 Count, and Plasma Virus Load in HIV-Infected Patients in Gambia, West Africa. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 345-W Alabi SA, Blanchard T, Shabbar J, Corrah T, Schim M, Ariyoshi K, Berry N, Whittle H; MRC Labs., Banjul, Gambia BACKGROUND: HIV-1 and HIV-2 are endemic in West Africa and the incidence of dual infection with both viruses is on the increase. Infection with HIV-1 is believed to be more severe than with HIV-2 in the majority of cases, while studies conducted mainly in the West have shown both baseline plasma virus load and CD4 coun |
| 346-W | The Relationship of Steady-State Plasma HIV-1 RNA Concentration and ex Vivo HIV-1 Replication Rate Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 346-W Connick E, Kocsis KS, Campbell TB; Univ. of Colorado Hlth. Sci. Ctr., Denver BACKGROUND: To determine the contribution of HIV-1 replication rate to steady-state plasma HIV-1 RNA concentration in subjects who are not receiving antiretroviral therapy. METHODS: 14 subjects enrolled in a study of the effects of antiretroviral therapy on HIV-1-specific immune responses in lymph nodes were evaluated. |
| 347-M | Early Development of Neutralizing IgA Antibodies in Serum of Primary HIV-1-Infected Patients Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 347-M Soderlund J, Broliden K, Mallet V, Maseruka H, Goh L, Andersson J; Karolinska Inst., Stockholm, Sweden BACKGROUND: This prospective study was aimed at characterizing the kinetics of long-term IgA responses in patients with acute HIV-1 infection receiving highly active antiretroviral therapy, HAART ( Combivir / Abacavir / |
| 348-M | Impact of Primary CMV Infection or Reactivation on HIV and Immunological Parameters in Patients With Primary HIV Infection (PHI) Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 348-M Goh L, Bernard MC, Lampe F, Janossy G, Cooper DA, Cunningham P, Andersson J, Capt A, Kinloch S, McDade H, Turkish S, Perrin L; GlaxoSmithKline, Greenford, UK BACKGROUND: Experimental and retrospective studies indicate a possible synergistic effect of CMV and HIV that may cause a more rapid disease progression. The aim of the present study was to investigate the impact of CMV infection/reactivation on HAART response during the first 28 weeks of treatment. METHODS: Plasm |
| 349-M | Analysis of HIV- and CMV-Specific Memory CD4 T-Cell Responses during Primary and Chronic Infections. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 349-M Harari A, Ellefsen K, Rizzardi GP, Ciuffreda D, Bart PA, Champagne P, Yerly S, Kaiser L, Perrin L, Pantaleo G; CHW, Lausanne, Switzerland BACKGROUND: HIV-1-specific CD4 helper, i.e. lymphoproliferative, T-cell responses are thought to be lost very early during HIV infection and recent studies have demonstrated that the preservation of these responses may be critical for the control of HIV-1 replication. However, even in the absence of lymphoproliferative |
| 350-M | Reduced CD4+ T-Cell Responses to Mitogen and Decreased Circulating CD123+ Dendritic Cells during Primary HIV-1 Infection. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 350-M J. Zaunders*1, D. Smith2, P. Grey2, M. Bloch3, R. Finlayson4, L. Goh5, A. D. Kelleher2, and D. A. Cooper2 Our results suggest that there is a dramatic decrease in the circulating pool of CD4 T cells capable of initiating an anti-HIV response, as well as a decrease in a key DC population. These changes occurred at a time when these cells were required to generate an optimal HIV-specific T-cell response. |
| 351-M | Activated CD8 Subsets and HIV-1 Viral Kinetics in Acute HIV-1 Infection Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 351-M Blattner WA, Oursler KA, Cleghorn F, Charurat M, Sill A, Bartholomew C, Jack N, Greenberg M, Tomaras G, LaBranche C, Weinhold K; Inst. of Human Virology, Baltimore, MD BACKGROUND: Emerging data from studies of acute HIV-1 seroconvertors suggest that immunologic and virologic interactions during the earliest phases of infection have a fundamental impact on HIV pathogenesis. Among 20 acute infection cases from the Trinidad Seroconvertor Cohort ascertained since October 1993 detaile |
| 352-M | Preferential and Persistent Depletion of CCR5+ Th Lymphocytes with Non-Lymphoid Homing Potential in Primary HIV Infection Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 352-M R. Krzysiek*1, A. Rudent 2, A. Lafeuillade4, D. Ingrand2 , D. Sereni3, P. Galanaud1, L. Grangeot-Keros2, and D. Emilie1 for the ANRS O86 PRIMOFERON A Study group HIV preferentially targets a specific subpopulation of TH lymphocytes with non-lymphoid homing potential early expressing CCR5 during PHI, inducing its persistent depletion despite virological response and stable restoration of the total pool of CD4+ T cells in the periphery. Since protective immunity in vivo mainly depends on TH lymphocytes carrying homing capacity to non-lymphoid tissues, our data may explain the persistent abnormalities of immune functions, including HIV-specific T cell responses, observed in HIV-infected patients. |
| 353-M | HIV-1 Variants in Body Fluids during Primary HIV Infection: Findings from the Duke-UNC-Emory Acute HIV Consortium. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 353-M Shugars DC, Freel S, Ritola K, Pilcher C, Fiscus SA, Giner J, Menezes P, Dean B, Patrick E, Robertson K, Hart CE, Swanstrom R, Lennox JL, Hicks C, Eron JJ Jr; Univ. of North Carolina, Chapel Hill BACKGROUND: Initiation of HIV infection by a single viral strain has been proposed to occur. We sought to investigate this hypothesis by characterizing the HIV-1 variants present in body fluids during human primary infection. METHODS: Prior to initiation of antiretroviral therapy, blood plasma (BP), and another body fl |
| 354-M | During Primary HIV Infection, HIV Replicates in HLA-DR- CD4+ T Lymphocytes as Actively as in HLA-DR + Fraction Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 354-M N. Ngo-Giang-Huong*1, J. Van-Grevenynghe1, J. M. Doisne2, C. Deveau3 , M. Sinet2, A. Venet2, and C. Rouzioux1 for the PRIMO Cohort Study Group The DR- CD4+ T cell compartment contributes to a large part of the systemic infection at time of primary HIV-1 infection. Moreover, HIV replicates in DR(-) CD4+ T cells as actively as in DR+ CD4+ T cells. |
| 355-M | Distinct Patterns of HIV-1 Evolution in CD14+ Monocytes and CD4+ T Lymphocytes between Patients with and without HAART. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 355-M Fulcher J, Hwangbo Y, Mullins J, Corey L, Zhu T; Univ. of Washington Sch. of Med., Seattle BACKGROUND: We have recently shown that HIV-1 replicates in CD14+ monocytes in vivo. As part of our continuing efforts to define the roles that blood monocytes may play in the establishment and persistence of HIV-1 infection, we have characterized HIV-1 sequences in CD14+ monocytes, as well as blood plasma and CD4+ T c |
| 356-M | HIV-1 Evolutionary Dynamics in a Dually Infected HIV-1 Patient Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 356-M Li F, Shankarappa R, He X, He H, Nickle D, Jensen M, Mittler J, Margolick JB, Mullins J; Univ. of Washington, Seattle BACKGROUND: HIV-1 co-infected AIDS patients provide a unique approach to understand the biological and molecular interactions of multiple strains, as well as the impact on the disease outcome. It is commonly thought that the maintenance of multiple lineages through time is due to diversifying selection. We tested this |
| 357-M | Genetic Variation in p6gag in Primary HIV Infection Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 357-M Smith D, Little SJ, Daar ES, Koup R, Hellmann NS, Dawson K, Wong JK, Richman DD, Leigh Brown AJ; Univ. of California, San Diego BACKGROUND: In primary HIV infection the viral population has little or no sequence diversity in the env gene within patients, but some variability has been noted in gag. It has recently been shown that duplications of a tripeptide APP motif in the p6gag region (the packaging signal for reverse transcriptase [RT]) may |
| 358-M | Quasi-Species Expansion without Adaptive Evolution in Seronegative S-HIV-Infected Macaques. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 358-M Shapiro S, Hsu M, Harouse J, Cheng-Mayer C, Balfe P; Aaron Diamond AIDS Res. Ctr., Rockefeller Univ., New York, NY BACKGROUND: Serial blood-bone marrow transfer of the R5-tropic SHIV(SF162) in 4 pairs of naïve macaques was performed during their seronegative window period (2 weeks post exposure). Increased replication of the virus was observed with each successive in vivo passage, with one animal in the passage 3 group (T353) rapid |
| 359-M | Real-Time, Universal Screening for Acute and Early HIV Infection in a Routine HIV Counseling and Testing Population Using Multistage Pooling and RNA PCR: Cost-Effective, Specific, and Feasible Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 359-M Pilcher C, McPherson JT, Leone PA, Peace-Brewer AL, Hicks C, Eron JJ, Fiscus SA; Univ. of North Carolina, Chapel Hill BACKGROUND: We assessed the feasibility of prospective, universal screening for acute HIV infection among patients presenting for routine HIV counseling and testing in North Carolina using HIV RNA PCR and multistage pooling. METHODS: Consecutive sera collected in North Carolina over 4 days were tested by OTC HIV-1 EIA |
| 360-M | Delayed Diagnosis of Primary HIV Infection after Presentation to the Health Care System. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 360-M Weintrob A, Giner J, Patrick E, Lennox J, Menezes P, Pilcher C, Eron JJ, Hicks C; Duke Univ., Durham, NC BACKGROUND: Many patients with primary HIV infection (PHI) are symptomatic with a viral syndrome ; however, the diagnosis of PHI is seldom made. METHODS: We analyzed 28 patients diagnosed with PHI between 1998 and August 2001 who were enrolled in a clinical trial at Duke University, University of North Carolina, or Emo |
| 361-M | How Well Do Rapid HIV Tests Detect Seroconverters? Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 361-M Branson B, Meredith N, Mei J, Hannon H CDC, Atlanta, GA BACKGROUND: Several newer rapid HIV tests have become available that are easy to perform, require little technical expertise, and provide results in 20 minutes or less. This study was conducted to evaluate the sensitivity of these newer rapid HIV tests for detecting seroconverters, compared with the EIA and Western blo |
362-M | Clinical Impact of Highly Active Antiretroviral Therapy Initiated Early after Primary HIV-1 Infection. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 362-M Lamontagne F, Costagliola D; INSERM SC4, Paris, France BACKGROUND: The clinical benefit of primary infection treatment remain unknown. METHODS: Data from the French Hospital Database on HIV infection of 661 HIV-1-positive subjects with documented date of infection were analysed to assess the clinical impact of potent early antiretroviral therapy. The progression to AIDS of |
| 363-M | Treatment of Acute and Early HIV-1 Infection in 132 Subjects with PI-Based Regimens Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 363-M Hogan C, Hurley A, Louie M, Captan B, Chung C, Zhang L, Ho D, Markowitz M; Aaron Diamond AIDS Res. Ctr., Rockefeller Univ., New York, NY BACKGROUND: Optimal management of primary and early HIV-1 infection has not been established. METHODS: We have treated 132 individuals during acute and early HIV-1 infection with open-label, PI-based HAART. Subjects had measurable HIV-1 RNA levels and absent or evolving HIV-1 serologies. All but 3 subjects had symptoms |
| 364-M | Treatment Effect on Plasma IL-7 and IGF-1 Levels and on Thymic Output in Patients with Acute/Early HIV Infection (AEI). Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 364-M Routy JP, Sylvestre M, Boulassel R, Poulin JF, Conway B, Sekaly RP, Cheynier R; McGill Univ., Montreal, QC BACKGROUND: HIV-infected patients have been shown to have an inverse correlation between IL-7 levels and CD4 cell depletion. We have shown that plasma IL-7 levels are elevated in patients infected over the previous 6 months when compared to controls (mean 15,4 [5,1-28,3] pg/mL vs 1.8 [0.4-3.6] pg/mL, p |
| 365-M | Relationship between Seminal and Plasma Viral Loads among Persons with Primary HIV Infection Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 365-M Kahn J, Hecht F, Warmerdam M, Liu L, Grant RM; Univ. of California, San Francisco BACKGROUND: Recently infected persons may be more infectious to sexual partners if viral load in genital secretions is high during primary viremia, as it is in blood. Semen viral load may rise with plasma viral load, or sometime thereafter. We evaluated baseline and serial samples of plasma and semen from newly infecte |
| 366-M | Estimating Transmission Probabilities over Time in Acute HIV Infection from Biological Data Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 366-M C. Pilcher*1, H. Tien1, P. Stewart1, P. Vernazza2, H. Chakraborty3, J. J. Eron1, and M. Cohen1 Susceptible partners of individuals with acute HIV infection may be at 20-fold greater risk per exposure compared to partners of individuals at virologic set point due to higher HIV shedding in semen. |
| 367-M | Will Transmission of Drug Resistant HIV be Driven by Individuals Infected with Drug Resistant Strains? Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 367-M A. J. Leigh Brown*1,2, S. D. W. Frost1, W. C. Mathews1, N. S. Hellmann3, E. S. Daar4, D. D. Richman1, and S. J. Little1 Based on this model, transmitted drug resistance will continue to increase, and individuals newly infected with TR will become the major source of new resistant infections, indicating an urgent need for interventions to reduce transmission. |
| 368-M | Transmission and Transmissibility of Drug Resistant HIV-1 Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 368-M R. M. Grant*1,2, J. Kahn2, M. Warmerdam1, L. Liu2, C. J. Petropoulos3, N. S. Hellmann3, and F. Hecht2 Primary drug resistance is highly prevalent and rising in San Francisco, especially for NNRTI-resistant HIV-1. Transmissibility of drug resistant HIV-1 likely reflects replication capacity, partial viral load responses during resistant viremia, and/or tropism for genital tissues. |
| 369-M | Survey of Genotypic Drug Resistance and Molecular Epidemiology of Virus from Patients with HIV-1 Primary Infection in 2000 in France Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 369-M Chaix ML, Descamps D, Harzic M, Schneider V, Deveau C, Pellegrin I, Tamalet C, Masquelier B, Rouzioux C, Meyer L, Brun-Vezinet F, Costagliola D, The ANRS AC11 Resistance Group Cohort PRIMO and PRIMSTOP Study Groups; Hosp. Necker, Paris BACKGROUND: Our objective was to survey the evolution of the prevalence of virus with genotypic antiretroviral resistance among French patients who presented with HIV primary infection during the year 2000. METHODS: Pre-treatment plasma samples were tested for genotypic resistance at time of acute infection in 98 patie |
370-M | No Increase in Protease Resistance and a Decrease in Reverse Transcriptase Resistance Mutations in Primary HIV-1 Infection: 1992-2001 Sydney, Australia Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 370-M Ammaranond P, Cunningham P, Oelrichs R, Suzuki K, Harris C, Leas L, Grulich A, Kelleher AD, Cooper DA; NCHECR, Univ. of New South Wales, Sydney BACKGROUND: Our objective was to describe epidemiological correlates of changes in prevalence of drug resistance mutations in patients with acute HIV-1 primary infection in Sydney, Australia . METHODS: 135 patients who had acute primary infection diagnosed between April 1992 and October 2001 and who had sterile plasma |
| 371-M | Decline in the Rate of Genotypic Resistance to Antiretroviral Drugs in Recent HIV Seroconverters in Spain Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 371-M de Mendoza C, del Romero J, Rodriguez C, Corral A, Soriano V; Inst. de Salud Carlos III and Ctr. Sandoval, Madrid, Spain BACKGROUND: Resistance to antiretroviral drugs represents one of the major obstacles for the success of HIV therapy. Viruses carrying drug-resistant mutations can be transmitted and, then, compromise the response to therapy in drug-naïve individuals. METHODS: We have compared the rate of primary mutations associated to |
| 372-M | Prevalence of Mutations Associated with Antiretroviral Drug Resistance among Recently Diagnosed Persons with HIV, 1998-2000 Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 372-M D. Bennett *, I. Zaidi, W. Heneine, T. Woods, G. García-Lerma, J. Kaplan, H. Weinstock for the Sentinel Surveillance for Variant, and Drug-Resistant Strains of HIV Study (SSVRS) Teams An increase in ARVDR prevalence among persons with newly diagnosed HIV was observed between 1998 and 1999 in 5 cities. Transmission of ARVDR-resistant strains may increase as treatment becomes more common, although prevalence will also vary depending on treatment outcomes and the success of risk reduction measures. Further multiyear studies in the same geographic areas are needed to evaluate whether the increase will continue or stabilize. |
| 373-M | Prevalence of HIV-1 Drug-Transmitted Resistance in Semen of Patients on HAART with Acute Sexually Transmitted Infections. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 373-M Taylor S, Sadiq T, Kaye S, Workman J, Cane P, Bennet J, Johnstone R, Byrne P, Copas A, Drake S, Weller I, Pillay D; PHLS, Univ. of Birmingham BACKGROUND: In previous studies, sexually transmitted infections (STI s) appear to increase seminal HIV-1 shedding in antiretroviral naïve individuals. Conversely, HAART appears to reduce seminal shedding of HIV-1. However, previous published studies have not investigated the effect of STI s on seminal shedding of HIV- |
| 374-M | Identification of a Transmission Chain of Drug-Resistant HIV-1. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 374-M Taylor S, Cane P, Workman J, Drake S, Shamanesh M, Pillay D; PHLS, Univ. of Birmingham BACKGROUND: There is evidence for an increasing prevalence of transmitted drug-resistant HIV-1 in Europe and the U.S. However, the overall impact of this phenomenon on the spread of resistance within the community as a whole is, to some extent, dependant on the stability of these viruses within the plasma of infected i |
| 375-M | First Report of Multi-Drug Resistant HIV-1 in Southern Africa. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 375-M Miller S, Peters D, Keena L; Innovir Inst., Johannesburg, South Africa Introduction: There is a dearth of information on the prevalence of antiretroviral resistance in Africa. Previously, financial constraints limited the use of maximally suppressive regimens. Substantial reductions in drug costs have recently been implemented that substantially improve access to potent antiretroviral the |
| 376-M | Infectivity and in Vitro Replication of Sexually Transmitted Drug-Resistant HIV-1 Variants Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 376-M Simon V, Vanderhoeven J, Hurley A, Mizuno H, Padte N, Horowitz A, Markowitz M; Aaron Diamond AIDS Res. Ctr., Rockefeller Univ., New York, NY BACKGROUND: It has been assumed that drug-resistant viruses are in general less replication-competent than wild types. However, these viruses are transmissible. To assess the properties of transmitted, drug-resistant HIV-1, we characterized primary isolates derived from subjects found to be newly infected with viruses |
| 377-M | Replicative Fitness of MDR Viruses in Primary HIV-1 Infection. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 377-M Petrella M, Brenner B, Routy JP, Moisi D, Oliveira M, Detorio M, Spira B, Conway B, Lalonde R, Sekaly RP, Wainberg MA; McGill AIDS Ctr., Lady Davis Inst., Montreal, QC, Canada BACKGROUND: Persistence of dual and triple class multidrug (MDR) resistant viruses acquired during primary HIV infection (PHI) may affect virological and treatment outcomes. This study compares the genotypic evolution and fitness of MDR and wild-type viruses present in PHI. METHODS: Longitudinal sequence analysis was p |
378-M | Memory CD4+ T Cells Are the Earliest Detectable HIV-1-Infected Cells in the Female Genital Mucosal Tissue during HIV-1 Transmission in an Organ Culture System Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 378-M P. Gupta*1, K. Collins1, D. Dampf1, D. Landers1, G. Naus1, and B. Patterson2 This finding provides an alternative pathway for the dissemination of infection to the body in which early infection of T cells in genital mucosa would allow virus to expand rapidly and get transferred to the dendritic cells, which would then carry HIV-1 to draining lymph nodes. The study also indicates the utility of the organ culture to screen topical microbicides for their ability to block sexual transmission of HIV-1. |
| 379-M | Recovery of Infectious Human Immunodeficiency Virus Type-1 (HIV-1) from the Oropharynx: Implications for Oral Transmission of HIV-1. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 379-M Celum C, Collis TK, Whittington W, Sanchez J, Lucchetti A, Lockhart D, Dithmer-Schreck D, Zuckerman R, Sampoleo R, Harb S, Dragavon J, Coombs RW; Univ. of Washington, Seattle BACKGROUND: Oral-genital transmission of HIV-1 occurs and HIV-1 RNA can be detected in the saliva; however, culture of HIV-1 from the saliva has been generally unsuccessful ( |
| 380-T | A Virus/Cell-Based Assay for the Discovery of Novel Anti-HIV-1 Compounds. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 380-T Adelson M, Pacchia A, Kaul M, Rando R, Peltz S, Ron Y, Dougherty JP; UMDNJ, Piscataway BACKGROUND: Due to the great propensity of HIV-1 to mutate, the adverse side-effects associated with the current class of HIV-1 antivirals, the lack of an effective vaccine, and a continuing growth in the worldwide infection rate, the search for additional therapies for AIDS has been of the highest priority. High throu |
| 381-T | Optimization of Multiple Factors in the Discovery and Development of Highly Potent and Broad Spectrum Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors for the Treatment of AIDS Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 381-T Das K, Arnold E, Clark AD Jr, Ludovici DW, Kukla MJ, DeCorte B, Kavash RW, Andries K, Pauwels R, de Bethune MP, van't Klooster GA, Lewi P, Hughes SH, Janssen PA; Ctr. for Advanced Biotechnology and Med., Piscataway, NJ BACKGROUND: A multidisciplinary approach has led to the discovery of novel non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs) that show great promise for the treatment of AIDS. A combination of broad antiviral screening, metabolic studies, and analysis of 3-dimensional structure-activity relationships led t |
| 382-T | Combining Antilentiviral Transgenes Potentiates Inhibition of HIV. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 382-T Strayer D, Branco F, Landre J, BouHamdan M, Shaheen F, Pomerantz RJ; Jefferson Med. Coll., Thomas Jefferson Univ., Philadelphia, PA BACKGROUND: Unlike single drugs, combination antilentiviral chemotherapy targets several HIV functions at once. It thus minimizes the chance of escape mutation by the virus. We hypothesized that combining complementary anti-HIV transgenes would allow similar increased therapeutic efficacy in genetic therapy of HIV infe |
| 383-T | Targeting HIV Morphogenesis by Inhibiting p55 and gp160 Processing. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 383-T Cordelier P, Strayer D; Jefferson Med. Coll., Thomas Jefferson Univ., Philadelphia, PA BACKGROUND: Protein processing is required for HIV infectivity. Cellular trans-Golgi network (TGN) serine proteases (e.g., furin) cleave gp160 to gp120; HIV protease (PR) cleaves p55(Gag) to p24, etc., in budding virions. alpha1-antitrypsin (alpha1AT) is cleaved by serine proteases, causing their inactivation. alpha1AT |
| 384-T | In Vivo and in Vitro Characterization of GS 7340, an Isopropylalaninyl Phenyl Ester Prodrug of Tenofovir; Selective Intracellular Activation of GS 7340 Leads to Preferential Distribution in Lymphatic Tissues Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 384-T Lee W, He G, Mulato A, Delaney W, Eisenberg E, Cihlar T, Xiong S, Miller MD, Gill S, Shibata R, Gibbs C; Gilead Sci., Inc., Foster City, CA BACKGROUND: Tenofovir is an acyclic nucleotide analog which has potent in vitro and in vivo activity against HIV. Tenofovir disoproxil (TDF), an oral prodrug of tenofovir, is approved for the treatment of HIV. After oral administration of TDF, only tenofov |
| 385-T | DPC 817: A Cytidine Nucleoside Analog with Activity against AZT- and 3TC-Resistant Viral Variants Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 385-T Erickson-Viitanen S, Schinazi RF, Mellors J, Geleziunas R, Trainor G, Wu JT, Gallagher K, Klabe R, Otto M, Pierce M, Martin DE; Bristol-Myers Squibb Co., Wilmington, DE BACKGROUND: Nucleoside analog reverse transcriptase inhibitors (NRTIs) with improved activity against clinically relevant resistant viruses are needed to construct effective regimens for ARV-experienced individuals. DPC 817, beta-D-2 ,3 -didehydro-2 ,3 -dideoxy-5-fluorocytidine is a cytidine nucleoside analog that reta |
| 386-T | BCH-13520, a New Heterosubstituted Nucleoside Analogue, Is an Effective Inhibitor of Drug-Resistant HIV-1 Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 386-T Bethell RC, Allard B, De Muys JM, Gu Z, Guyen-Ba N, Ren C, Wainberg MA, McKenna P, Taylor DL; Shire BioChem Inc., Laval, QC, Canada BACKGROUND: The activity of BCH-13520, a new heterosubstituted nucleoside analog, against drug-resistant strains of HIV-1 has been determined, and in vitro selection studies have been performed to investigate the emergence of resistance to this drug candidate. METHODS: The antiviral efficacy of BCH-13520 was tested aga |
| 387-T | Water-Soluble Metalloporphyrins Represent Potent Inhibitors of HIV-1 Replication. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 387-T Argyris EG, Fang J, Pomerantz RJ; Dorrance H. Hamilton Labs., Jefferson Med. Coll., Thomas Jefferson Univ., Philadelphia, PA BACKGROUND: We have recently demonstrated by using phage peptide libraries as well as mutagenesis studies that metalloporphyrins, by binding to a novel and distinct site of HIV-1 reverse transcriptase (HIV-1 RT), which includes the 398-407 sequence from the connection subdomain of p66 subunit, inhibit enzymatic activit |
388-T | Generation of HIV Variants Resistant to 4'-Ethynyl-2'-Deoxynucleosides: A Role of T165 and M184 in Reverse Transcriptase (RT) Function. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 388-T Kodama E, Ikeuchi M, Matsuoka M, Mitsuya H; Inst. for Virus Res., Kyoto Univ., Japan BACKGROUND: Novel nucleoside analogs, 4 -ethynyl-2 -deoxynucleosides (4 -E-dNs), retain the 3 -OH moiety and exert potent activity against a wide spectrum of HIV including multi-drug resistant HIV variants. However, the mechanism of the anti-HIV action remains unclear. In this work, we generated HIV variants resistant |
| 389-T | 2-Quinolone Derivatives as Potential HIV NNRTI Agents. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 389-T Freeman G, Hopkins A, Andrews C III, Lowell G, Gonzales S, Cowan J, Schaller L, Koszalka G, Hazen R, Boone L, Ferris R, Creech K, Roberts G, Short S, Weaver K, Milton J, Stuart D, Stammers D, Chan J; GlaxoSmithKline, Res. Triangle Park, NC BACKGROUND: HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) are part of the combination therapy currently used to treat HIV infection. The features of a new NNRTI drug for HIV treatment must include selective potent activity against wild-type virus as well as potent activity against mutant virus that res |
390-T | Inhibition of HIV-1 Gene Expression by dsRNA-Mediated Interference. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 390-T Park WS, Kurosaki NM, Takaku H; Chiba Inst. of Technology, Japan BACKGROUND: The RNA interference (RNAi) phenomenon is a recently observed process in which the introduction of a double-stranded RNA (dsRNA) into a cell causes specific degradation of an mRNA containing the same sequence. To study dsRNA-mediated gene interference in HIV-1-infected cells, we have designed 6 longer dsRNA |
| 391-T | AMD-3100 CXCR4 Receptor Blocker Fails to Reduce HIV Viral Load by > 1 Log following 10-Day Continuous Infusion Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 391-T Hendrix C, Collier AC, Lederman M, Pollard R, Brown S, Glesby M, Flexner C, Bridger G, Badel K, MacFarland R, Henson G, Calandra G, The AMD-3100 HIV Study Group; Johns Hopkins Univ., Baltimore, MD BACKGROUND: AMD-3100 is a CXCR4 receptor blocker with anti-HIV activity; it was well tolerated in single-dose volunteer clinical studies of up to the highest dose of 80 mug/kg. The objective was to test the safety, pharmacokinetics (PK), and antiviral effect of AMD-3100 administered for 10 consecutive days by continuou |
| 392-T | Analysis of Patient-Derived HIV-1 Isolates Suggests a Novel Mechanism for Decreased Sensitivity to Inhibition by T-20 and T-649 Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 392-T Heil M, Decker J, Sfakianos J, Shaw G, Hunter E, Derdeyn C; Univ. of Alabama, Birmingham, AL BACKGROUND:. Peptide-based fusion inhibitors like T-20 interfere with conformational changes that normally promote HIV-1 membrane fusion by competitively binding to targets within the heptad repeat regions (HR1 an HR2) of gp41. Amino acid residues 36 - 38 within HR1 (GIV) define the level of sensitivity to T-20, but do |
| 393-T | T-20 and DAPD have Synergistic in Vitro Anti-HIV Interactions. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 393-T Tremblay C, Poulain D, Hicks JL, Giguel F, Kollmann C, Chou TC, Hirsch MS; Massachusetts Gen. Hosp., Boston File Not Found |
| 394-T | Identification of HIV-1 Fusion Inhibitors Derived from Synthetic Combinatorial Peptide Libraries. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 394-T Boggiano C, Blondelle SE; Torrey Pines Inst. for Molecular Studies, San Diego, CA BACKGROUND: The interactions between the viral envelope glycoprotein gp120, its cellular receptor CD4, and the specific co-receptor are part of the early events occurring during cell infection by HIV-1. Antagonists of HIV-1 replication at the entry level, via blockade of attachment, gp120/CD4/co-receptor interactions, |
| 395-T | In Vivo Evolution of X4 HIV-1 Variants in the Natural Course of Infection Coincides with Reduced Sensitivity to CXCR4 Antagonists. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 395-T van Rij RP, Visser JA, Naarding M, Schols D, Schuitemaker H; CLB-Sanquin and Landsteiner Lab., Academic Med. Ctr., Univ. of Amsterdam, The Netherlands BACKGROUND: Antagonists directed against the chemokine receptor CXCR4, the co-receptor for entry of syncytium-inducing (SI) HIV-1 into CD4+ cells, are successful inhibitors of SI HIV-1 infection in vitro and are considered for use as therapeutic drugs. We previously showed that early after their emergence in vivo, SI H |
| 396-T | HIV-1 Mutants Less Susceptible to SCH-D, a Novel Small-Molecule Antagonist of CCR5 Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 396-T Chen Z, Hu B, Huang W, He T, Huang Y, Strizki J, Xu S, Wojcik L, Whitcomb JM, Zhang L, Petropoulos CJ, Baroudy B, Ho D; Aaron Diamond AIDS Res. Ctr., Rockefeller Univ., New York, NY BACKGROUND: SCH-D is a small-molecule antagonist of CCR5 that is in preclinical development. The antiviral potency of SCH-D is superior to that of SCH-C, which is in clinical trials. The goal of this study is to understand the evolution of an R5-tropic HIV-1 under the selective pressure of SCH-D in vitro. METHODS: The |
| 397-T | Genotypic and Phenotypic Analysis of in Vitro Generated HIV-1 Escape Isolates to the CCR5 Antagonist SCH-C. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 397-T Riley J, Wojcik L, Xu S, Strizki J; Schering-Plough Res. Inst., Kenilworth, NJ BACKGROUND: SCH-C represents a new class of CCR5 antagonists that has potent antiviral activity against HIV-1 infection. This molecule binds to CCR5 and blocks the entry of HIV-1 isolates that uses this receptor for infection. Method: To investigate the potential mechanism of viral resistance to this CCR5 antagonist we |
| 398-T | Antagonism of the CCR5 Receptor by SCH-C Leads to Elevated beta-Chemokine Levels and Receptor Expression in Chronically Treated PBMC Cultures. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 398-T Xu S, Wojcik L, Strizki J; Schering-Plough Res. Inst., Kenilworth, NJ BACKGROUND: SCH-C, a CCR5 receptor antagonist, is a potent antiviral agent for R5-tropic HIV isolates and is being evaluated clinically. In this study we investigated the potential effects of CCR5 blockade on beta-chemokine production and receptor expression in vitro. METHODS: Human PBMCs were cultured in the presence |
| 399-T | Role of Co-Receptor Inhibitors in Blocking HIV-1 Primary Isolates in Vitro. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 399-T Citterio P, Bulgheroni E, Croce F, Lo Cicero M, Bagnarelli P, Galli M, Rusconi S; Univ. of Milan, Italy BACKGROUND: Different strategies in blocking HIV entry are being evaluated either by targeting one of the cellular receptors, CD4 or co-receptors, or the envelope proteins. The majority of available compounds interfere with the binding of gp120 with the co-receptor. These molecules are chemokine analogues, which interf |
400-T | Novel Low Molecular Weight Spirodiketopiperazine Derivatives Potently Inhibit R5 HIV-1 Infection through Their Antagonistic Effects on CCR5. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 400-T K. Maeda*1, K. Yoshimura1, S. Shibayama2, H. Habashita2, T. Miyakawa1, M. Aoki1, Y. Koh1, H. Nakata1, H. Tada2, K. Sagawa2 , D. Fukushima2, and H. Mitsuya1 These data warrant that spirodiketopiperazine derivatives are further developed as potential therapeutics for HIV-1 infection. |
| 401-T | PRO 542 (CD4-IgG2) has a Profound Impact on HIV-1 Replication in the Hu-PBL-SCID Mouse Model Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 401-T Franti M, O'Neill T, Maddon P, Burton DR, Poignard P, Olson W; Scripps Res. Inst., La Jolla, CA BACKGROUND: PRO 542 is a recombinant antibody-like fusion protein wherein the D1D2 domains of human CD4 are grafted onto the heavy and light chain constant regions of human IgG2. Unlike monovalent and divalent CD4-based proteins, tetravalent CD4-IgG2 broadly and potently neutralizes primary HIV-1 isolates. We have eval |
| 402-T | Identification of CCR5 Co-Receptor Inhibitors that Potently and Selectively Block HIV-1 Replication Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 402-T Olson W, Dragic T, O'Hara B, Nagashima K, Tsamis F, Westby M, Cammack N; Progenics Pharmaceuticals, Inc., Tarrytown, NY BACKGROUND: The CC-chemokine receptor CCR5 is a requisite fusion co-receptor for primary HIV-1 isolates. As a 7-transmembrane G-protein-coupled receptor with limited tissue distribution, CCR5 represents a promising target for a new class of viral entry inhibitors. High-throughput screens for inhibitors of chemokine bin |
| 403-T | The CCR5 Co-Receptor Inhibitor PRO 140 Effectively Controls Established HIV-1 Infection in Vivo Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 403-T Franti M, Nagashima K, Maddon P, Burton DR, Olson W, Poignard P; Scripps Res. Inst., La Jolla, CA BACKGROUND: The increasing incidence of multidrug-resistant HIV-1 mandates the search for novel classes of antiretroviral agents. CCR5 is a requisite fusion co-receptor for primary HIV-1 isolates and provides a promising target for antiviral therapy. PRO 140 is an anti-CCR5 monoclonal antibody that potently inhibits HI |
| 404-T | Reduction of Persistent HIV-1 Replication Using Cell-Reservoir Specific Anti-Retroviral Therapy. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 404-T Patterson B, Becker SL, Snidow J, Pobiner B, Grundhoefer D, Landay A; Children's Mem. Hosp., Chicago, IL. BACKGROUND: Minimization of persistent viral replication would slow viral evolution and reduce the chances of developing antiretroviral drug resistance mutations. We tested the hypothesis that monitoring persistent viral replication in cellular reservoirs would allow tailoring of HAART using agents specifically targeti |
| 405-T | Residual HIV-1 Disease Eradication (RHIDE) Trial: An HIV-1 Reservoir Eradication Approach in Humans Using a Novel and Stimulatory Intensification Therapy. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 405-T Pomerantz RJ, Otero M, Nunnari G, Malin A, Coates C, Dascenzo C, DeSimone J, Babinchak T, Zhang H, Dornadula G, Culnan D, Sullivan J, Xu Y, Stern J, Cavert W, Haase A, Kulkosky J; Thomas Jefferson Univ., Philadelphia, PA BACKGROUND: Highly active antiretroviral therapy (HAART) has led to significant changes in mortality and morbidity in the HIV-1 epidemic. Nevertheless, due to 2 main molecular mechanisms of viral persistence, namely cryptic viral replication and proviral latency in resting T-cells of replication- competent virus, HAART |
| 406-T | The Effect on Specific Human Primary Cell Populations of Prostratin, an Inducer of Latent HIV Reservoirs. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 406-T Kulkosky J, Sullivan J, Otero M, Culnan D, Xu Y, Pomerantz RJ; Thomas Jefferson Univ., Philadelphia, PA BACKGROUND: Prostratin is a non-tumor promoting phorbol ester which inhibits de novo human immunodeficiency virus type-1 (HIV-1) infection yet up-regulates expression of latent pro-viral DNA. The lack of tumor promotion, block of viral spread, yet ability to induce latent proviral expression, suggests prostratin could |
| 407-T | Course of HIV RNA in CD4+ and CD8+ Lymphocytes in HIV-Infected Patients Undergoing HAART as Determined by Ultrasensitive Fluorescence in Situ Hybridisation (UFISH) Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 407-T Rubbert A, Wohrmann A, Passon D, Jutte A, Salzberger B, Fatkenheuer G; Univ. of Cologne, Germany BACKGROUND: CD8+ T lymphocytes in HIV-infected patients have recently been shown to harbor HIV RNA. Little is known about how this viral reservoir within CD8+ lymphocytes responds to HAART-therapy. METHODS: PBMC were obtained from 20 HIV-infected patients before and after initiation of HAART at 3, 6, and 12 months and |
| 408-W | A Comparison of AZT/3TC vs 3TC/d4T and ddI/d4T in Combination with Efavirenz as First Line Therapy: Efficacy and Safety Results after 48 Weeks Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 408-W M. R. Domula*1, J. C. Wasmuth1, A. Jütte2, G. Fätkenheuer2, M. Oette3, A. Theisen3, C. Höhn4, H. Knechten4, B. Pfeil5, S. Fenske6, A. Rieke7, and J. K. Rockstroh1 Efavirenz plus 3TC/D4T or AZT/3TC or DDI/D4T proves to be an efficient first-line antiretroviral regimen. Treatment terminations due to polyneuropathy are higher in the D4T/DDI arm. Overall, termination due to adverse events, however, is low. |
| 409-W | Once-Daily vs Twice-Daily Kaletra (Lopinavir/Ritonavir) in Antiretroviral-Naive HIV+ Patients: 48-Week Follow-Up Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 409-W Eron JJ, Bernstein B, King M, Manning L, Bertz R, Beall G, Carpio-Cedraro F, Feinberg J, Horowitz H, Wheeler D, Kessler H, Mildvan D, Ruane P, Yangco B, Renz C, Mayer S, Sun E; Univ. North Carolina, Chapel Hill BACKGROUND: Kaletra is a coformulation of lopinavir (LPV), an HIV protease inhibitor, and ritonavir (r), which inhibits CYP3A, providing increased plasma levels of LPV. Clinical trials of LPV/r are ongoing in HIV+ pat |
| 410-W | CHARM: A Phase III Open-Label, Randomized, Multi-Center Study to Evaluate the Efficacy and Tolerability of Adding Nevirapine (NVP) and/or Hydroxyurea (HU) to a Triple Nucleoside-Based Antiretroviral Drug Regimen in Treatment-Naive HIV-1-Infected Subjects. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 410-W M. Beniowski*, R. Wood, G. Gray, A. Horban, R. Schmidt, A. Lazzarin, A. Lafeuillade, D. Paes, H. Carlier, D. Blanckenberg, E. van Weert, R. van Leeuwen, and J. Lange for the CHARM Trial Study Team Adding HU to a triple NRTI-regimen did not increase treatment success and led to a slower increase in mean CD4-count. Adding NVP led to a more rapid decay in plasma HIV-1 RNA level, but increased the incidence of presumed HSR to NVP or ABC. |
| 411-W | Stavudine XR vs Stavudine IR as Part of Potent Antiretroviral Combination Therapy: 24-Week Safety and Antiviral Efficacy Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 411-W Pollard R, Ive P, Farthing C, Whelden M, Thompson S, Brett-Smith H; Univ. of Texas Med. Branch, Galveston BACKGROUND: This mutinational, prospective, randomized, double-blind, double-dummy study was designed to evaluate the antiviral activity, safety, and tolerability of once-daily d4T extended-release (XR) compared to the currently available twice-daily formulation of d4T immediate release (IR) when each is combined in a |
| 412-W | Antiviral and Immunological Effects of Hydroxyurea (HU) plus HAART vs HAART Alone in Peripheral Blood and Lymphoid Tissue. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 412-W Stellbrink HJ, van Lunzen J, Frahm N, Jessen H, Adam A, Weitner L, Plettenberg A, Stoehr A, Dalhoff K, Kuhlmann B, Hoffmann C, Horst H, Fenske S, Tenner-Racz K, Racz P; Univ. Hosp. Eppendorf, Hamburg BACKGROUND: Hydroxyurea (HU) could have the potential of decreasing the number of target cells for HIV replication and reducing viral integration. We tried to further characterize its effects on CD4+ T-cell activation, CCR-5 expression, and proliferation in peripheral blood and lymphoid tissue as well as on productive |
| 413-W | Tenofovir DF: A 48-Week Final Analysis from a Phase III Randomized, Double Blind Placebo Controlled Study in Antiretroviral Experienced Patients Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 413-W K. Squires*1, G. Pierone2, D. Berger3, C. Steinhart4, N. Bellos5, S. L. Becker6, S. S. Chen7, M. D. Miller7, D. F. Coakley7, and A. Cheng7 for the Study 907 Team Through 48 weeks, once-daily tenofovir DF 300 mg provides durable antiviral suppression in treatment experienced patients. In addition, tenofovir DF has a safety profile which remains similar to placebo. |
| 414-W | Final 48-Week Genotypic and Phenotypic Analyses of Study 907: Tenofovir DF (TDF) Added to Stable Background Regimens Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 414-W Margot NA, Johnson A, Cheng A, Coakley DF, Miller MD; Gilead Sci., Inc., Foster City, CA BACKGROUND: Study 907 was a phase III study evaluating TDF when added to stable background regimens in treatment-experienced patients. The first 24 weeks were placebo-controlled (2:1), followed by 24 weeks of open-label TDF. 94% of patients had baseline NRTI resistance mutations. At week 24, there was a significant mea |
| 415-W | The Viread Expanded Access Program (EAP): Safety and Efficacy of Tenofovir Disoproxil Fumarate (TDF) in Antiretroviral Treatment (ART)-Experienced Patients Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 415-W S. Follansbee*1, J. Reynes2, M. Nelson3, B. Clotet4, A. Lazzarin5, A. Adam6, S. Van Doren7, R. Buffels7, S. Barriere7, L. Zagury7, I. Miranski7, and J. Rooney7 Data from ART-experienced patients treated with TDF in the global EAP are consistent with that observed in controlled clinical trials of TDF. |
| 416-W | Safety Profile of Tenofovir DF in Antiretroviral-Experienced Patients from Randomized, Double-Blind, Placebo-Controlled Clinical Trials. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 416-W Cheng A, Barriere S, Coakley DF, Chen SS, Wulfsohn M, Toole JJ; Gilead Sci., Inc., Foster City, CA BACKGROUND: Tenofovir DF (TDF) is a single-tablet once-daily nucleotide reverse transcriptase inhibitor (NRTI) with activity against wild type and nucleoside resistant HIV. METHODS: Adverse event (AE) and laboratory data were pooled and analyzed from 2 |
| 417-W | A Week-48 Assessment of High Strength T-20 Formulations in Multi-Class Experienced Patients Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 417-W Wheat LJ, Lalezari J, Kilby M, Wheeler D, Salgo M, DeMasi R, Delehanty J; Indiana Univ., Indianapolis BACKGROUND: The initial 50 mg/mL T-20 carbonate (CO3) formulation required 2 injections BID to deliver a dose of 90 mg BID. High-strength (100 mg/mL) CO3 and TRIS formulations have been developed to reduce the number of daily injections. METHODS: This sequential, cross-over study compared the initial T-20 50 mg/mL CO3 |
| 418-W | A Week 48 Assessment of a Randomized, Controlled, Open-Label Phase II Trial (T20-206) Evaluating 3 Doses of T-20 in PI-Experienced, NNRTI-Naive Patients Infected with HIV-1 Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 418-W Lalezari J, DeJesus E, Northfelt D, Richmond G, Delehanty J, DeMasi R, Salgo M; Quest Clin. Res., San Francisco, CA BACKGROUND: T-20 is the first of a new class of antiretrovirals called HIV-1 fusion inhibitors and is in phase III trials. Prior studies focused on the use of T-20 in highly treatment-experienced patients. T20-206 enrolled less-experienced, NNRTI-naïve patients. METHODS: 71 protease inhibitor (PI)-experienced patients |
| 419-W | The Effect of Different HAART Regimens on Slope of Viral Rebound in HIV-Infected Patients Failing Therapy. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 419-W Press N, Woods R, Raboud J, Harrigan PR, Montaner JG, The INCAS AVANTI and CNAAB3005 Study Teams; Canadian HIV Trials Network, Vancouver, BC, Canada BACKGROUND: The purpose of this study was to compare the characteristics of virologic rebounds in HIV-1-infected patients on various HAART regimens. METHODS: Individual patient data were compared from the triple regimen arms of 4 completed clinical trials ( INCAS: AZT /ddI/NVP, n=51; AVANTI-2: A |
| 420-W | Pharmacokinetic Parameters and Virological Response to the Combination of Lopinavir/Ritonavir (LPV/r) and Amprenavir (APV) in HIV-Infected Patients with Multiple Treatement Failures: Week-6 Results of Puzzle 1-ANRS Study Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 420-W G. Raguin*1, A. M. Taburet2, G. Chêne3, L. Morand-Joubert4, C. Droz3, C. Le Tiec2, F. Clavel5, and P. M. Girard4 for the Puzzle 1 Study Group In patients having failed multiple lines of treatment, salvage with APV combined to LPV/r and RTV showed significant virological response despite a PK interaction between LPV and APV. |
| 421-W | Virological and Immunological Benefit of a Salvage Therapy that Includes Kaletra plus Fortovase Preceded or not by Antiretroviral Therapy Interruption (TI) in Advanced HIV-Infected Patients (6-Month-Follow-up) Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 421-W Ruiz L, Ribera E, Bonjoch A, Martinez-Picado J, Diaz M, Romeu J, Marfil S, Negredo E, Garcia-Prado J, Tural C, Puig T, Sirera G, Clotet B; IrsiCaixa Fndn., Badalona, Spain Objective: Our objective was to assess in a prospective, open, randomised study the virological efficacy of a Mega-HAART salvage therapy which includes Kaletra + Fortovase + 3TC +ABC+ddI, precede |
| 422-W | Indinavir TID vs Indinavir/Ritonavir BID in Combination with AZT/3TC for HIV Infection in Nucleoside Pretreated Patients: HIV-NAT 005 76-Week Follow Up. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 422-W Boyd M, Duncombe C, Ruxrungthram K, Khongphattanayothin M, Hassink E, Srasuebkul P, Sangkote J, Reiss P, Stek M, Lange J, Cooper DA, Phanuphak P; HIV-NAT, Thailand BACKGROUND: Use of IDV may be simplified by addition of RT BID dosing and removes need for dietary restrictions. There are limited randomised data on IDV/RTV BID compared to TID dosing. METHODS: In this ongoing, prospective, randomised, open label study 106 patients were randomised to either IDV 800 mg (TID) or IDV 800 |
| 423-W | A Prospective Study of Deep Salvage Therapy with Lopinavir/r, Amprenavir, and NRTIs: Final 24-Week Data, Pharmacokinetics, and Association of Drug Levels/Drug Susceptibility with Virologic Response Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 423-W Baldini F, Rizzo MG, Hoetelmans R, Murri R, Di Giambenedetto S, Cingolani A, Cauda R, De Luca A; Catholic Univ., Rome, Italy BACKGROUND: Patients showing virologic failure to available antiretroviral classes have few residual treatment options. Lopinavir (LPV)/r and amprenavir (APV) show less cross resistance to other protease inhibitors (PI) but preliminary retrospective studies have shown negative pharmacokin |
424-W | The HYDILE Trial: A Quadruple Combination of Nucleoside Analog Hydroxyurea and IL-2 as Salvage Therapy for HIV Infection. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 424-W Lafeuillade VA, Hittinger G, Chadapaud S, Poggi C; Toulon, France BACKGROUND: Our objective was to evaluate the efficacy of a RTI regimen, with or without hydroxyurea (HU) and interleukin-2 ( IL-2 ), in HIV-infected patients failing PI-containing regimens. METHODS: Randomized study comparing D4t + ddI + abacavir + |
| 425-W | ACTG 364: Efficacy of Nelfinavir (NFV) and/or Efavirenz (EFV) in Combination with New NRTIs in Nucleoside Experienced Subjects: Week-144 Results. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 425-W Albrecht MA, Bosch RJ, Liou SH, Katzenstein D; Beth Israel Deaconess Med. Ctr., Boston, MA BACKGROUND: The optimal alternative therapy for subjects with NRTI experience who develop viral rebound remains uncertain. ACTG 364 examined long-term virologic and immune responses of quadruple vs triple antiretroviral therapy (ART) regimens in exclusively NRTI-treated subjects. This was a randomized, partially-blind |
| 426-W. | Virologic Activity of Efavirenz in Subjects who Experienced Virological Failure with Emivirine (EMV, MKC-442) Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 426-W Borroto-Esoda K, Sanne I, Andrews S, Kelbe C, Naiker P, Sole T, Anderson J, Harris J, Kargl D, Painter G, Rousseau F, Moxham C; Triangle Pharmaceuticals Inc., Durham, NC BACKGROUND: In vitro resistance studies have shown that HIV containing non-nucleoside reverse transcriptase (NNRTI) mutations other than K103N are sensitive to inhibition by efavirenz (EFV). Emivirine is a potent NNRTI that has a low incidence of K103N mutation when given in combination with lamivudine. |
| 427-W | Virological Response to Salvage Therapy at 6 Months in Patients with B or Non-B Subtypes Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 427-W P. Hermans*1, J-C. Schmit2, K. Kabeya1, E. O'Doherty1, S. De Wit1, B. Sommereijns1, and N. Clumeck1 This study suggests that virological response to therapy is similar in patients carrying B and non-B clades. |
| 428-W | Racial Differences in Clinical Efficacy of Efavirenz-Based Antiretroviral Therapy Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 428-W Wegner S, Vahey M, Dolan M, Wallace M, Aronson N, Barile A, Emmons W, Frazier S, Stephan K, Nau M, Piscitelli S, Harrigan R, Larder B; U.S. Military HIV Res. Prog., Rockville, MD BACKGROUND: Different cytochrome P450 (CYP) 2D6 genotypes have been shown to predict marked difference in efavirenz (EFV) trough levels. CYP genotypes have different frequencies in different ethnic and racial groups. We sought to assess the relative clinical response duration in African American (AA) and Caucasian (C) |
| 429-W | Single and Multiple Dose Pharmacokinetics (PK) of Stavudine (d4T) from an Extended Release (XR) Formulation in Asymptomatic HIV-Infected Subjects Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 429-W Kaul S, Swaminathan A, Behr D, Nichola P, Gale J, O'Mara E; Bristol-Myers Squibb Pharmaceutical Res. Inst., Princeton, NJ BACKGROUND: A once daily (qd) formulation of d4T (XR) ( stavudine extended release capsules/prolonged release capsules) was developed to simplify HIV treatment. This study was designed to assess single- and multiple-dose PK and the safety and tolerability of d4T XR f |
| 430-W | Pharmacokinetics (PK) of Stavudine (d4T) Extended Release Formulation Compared with Stavudine Immediate Release (IR) Formulation as Part of Potent Antiretroviral Combination Therapy Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 430-W Kaul S, Damle B, Gale J, McKinely G, Slater L, Huang A, Brett-Smith H; Bristol-Myers Squibb Pharmaceutical Res. Inst., Princeton, NJ BACKGROUND: A once-daily (qd) formulation of d4T (XR) ( stavudine extended release capsules/prolonged release capsules) was developed to simplify HIV treatment. This study assessed the PK of a d4T XR formulation given qd compared to the currently available d4T (IR) c |
| 431-W | An Assessment of Plasma Amprenavir (APV) Pharmacokinetics (PK) Following Administration of Two GW433908 (908) and Ritonavir (RTV) Regimens in Combination with Efavirenz (EFV) in Healthy Adult Subjects (APV10010) Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 431-W M. B. Wire*1, C. Ballow2, S. Preston3, C. Hendrix4, Y. Lou1, P. Piliero3, and D. S. Stein1 Plasma APV concentrations were maintained when RTV 100-mg BID was co-administered with 908 700-mg BID + EFV 600-mg qd. The addition of an extra 100-mg of RTV (i.e. RTV 200-mg BID) did not provide significant additional enhancement of plasma APV concentrations. |
| 432-W | Comparative Pharmacokinetics and Short-Term Safety of Twice Daily (BID) Fortovase/Ritonavir and Invirase/Ritonavir Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 432-W Kurowski M, Sternfeld T, Hill A, Moecklinghoff C; HIV-LAB, Auguste-Viktoria Krankenhaus, Berlin, Germany Despite the poor bioavailability of Invirase as a sole protease inhibitor, pharmacokinetic enhancement with 100-mg of ritonavir produced plasma SQV concentrations that exceeded those of boosted Fortovase. Additionally, Invirase appears to be better tolerated than Fortovase. |
| 433-W | Multiple-Dose Kaletra (Lopinavir/Ritonavir) does not Affect the Pharmacokinetics of the CYP2D6 Probe, Desipramine Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 433-W R. Bertz*, C. Foit, Y-L. Chiu, B. Bernstein, S. Boller, J. R. Owen, L. Williams, Q. Ji, C. Renz, A. Hsu, G. R. Granneman, and E. Sun Consistent with predictions, LPV/r does not inhibit CYP2D6-mediated metabolism at clinically relevant concentrations. |
| 434-W | An Open-Label Steady State Investigation of the Pharmacokinetics (PK) of Tipranavir (TPV) and Ritonavir (RTV) and their Effects on Cytochrome P-450 (3A4) Activity in Normal Healthy Volunteers (BI 1182.5) Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 434-W S. McCallister*1, J. Sabo1, L. Galitz 2, and D. Mayers 1 TPV plasma concentrations were significantly enhanced in the presence of 100- or 200-mg of RTV to levels above the target IC50 for PI-resistant HIV-1. With each dose combination tested, TPV/RTV led to net inhibition of CYP3A4 activity. The vast majority of AEs were Grade I and involved the GI tract. |
| 435-W | Evidence of Systemic P-Glycoprotein (P-gp) Inhibitory Activity in Patients Receiving Twice-Daily Nelfinavir (Viracept). Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 435-W Donahue J, Dowdy D, Ratnam KK, Price J, McKinsey J, Unutmaz D, Nicotera J, Raffanti S, Becker M, Haas DW; Vanderbilt Univ. Sch. of Med., Nashville, TN BACKGROUND: Cellular P-gp effluxes HIV protease inhibitors (PIs) out of cells and some tissues (e.g., the brain). CD4+ and CD8+ T cells express P-gp. Although high PI concentrations inhibit P-gp activity in vitro, it is unclear whether this occurs in vivo. Nucleoside reverse transcriptase inhibitors (NRTIs) do not inhi |
| 436-W | Exploring Theoretical Mechanisms for Lack of Resistance to Lopinavir/Ritonavir (LPV/r) in Antiretroviral (ARV)-Naive Subjects. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 436-W A. Hsu, D. Kempf, G. R. Granneman, and E. Sun Theoretical simulations suggest that the lack of development of resistant virus in ARV-naïve subjects receiving LPV/r 400/100 mg BID might be attributed to its high plasma concentrations and relatively small changes in IC50 values between the initial mutants and wt viruses. The rapid decline in LPV plasma concentrations following missed doses, primarily due to declining ritonavir concentrations, may also contribute to the low incidence of LPV resistance in vivo |
| 437-W | Steady-State Indinavir (Crixivan) Pharmacokinetics in Cerebrospinal Fluid (CSF) and Plasma in Patients Receiving Low-Dose Ritonavir (Norvir), as Determined by Ultra-Intensive CSF Sampling. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 437-W D. W. Haas*1, B. Johnson1, J. Nicotera1, V. L. Bailey1, V. L. Harris1, F. Bowles1, S. Raffanti1,2, T. Finn3, J. Schranz3, A. Saah3, and J. Stone3 Low-dose RTV increased free IDV AUC in CSF 3-fold without affecting CSF:plasma AUC ratio (vs IDV 800 q8h without RTV. Free IDV level in CSF exceeded the IC95 of wild-type HIV-1 (100 nM) at all times in every patient. Low-dose RTV enhances IDV disposition into CSF primarily by increasing IDV plasma levels, but may also involve P-glycoprotein inhibition. |
| 438-W | Antiretroviral Distribution in Cerebrospinal Fluid and Viral Resistance in HIV-Infected Patients Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 438-W Antinori A, Perno CF, Giancola ML, Forbici F, Ippolito G, Hoetelmans R, Piscitelli S; Natl. Inst. of Infectious Diseases, L. Spallanzani, Roma, Italy BACKGROUND: The central nervous system is a potential reservoir of HIV. Differences exist in CSF drug penetration between antiretrovirals (ARVs), which may influence the development of resistant virus. CSF concentrations have been described for some ARVs but not for multiple drugs in a large patient population. METHODS |
| 439-W | Penetration of Lopinavir into the Genital Tract of HIV-1-Infected Men Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 439-W Sankatsing S, Burger D, Droste J, Jurriaans S, Lange J, Prins J; Academic Med. Ctr., Amsterdam, The Netherlands BACKGROUND: Penetration of antiretroviral drugs into anatomical sanctuary sites like the brain and the male genital tract is important, as suboptimal penetration might allow for ongoing viral replication despite systemic virological efficacy. Lopinavir (LPV) is a potent HIV-1 protease inhibitor, but so far there are no |
| 440-W | Pharmacokinetic Interaction between Lopinavir/r and Amprenavir in Salvage Therapy. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 440-W Solas C, Quinson AM, Couprie C, Ravaux I, Poizot-Martin I, Durand A, Lacarelle B; Timone Hosp., Marseille, France BACKGROUND: Lopinavir/r (LPV/r) plus amprenavir (APV) in multiexperienced patients is of growing interest that needs to be validated in terms of pharmacokinetic profile, safety, and efficacy. Ritonavir (RTV) present in LPV/r is a potent inhibitor of CYP3A4 and both |
| 441-W | Pharmacokinetics, Efficacy, and Safety of Once-Daily Saquinavir-sgc plus Low-Dose Ritonavir (1200/100 mg) in Combination with Efavirenz in HIV-Pretreated Patients. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 441-W Lopez-Cortes LF, Viciana P, Ruiz-Valderas R, Contreras R, Alarcon A; Hosp. Univ. Virgen del Rocio, Sevilla, Spain BACKGROUND: Sparing NRTI therapy can be a real option in case of severe adverse events or extensive NRTI resistance. PIs plus NNRTIs may be used, although their efficacy and safety have been no extensively assessed. The efficacy of SQV-sgc + RTV (1600/100 mg) once-daily is currently being evaluated with encouraging res |
| 442-W | Amprenavir is an Effective Inducer of Delavirdine Metabolism: A Steady-State Pharmacokinetic Interaction Study between Amprenavir and Delavirdine in Healthy Volunteers. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 442-W U. Justesen*1, N. Klitgaard2, K. Brosen1, and C. Pedersen2 There is clinically significant interaction between APV and DLV. A favourable increase in APV C12h but a dramatic decrease in DLV C12h is seen. The regimen, APV 600 mg BID and DLV 600 mg BID, is not recommended. Ongoing studies will elucidate whether other combinations are suitable for clinical use. |
| 443-W | Evaluation of Steady-State Interaction between Atazanavir (ATV) and Efavirenz (EFV) Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 443-W Preston S, Piliero P, O'Mara E, Mummaneni V, Randall D, Morvillo C, Geraldes M, Agarwala S, Drusano G; Albany Med. Coll., NY BACKGROUND: ATV is a new protease inhibitor (PI) with excellent anti-HIV activity. ATV may be combined with EFV (a non-nucleoside reverse transcriptase inhibitor) as part of a HAART regimen. EFV can induce cytochrome P450 (CYP) 3A and may lessen ATV exposure. The objective was to assess the pharmacokinetic (PK) profile |
| 444-W | Steady-State Pharmacokinetic Interaction Study of Atazanavir (ATV) with Efavirenz (EFV) and Ritonavir (RTV) in Healthy Subjects Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 444-W O'Mara E, Agarwala S, Randall D, Geraldes M, Stoltz R, Mummaneni V; Bristol-Myers Squibb Pharmaceutical Res. Inst., Princeton, NJ BACKGROUND: ATV is a new protease inhibitor (PI) with excellent anti-HIV activity and a cytochrome P450 (CYP) 3A substrate. EFV is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that induces cytochrome P450 (CYP) 3A. Addition of EFV to ATV (400-mg once-daily [qd]) reduced ATV exposure 74% vs ATV alone. RTV is |
| 445-W | Pharmacokinetic (PK) Effect of Rifabutin (RIF) on Atazanavir (ATV) with and without Ritonavir (RTV) in Healthy Subjects Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 445-W S. Agarwala*1, V. Mummaneni1, D. Randall1, M. Geraldes1, R. Stoltz2, and E. O'Mara1 ATV may be co-administered without modification at the standard dose of 400 mg with RIF. RIF dose modification may be necessary. |
| 446-W | Pravastatin 40-mg qd Does not Alter Protease Inhibitor (PI) Exposure or Virological Efficacy over 24 Weeks Therapy. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 446-W Moyle GJ, Buss NE, Gazzard B; Chelsea and Westminster Hosp., London, UK Introduction: Amongst cholesterol-lowering statins, pravastatin is thought to have the least impact on cytochromes P450. We have recently demonstrated that the efficacy of pravastatin plus dietary advice in persons receiving Pis is similar to endogenous hyperlipidaemia, reducing LDL cholesterol by 20%. METHODS: Patient |
| 447-W | Pharmacokinetics (PK) of Lower Doses of Saquinavir Soft Gel Caps (SQV) (800- and 1200-mg BID) with Itraconazole (Itra) Compared to 1400 mg SQV BID without Itra in HIV-1+ Thai Patients Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 447-W P. Cardiello*1,2, T. Samor1 , D. Burger3, R. Hoetelmans4, A. Mahanontharit1, K. Ruxrungtham1,5, J. Lange2 , D. A. Cooper6, and P. Phanuphak1 Lower doses of SQV (800 or 1200 mg BID) boosted with 100 mg Itra qd resulted in adequate PK parameters equivalent to SQV 1400 mg BID. Lower SQV doses boosted with Itra maintained therapeutic SQV levels, an important benefit in the developing world where drug access/affordability is a major obstacle in treating patients. |
| 448-W | Nelfinavir Unbound Drug Interactions and Protein Binding Characteristics. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 448-W F. Aweeka*1, T. Motoya2, L. Thevanayagam1, T. Blaschke3, J. Stone1, A. Jayewardene1, and J. Chi1 These in vitro results indicate that the protein binding of nelfinavir, a compound that binds extensively to both AAG and albumin, is not affected by concomitantly administered drugs exhibiting high protein binding. This is likely due to compensation of the alternate protein to bind up nelfinavir when the drug is displaced from AAG or albumin. These results suggest that free drug concentrations do not fluctuate due to drug interactions. |
| 449-W | Influence of Binding to Human Plasma Proteins by Protease Inhibitors may be Overestimated in Current IQ Models Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 449-W de Bethune MP, Xie D, Azijn H, Wigerinck P, Hoetelmans R, Pauwels R; Tibotec-Virco, Mechelen, Belgium BACKGROUND: Binding of antiretrovirals to plasma proteins is a factor that has been associated with lack of efficacy of some drug candidates. Most HIV- protease inhibitors (PIs) bind to a(1)-acid glycoprotein (AAG). The effect of this binding is quantified by measuring the activity of the inhibitors against wild-type H |
| 450-W | The Interim Analysis of a Phase IV Randomised, Open-Label, Multicentre Trial to Evaluate Safety and Efficacy of Indinavir/Ritonavir (800/100 mg BID) vs Saquinavir/Ritonavir (1000/100 mg MID) in Adult HIV-1 Infection: MaxCmin1 Trial. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 450-W A. Castagna*, U. B. Dragsted, J-P. Chave, A. Rieger, G. Carosi, S. van der Geest, H. Nielsen, and J. D. Lundgren for the MaxCmin1 Trial Group In the interim analysis at 24 weeks of this randomised trial no differences were observed in virological or immunological response to the 2 ritonavir-boosted study PIs nor in the proportion of patients with grade 3/4 AEs. No changes are warranted in the conduct of the trial following the Data and Safety Monitoring Board's evaluation of the week 24 data. Final results available in third quarter 2002. |
| 451-W | Pilot Study of Saquinavir-SGC (Fortovase, SQV) 1000 mg Twice Daily and Lopinavir/Ritonavir (Kaletra, LPV/r) in Protease Inhibitor-Experienced HIV+ Individuals: Dose Escalation and Combined Normalized Inhibitory Quotient (cNIQ) Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 451-W Hellinger J, Morris AB, Piscitelli S, Gordon D, Foy K, Jackson-Pope L, Cordeiro D, Peeters M, Hoetelmans R, de Caprariis PJ, Cohen C; Comm. Res. Initiative, Boston and Springfield, MA BACKGROUND: High levels of protease inhibitors (Pis) may be critical for treatment of HIV+ patients with multiclass drug resistance. METHODS: This is an open-label, single-arm, 48-week study of safety and antiviral activity of SQV + LPV/r in PI experienced, LPV-naïve subjects. NRTI choices guided by virtual phenotype ( |
| 452-W | Monitoring Intracellular Triphosphorylated Anabolites of Didanosine EC (ddI) and Stavudine (d4T): Results of a Pilot Clinical Study in HIV-Infected Patients Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 452-W Becher F, Landman R, Canestri A, Mboup S, Toure Kane C, Liegeois F, Vray M, Dalban C, Prevot MH, Leleu G, Benech H; CEA, Gif/Yvette, France BACKGROUND: A direct liquid chromatography tandem mass spectrometry (LC/MS/MS) assay was recently developed and validated to measure the active intracellular triphosphorylated anabolites of NRTIs in PBMC. The aim was to verify the relevance of this assay in samples coming from d4T-and ddI-treated patients and to approa |
| 453-W | Pharmacokinetics and Genotyping in Lopinavir Recipients with Prior PI Failure. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 453-W Boffito M, Arnaudo I, Bonora S, Sinicco A, Raiteri R, Hoggard P, Back D, Di Perri G; Univ. of Torino, UK BACKGROUND: Trough concentrations (Ctrough) of lopinavir (LPV) coadministered with ritonavir are reported to be 50- to 100-fold higher than the protein binding adjusted EC(50) for wild type HIV, but less favourable inhibitory quotients are seen when mutations in the protease genome have been |
| 454-W | Attainment of Higher Efavirenz Plasma Levels Allow to Regain Complete Virus Suppression in Patients Carrying NNRTI Resistance Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 454-W Gonzalez de Requena D, Gallego O, Briones C, Jimenez-Nacher I, Soriano V; Inst. de Salud Carlos III, Madrid, Spain BACKGROUND: NNRTIs exert a potent activity against HIV-1, although the development of single mutations at critical sites within the RT gene can reduce or even annul their activity. In this regard, the genetic barrier for efavirenz (EFV) seem to be greater than for |
| 455-W | Virological Failure Is Associated with Decreased 3TC Triphosphate (3TCTP) and Ratio of 3TCTP/Endogenous Deoxycytidine Triphosphate in HIV-Infected Individuals in a Clinical Setting Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 455-W Hoggard P, Kewn S, Lloyd J, Sales S, Wilkins E, Maher B, Meaden E, Almond L, Jones T, Pillay D, Sabin C, Khoo S, Back D; Univ. of Liverpool BACKGROUND: Cellular factors may be partly responsible for drug resistance to the dideoxynucleoside analogues, possibly due to decreased drug activation. Intracellular phosphorylation of these drugs to their triphosphates is essential for activity. The drug triphosphates (ddNTPs) then compete with endogenous deoxynucle |
| 456-W | Total Lymphocyte Count (TLC) as a Surrogate for CD4 Count to Initiate and Monitor HAART in Resource-Limited Countries. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 456-W Flanigan T, Mahajan A, Kumarasamy N, Mayer K, Carpenter C, Solomon S; Brown Univ. Med. Sch., Providence, RI BACKGROUND: Due to the prohibitively high cost of plasma viral load in resource-limited countries, monitoring of HIV progression and response to HAART largely depends on CD4 count. However, the routine use of CD4 count in management has also been hampered by high price per test. The cost of a single CD4 count in resour |
| 457-W | Review of Antiretroviral Therapy in the Private Sector in Nairobi, Kenya Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 457-W Macharia D, Lule G, Silverstein D, Tesfaledet G, Patel S, Owili DM, Chang LW, Nganga L, DeCock KM, Weidle PJ; CDC-Kenya, Nairobi BACKGROUND: Though the majority of the HIV-infected Africans who are aware of their HIV status and for whom antiretroviral (ARV) medications are clinically indicated cannot afford them, some can obtain drugs through the private sector. METHODS: We reviewed charts of patients who received ARVs from 5 private physicians |
| 458-W | Long-Term Evaluation (15 Months) of ddI, 3TC and Efavirenz Once-Daily Regimen in Naive Patients in Senegal: ANRS 12-04/IMEA 011 Study Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 458-W Landman R, Thiam S, Canestri A, Delaporte E, Mboup S, Vray M, Dalban C, Badiane S, Sow P, Niang AF, Gueye PM, Laniece I, Coulaud JP, Girard PM, Ndoye I; IMEA, Paris, France BACKGROUND: To assess the feasibility, efficacy and tolerance of once-a-day regimen combining didanosine (ddI), lamivudine ( 3TC ) and efavirenz (EFV) in adults infected with HIV1 in |
| 459-W | First Evaluation of d4T, ddI, and Efavirenz in Antiretroviral-Naive Patients in Senegal: ANRS 12-06 / IMEA 012 Study Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 459-W Landman R, Canestri A, Thiam S, Delaporte E, Mboup S, Vray M, Dalban C, Badiane S, Sow P, Niang AF, Gueye PM, Laniece I, Coulaud JP, Girard PM, Ndoye I; IMEA, Paris, France BACKGROUND: To assess the feasibility, efficacy and tolerance of the antiretroviral regimen combining stavudine ( d4T ) , didanosine EC (ddI) and |
| 460-W | The Senegalese Government HAART Initiative: An 18-Month Follow-Up Study of Feasibility, Effectiveness, Adherence, Toxicity and Viral Resistance Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 460-W Laurent C, Diakhate N, Fatou Ngom N, Sow P, Faye M, Gueye M, Laniece I, Toure Kane C, Liegeois F, Mboup S, Badiane S, Ndoye I, Delaporte E; IRD and Univ.of Montpellier, France BACKGROUND: Our objective was to study feasibility, effectiveness, adherence, toxicity, and viral resistance in an African government HAART initiative. METHODS: A prospective observational cohort study was started in Dakar in August 1998. Initial treatment consisted of 2 NRTIs and 1 PI. The primary endpoint for efficac |
| 461-W | Genotypic and Phenotypic Analyses of Drug Susceptibility in HIV-1 Isolates from Drug-Naive Patients in Nigeria Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 461-W Agwale SM, Zeh C, Paxinos E, Odama L, Pienazek D, Wambebe C, Kalish ML, Ziermann R; Natl. Inst. for Pharmaceutical Res. and Development, Abuja, Nigeria BACKGROUND: One of the major concerns in the AIDS pandemic is the extensive genetic variability of HIV-1. This affects the development of candidate vaccines and may impact antiretroviral therapy. METHODS: Env subtype was determined using a modified gp41-based heteroduplex mobility assay. A 1.2-KB fragment in the pol ge |
| 462-W | Survival of Persons with HIV Disease following Antiretroviral Therapy in Southern India Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 462-W Kumarasamy N, Mayer K, Flanigan T, Hemalatha R, Carpenter C, Thyagarajan SP, Solomon S; YRG Ctr. for AIDS Res. and Education, Chennai, India BACKGROUND: There are very few reports on the beneficial effects of antiretroviral therapy (ART) from developing countries. Here we report the survival time and adverse effects of persons who received antiretroviral therapy in a clinic-based population in Southern India . METHODS: This study was a r |
| 463-W | Safety, Tolerability, and Efficacy of Nevirapine-Based HAART amongst Antiretroviral Naive HIV-1-Infected Patients in India Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 463-W Pujari S, Naik E, Patel A, Bhagat S; Ruby Hall Clin., Pune, India BACKGROUND: Our objective was to determine safety, tolerability, and efficacy of nevirapine (NVP)-based HAART amongst antiretroviral naïve HIV-1-infected patients in tertiary care HIV clinics in Pune and Ahmedabad, India . METHODS: 347 antiretroviral-naïve subjects initiated on 2NRTIs+NVP were followed-up clinically mo |
| 464-W | Molecular Mechanism of DAPD Anti-HIV Activity against AZT and 3TC Mutants-Molecular Modeling Studies of HIV-1 RT. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 464-W Chong YH, Schinazi RF, Chu CK; Univ. of Georgia, Athens Bakground: DAPD/DXG is known to maintain the anti-HIV-1 activity against AZT and 3TC resistant mutants in vitro and in vivo. In order to understand the molecular mechanism of DAPD/DXG, molecular modeling studies of DXGTP complexed with the wild-type (WT) HIV-1 RT an |
| 465-M | The Impact of Baseline CD4 T-Cell Count and Adherence on Rates of Disease Progression among HIV-Infected Patients Initiating Triple Drug Therapy Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 465-M Wood E, Hogg R, Yip B, Craib K, O'Shaughnessy M, Montaner J; BC Ctr. for Excellence in HIV/AIDS, Vancouver, Canada BACKGROUND: We have reported increased risk of HIV disease progression if therapy is initiated when CD4 cell counts drop below 200 cells/mm(3), suggesting that 200 cells/mm(3) may approximate a biological threshold beyond which response to therapy is compromised. We now evaluate the roles of adherence and baseline CD4 |
| 466-M | Viral Dynamics and Their Relationships with Baseline Factors and Virologic Responses in Naive HIV-1-Infected Patients Receiving Abacavir in Combination with Selected HIV-1 Protease Inhibitors. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 466-M Wu H, Mellors J, McMahon D, Ruan P, Dix L, Spreen W, Kelleher D, Lederman M; Frontier Sci. and Technology Res. Fndn., Chestnut Hill, MA BACKGROUND: This was a study of HIV-1-infected patients receiving abacavir in combination with selected HIV-1 protease inhibitors . RESULTS: We found that the baseline HIV-1 RNA levels were highly predictive of the viral decay rates which are important markers for antiviral potency and |
| 467-M | Initiating Potent Combination Antiretroviral Therapy within 1 Year of the First Clinic Visit for Patients at All CD4 Cell Count Levels Is Associated with Better Long-Term Outcomes. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 467-M Kitahata M, Dillingham P, Van Rompaey S; Univ. of Washington, Seattle BACKGROUND: The optimal time to initiate antiretroviral treatment is unknown. Survival rates observed among patients who start therapy at high or low CD4 cell counts cannot be attributed solely to initiating treatment early or late in disease because of confounding with patients underlying disease stage, unless matched |
| 468-M | Impact of Initial CD4 Cell Response to Highly Active Antiretroviral Therapy (HAART) on Subsequent CD4 T-Cell Trends. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 468-M Shade SB, Hunt P, Martin JN, Deeks SG, Abrams DI; Univ. of California, San Francisco BACKGROUND: Following initiation of HAART, most patients experience rapid increases in CD4 cell count in the first few months of therapy. It is not known whether the magnitude of this initial rise is associated with subsequent CD4 cell response while viral load (VL) is undetectable, or whether it is associated with the |
| 469-M | When to Initiate Highly Active Antiretroviral Therapy (HAART): HIV Disease Progression According to CD4+ Level at Initiation of Therapy among Persons with Durable Virologic Suppression. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 469-M Sterling TR, Chaisson RE, Keruly J, Moore R; Johns Hopkins Univ., Baltimore, MD BACKGROUND: It is currently recommended that HAART should be initiated in asymptomatic persons when CD4 /= 90 days of a regimen including an HIV-1 protease inhibitor |
| 470-M | Impact of Baseline CD4 Cell Count and Viral Load on Durability of Virologic Response through 96 Weeks for Lopinavir/Ritonavir (LPV/r) and Nelfinavir (NFV) in a Phase III Clinical Trial Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 470-M M. King*, B. Bernstein, P. Cernohous, J. Moseley, E. Bauer, and E. Sun BACKGROUND: For a number of antiretroviral (ARV) agents, the time to virologic failure has been shown to be reduced among patients with baseline CD4 cell counts 100,000 copies/mL. In a phase II study of LPV/r in ARV-naïve patients, virologic response through 3 years was not decreased among patients with lower CD4 cell |
| 471-M | Viral Replication and Long-Term Clinical Progression in Patients Treated with Potent Antiretroviral Therapy. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 471-M M. Egger*1, B. Ledergerber2, P. Grob2, L. Perrin3, P. Burgisser4, P. Erb5, W. Fierz6, J-C. Piffaretti7, M. Gorgievski8, and R. Weber2 for the Swiss HIV Cohort Study (SHCS) Viral replication over time, as measured by the average viral load from AUC analysis, is a powerful predictor of clinical progression. Long-term suppression of viremia to undetectable levels must be the goal, once antiretroviral therapy is initiated. |
| 472-M | Greater Impact of HAART on Survival in People Age 50 and Older with HIV Infection Compared to Younger People in an Urban Observational Cohort. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 472-M Perez JL, Moore RD; Johns Hopkins Univ., Baltimore, MD BACKGROUND: HIV-infected people at least 50 years old progress to AIDS faster, have poor survival if untreated, and have a blunted CD4 cell recovery after starting HAART than younger individuals. If immune recovery is age-dependent, then HAART may have little clinical impact on older patients, who make up 10.8% of all |
| 473-M | Factors Associated with Immunologic Stage at which Patients Initiate Antiretroviral Therapy. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 473-M McNaghten A, Hanson DL, Kellerman S, Blair J, The Adult/Adolescent Spectrum of HIV Disease Project; CDC, Atlanta, GA BACKGROUND: Time of initiation of antiretroviral therapy (ART) has been an important issue due to its impact on morbidity and mortality. Current treatment guidelines recommend initiating ART at CD4 |
| 474-M | Frequency and Predictors of Late HIV Diagnosis in the United States, 1994 through 1999. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 474-M Neal JJ, Fleming PL; CDC, Atlanta, GA BACKGROUND: The first step of CDC s Serostatus Approach to Fighting the Epidemic (SAFE) is diagnosis of HIV infection in all infected individuals. Subsequent steps include linking HIV infected persons to care and prevention services, and supporting them in adhering to prescribed treatment and in adopting and sustaining |
| 475-M | Initial CD4+ T-Cell Counts in Patients with Newly Diagnosed HIV Infection Indicate that a Substantial Proportion of these Patients Have Advanced Disease Regardless of Gender, Race, or Socio-Economic Status. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 475-M Dybul M, Bolan R, Condoluci D, Cox-Iyamu R, Redfield R, Hallahan C, Sathasivam K, Folino M, Weisberg M, Andrews M, Hidalgo B, Vasquez J, Fauci AS; NIAID, NIH, Bethesda, MD BACKGROUND: CD4+ T-cell counts are a significant determinant of the stage of disease progression and prognosis in HIV-infected individuals. Thus, a diagnosis of HIV infection at a relatively high CD4+ T-cell count may be important for managing patients with regard to treatment decisions, which may ultimately impact pro |
| 476-M | Changes in both CD4 Cell Counts and HIV-1 RNA Levels Predict Subsequent Disease Progression among HIV-1-Infected Persons Initiating Antiretroviral Therapy Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 476-M Hogg R, Yip B, Chan K, Wood E, Harrigan PR, Craib K, O'Shaughnessy MV, Montaner JS; BC Ctr. for Excellence in HIV/AIDS, Vancouver, Canada BACKGROUND: Our objective was to describe the impact of changes in CD4 cell count and HIV-1 RNA levels on disease progression among HIV-1 infected persons initiating antiretroviral therapy. METHODS: A population-based analysis of antiretroviral therapy-naïve HIV-positive men and women 18 years or older in British Colum |
| 477-M | Recent Trends in Treatment Use and Virological Suppression in a London HIV Clinic Population Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 477-M Lampe F, Johnson MA, Loveday C, Chaloner C, Sabin C, Youle M, Kinloch S, Madge S, Phillips AN; Royal Free Centre for HIV Med., London, UK BACKGROUND: Introduction of HAART has transformed HIV treatment, but there is concern regarding the feasibility of its long-term use. We examined trends in treatment use and virological suppression among the HIV clinic population at the Royal Free Hospital, London, from 1999 to 2001, a period in which HAART has been th |
| 478-M | Short-Term Toxicity and Discontinuation of Antiretroviral Post-Exposure Prophylaxis Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 478-M Puro V, De Carli G, Mattioli F, Mariano Z, Ippolito G; INMI Spallanzani, Rome, Italy Although PI including PEP appears associated with a higher risk of side effects and discontinuation, these findings do not justify per se the exclusion of PI from the initial regimen. Indeed, our study showed that in most individuals the full-course, 3-drug regimen can be completed. Unless already contraindicated, we suggest beginning PEP with a 3-drug regimen and discontinuing the PI in the case of side effects that are not manageable, in order to prolong and possibly complete the 4 week treatment. |
| 479-M | Increased Initial Anti-HIV Activity and Decreased Initial CD4 T-Cell Response with Efavirenz (EFV) Added to Ritonavir (RTV) and Saquinavir (SQV) Treatment. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 479-M Cooper CL, Fraser C, Seguin I, Khaliq Y, Cote D, Hawley-Foss N, Badley AD, Garber GE, Gallicano K, Angel JB, Cameron DW; Ottawa Hosp. Res. Inst., Univ. of Ottawa, ON, Canada BACKGROUND: Possible differential virologic suppression and immunologic impact of antiretroviral drug classes warrant investigation into alternative antiretroviral combinations. METHODS: To assess early and long-term virologic and immunologic response to EFV-RTV-SQV therapy, antiretroviral-naïve adults with baseline pl |
| 480-M | Continued CD4+ T-Cell Count Gains in Patients with 4 Years of Suppressed Viral Load on HAART. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 480-M P. Hunt*1, S. G. Deeks1, B. Rodriguez2, H. Valdez2, S. B. Shade1, 3, D. Abrams1, 3, M. Krone1, T. Neilands1, M. Lederman2, and J. Martin1 In HAART-treated patients with sustained virologic suppression, CD4 counts continue to rise at 4 years after start of therapy. Intermittent low-level viremia does not affect the long-term CD4 response. The maximal capacity for CD4 restoration does not appear to be limited by low baseline CD4 counts. |
| 481-M | First Phase Immune Restoration Is Comparable in Antiretroviral (ARV) Naive Subjects Receiving a Protease Inhibitor (PI) or Triple-NRTI-Based ARV Regimen. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 481-M Landay A, Spritzler J, Kessler H, Mildvan D, Pu M, Fox L, Kuritzkes D, Lederman M, The 5014 Team; Rush Med. Coll., Chicago, IL BACKGROUND: Questions still remain as to whether the class (PI vs NRTI) of ARV might differentially affect the dynamics of cellular and functional immune restoration. METHODS: 55 ARV-naïve subjects were enrolled into an open-label trial and randomized to receive PI ( lopinavir / |
| 482-M | HAART Efficacy in Restoring HIV-Induced Abnormal B-Lymphocyte Function Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 482-M M. A. Jacobson*, H. Khayam-Bashi, D. Black, and V. Ng This study provides the longest reported observation to date of the effect of HAART on HIV-induced abnormal B-cell immune function. We observed that abnormal B-lymphocyte function (evidenced by elevation of IgG, paraproteins) persists despite >2 years of HAART-induced HIV suppression and CD4 count restoration. Larger, longer-term studies of HAART effect on B-cell reconstitution are needed to define the clinical sequelae of incomplete B-cell reconstitution and to suggest interventions that might lead to more complete immune reconstitution. |
| 483-M | Decreased Replication Capacity and R5(NSI) Phenotype, but not Host Factors, are Associated with a CD4/VL Discordant Response to PI-Based HAART Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 483-M Sufka S, Wrin T, Fiscus SA, Patel D, King H, Hellmann N, Hicks C; Duke Univ. Med. Ctr., Durham, NC BACKGROUND: A discordant response to highly active antiretroviral therapy (HAART) occurs when CD4 counts are stable or increased over time despite detectable viral load (VL). Proper clinical management of patients with this response requires improved understanding of the phenomenon. METHODS: 30 HIV+ patients (22 male, |
| 484-M | Increased T-Cell Turnover with HIV Infection Correlates Strongly with Immune Activation and does not Normalize after 52 Weeks of HAART Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 484-M Anthony K, Sereti I, Herpin B, Metcalf JA, Lane HC, Polis MA; NIAID, NIH, Bethesda, MD BACKGROUND: CD4 lymphopenia is the cardinal manifestation of HIV infection. The impact of increased turnover in CD4 loss and in HIV pathogenesis remains controversial. An evaluation of T-cell turnover before and after HAART was performed in order to study turnover changes induced by HAART as well as correlations of T-c |
| 485-M | Declines in CD4+ T-Cell Proliferation Rates Significantly Contribute to Increases in CD4+ T-Cell Telomere Length and TREC Levels in HIV-Infected Patients Undergoing HAART Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 485-M Prieto D, Kovacs J, Natarajan V, Douek D, Yoder C, Sidorov IA, Adelsberger JW, Metcalf JA, Stevens R, Koup R, Baseler MW, Dimitrov DS, Davey RT, Polis MA, Lempicki RA; SAIC, Frederick, MD BACKGROUND: HIV-1 infection is associated with increases in T cell proliferation and declines in telomere restriction fragment length (TRFL) and T cell receptor excision circles (TRECs), Treatment with HAART leads to increases in TRFL and TRECs. These results have been interpreted to suggest that the thymus plays a maj |
| 486-M | Individuals with Discordant Immunological Responses Following Combination Antiviral Therapy Have Elevated Levels of T-Cell Receptor Excision Circles Despite Increased Levels of T-Cell Proliferation. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 486-M Lewin S, Solomon A, Cameron PU, Crowe SM, Hoy J; Univ. of Melbourne BACKGROUND: Many HIV-1-infected patients treated with combination antiviral therapy develop rebounds in viral load (VL) in association with improvement in CD4+ T-cell counts. Recent evidence suggests that protease-inhibitor (PI)-resistant viruses replicate less efficiently in thymic tissue favoring sustained T-cell pro |
| 487-M | Discordant Responses during Antiretroviral Therapy: Role for Immune Activation and T-Cell Redistribution. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 487-M Hazenberg M, Otto S, van Baarle D, Kostense S, Wit F, Lange J, Hamann D, Miedema F; CLB/Sanquin and Landsteiner Lab. of the Academic Med. Ctr., Univ. of Amsterdam, The Netherlands BACKGROUND: Virus rebound during treatment with highly active anti-retroviral therapy (HAART) is usually associated with deterioration of the immune system, yet some patients maintain or improve CD4+ T-cell numbers despite virologic failure to HAART. We aimed to study the role of T cell activation in this process. METH |
| 488-M | The Effect of a Potent, 4-Drug Combination on Reducing HIV Unspliced mRNA and Proviral DNA in PBMC Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 488-M Mo H, Lu L, King M, Louie M, Markowitz M, Rooney J, Dusak B, Brun S, Richards B, Leonard J, Kempf D, Ho D, Sun E, Molla A; Abbott Labs., Abbott Park, IL BACKGROUND: The persistence of latently infected CD4+ cells represents a major barrier to virus eradication in patients on combination antiviral therapy. The half-life for decay of this latent pool of infected CD4+ T cells was estimated to be approximately 6 months in one study and 44 months in another. In this study, |
| 489-M | Immunologic Predictors of Discordance between CD4+ T-Cell and HIV-1 RNA Responses during Antiretroviral Therapy. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 489-M Spritzler J, Mildvan D, Russo A, Asthana D, Schock B, Livnat D, Kagan J, Landay A, Haas DW; Harvard Sch. Publ. Hlth., Boston, MA BACKGROUND: We wanted to determine whether immunologic markers predict later discordance between CD4+ T-cell and HIV-1 RNA changes during antiretroviral therapy. METHODS: This analysis included 10 prior antiretroviral studies, and 1,126 evaluable treatment-naïve and -experienced subjects. 4 intervals were studied: from |
| 490-M | Immunological and Virological Characteristics of HIV-Infected Patients with Discordant Response to Highly Active Antiretroviral Therapy Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 490-M Vella S, D'Ettorre G, Palmisano L, Nicastri E, Parisi SG, Andreotti M, Sarmati L, Galluzzo CM, Mastroianni C, Vullo V, Concia E, Andreoni M; Inst. Superiore di Sanita, Rome BACKGROUND: Discordant response to HAART is reported in 20-40% of HIV+ subjects. So far, pathogenic mechanisms involved have not been fully clarified, and there is no agreement about therapeutic management of these subjects. METHODS: 2 groups of patients were studied: A) 20 with immunological response (>100 CD4+ cells/ |
| 491-M | Rapid Initial Decay of Latently Infected Cells Following the Re-Initiation of HAART in Chronically HIV-1-Infected Patients with Treatment Interruptions Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 491-M Blankson J, Siliciano J, Finzi D, Quinn T, Gallant J, Siliciano R; Johns Hopkins Univ. Sch. of Med., Baltimore, MD BACKGROUND: Structured treatment interruptions have been proposed as a strategy to minimize the cost and toxicity of long-term HAART while also providing a mechanism to enhance HIV-1-specific immunity. Prior studies have reported a rapid rebound in viremia and a significant increase in the latent reservoir in resting C |
| 492-M | Intrinsic Decay Rate of Lymphocyte Reservoirs of HIV-1 Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 492-M Strain MC, Havlir D, Gunthard H, Ignacio C, Macaranas T, Daly OA, Fischer M, Opravil M, Leigh-Brown AJ, Levine H, Kwok S, Christopherson C, Smith D, Spina C, Richman DD, Wong JK; Univ. of California, San Diego BACKGROUND: Long-lived, cellular reservoirs of HIV are an obstacle to eradication of infection despite highly active antiviral therapy (HAART). Assessment of clearance rates of cellular reservoirs is complicated by possible replenishment by residual replication. METHODS: 9 chronically HIV patients who had received 0.5- |
| 493-M | Levels of Cell-Free HIV Virions Released by Latently Infected, Resting CD4+ T Cells: Implications for Ongoing Viral Replication. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 493-M Chun TW, Justement J, Pandya P, Liu S, McLaughlin M, Ehler L, Fauci AS; NIAID, NIH, Bethesda, MD BACKGROUND: The persistence of HIV in latently infected, resting CD4+ T cells has been demonstrated in infected individuals. It has been suggested that this viral reservoir does not produce HIV without cellular stimulation. However, it has been demonstrated that CD4+ T cells lacking activation markers continue to expre |
| 494-M | Peripheral Blood Dendritic Cells are not a Major Reservoir for HIV-1-Infected Individuals on Virally Suppressive HAART Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 494-M Otero M, Nunnari G, Dornadula G, Patel C, Frank I, Pomerantz RJ Thomas Jefferson Univ., Philadelphia BACKGROUND: Dendritic cells (DCs) are potent antigen-presenting cells, and their physiological localization in tissues which interact with the external environment is important as an initial barrier against pathogens such as human immunodeficiency virus type I (HIV-1). Therefore, DCs are a key step in infection of indi |
| 495-M | Viral- and HIV-Specific CTL Dynamics during Intermittent Antiretroviral Therapy in Chronically HIV-Infected Patients. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 495-M Oxenius A, McLean A, Fischer M, Hafner R, Schneider C, Joller H, Price D, Dawson S, Hirschel B, Phillips R, Weber R, Gunthard H, The Swiss HIV Cohort Study; Oxford Univ., UK BACKGROUND: We wanted to evaluate whether repeated structured treatment interruptions can lower viral setpoints and whether such changes can be predicted by viral- and HIV-specific CTL dynamics. METHODS: 13 chronically HIV-infected patients enrolled in the Swiss Spanish Intermittent Therapy Trial, participated in a sub |
| 496-M | Autologous Neutralizing Antibody (ANAB) to Concurrent and CD4 T-Cell-Recovered Virus in HIV Infected Children on HAART. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 496-M Ching N, Wei L, Deville J, Nielsen K, Wolinsky S, Bryson Y; Univ. of California, Los Angeles BACKGROUND: A patient s ability to produce NAB to current and past HIV isolates may be correlated with reduced disease progression and protection against maternal fetal transmission. Little is known about the effect of prolonged viral suppression by HAART on the NAB response in HIV infected infants and children. We ass |
| 497-M | Mucosal Cytokines/Chemokines are Increased by as much as 75-fold in HAART-Treated Subjects with Detectable Plasma Viral Loads Compared to Those with Fully Suppressed Viremia Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 497-M Elliott J, Boscardin WJ, Poles M, McGowan I, Fuerst M, Taing P, Anton P; Univ. of California AIDS Inst., Los Angeles BACKGROUND: The normal gut mucosa expresses levels of chemokines/cytokines that maintain low-level inflammation. Increased expression of pro-inflammatory cytokine mRNA is seen in the mucosa of untreated HIV-infected patients. These cytokines up-regulate HIV replication, contribute to apoptosis, and recruit additional t |
| 498-M | Differential Gene Expression in Chronically Infected HIV Patients Initiating HAART and Long-Term HAART Recipients Interrupting Therapy Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 498-M Dennis G, Yang J, Bosche M, Hosack D, Sherman B, Sidorov IA, Dimitrov DS, Adelsberger JW, Metcalf JA, Stevens R, Baseler MW, Davey RT, Polis MA, Lane HC, Lempicki RA; SAIC, Frederick, MD BACKGROUND: HIV-1 infection is associated with a decline in CD4+ T-cell numbers and systemic immune activation that leads to a generalized immunosuppressive state. The advent of HAART has significantly improved immune function despite being linked to metabolic side effects. To more fully understand the molecular mechan |
| 499-M | Immune Correlates of a Discordant CD4/VL Response to PI-Based HAART Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 499-M Sufka S, Ferrari G, Sempowski G, Staats H, Gryszowka V, Teaberry V, Weinhold K, Hicks C; Duke Univ. Med Ctr., Durham, NC BACKGROUND: A discordant response to highly active antiretroviral therapy (HAART) occurs when CD4 T-cell counts are stable or increased over time despite detectable viral load (VL). The role of humoral and cellular immune responses in this phenomenon are still undetermined. METHODS: 30 HIV+ patients (22 male, 8 female; |
| 500-M | Human Cytomegalovirus (HCMV)-Specific CD4+ and CD8+ T-Cell-Mediated Immunity in AIDS Patients following HAART Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 500-M G. Piccinini*1, D. Lilleri1, G. Comolli1, E. Genini1, L. Minoli1, A. D’Arminio2, M. Catalina3, L. Gibson3, K. Luzuriaga3, M. G. Revello1, and G. Gerna1 After 43 months of HAART a fair proportion of AIDS patients with pre-HAART CD4+ T cells <50/mL did not reconstitute the CD4-specific immune response, and in group B 30% of patients lost immune response after 10 months follow-up; CFC and LPR agreed in about 80% of samples in detecting HCMV T-helper response; in the great majority of patients with no CD4+ immune response, HCMV-specific CD8+ were detected in the absence of HCMV disease, thus suggesting that CD8+ might protect against HCMV disease. |
| 501-M | Disease Stage Does Not Influence the Frequencies of HIV-1-Specific Th1 Cells after Long-Term of Highly Efficient Antiretroviral Therapy Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 501-M Carcelain G, Alatrakchi N, Samri A, Tubiana R, Duvivier C, Hilpert S, Perrin V, Debre P, Katlama C, Autran B; Hosp. Pitie-Salpetriere, Paris, France BACKGROUND: The aim of the study was to evaluate HIV-1-specific Th1-cell frequencies in large groups of patients treated for 1 to 3 years at different stages of the disease. METHODS: 79 HIV-1-infected patients (63 treated in chronic infection and 16 in primary infection [PI]) were enrolled in a study of CD4+ T-cell res |
| 502-M | Immune Reconstitution in HIV-Infected Children following Antiretroviral Therapy Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 502-M Haridas V, Chandrasekaran A, Chavan S, Pahwa S; North Shore-Long Island Jewish Res. Inst. Immunology Ctr., Manhasset, NY BACKGROUND: Immune reconstitution following antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected patients may result from recovery of thymic function, peripheral redistribution, or decreased T-cell destruction. In the present study we have investigated thymic function by estimating the levels of |
| 503-M | Functional Restoration of Human Immunodeficiency Virus and Epstein-Barr Virus-Specific CD8+ T Cells during HAART Is Associated with an Increase in CD4+ T Cells. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 503-M van Baarle D, Kostense S, Otto S, Nanlohy NM, Jansen C, Lange J, van Oers MH, Miedema F; Academic Med. Ctr., The Netherlands BACKGROUND: To investigate the effect of highly active antiretroviral therapy (HAART) on HIV- and EBV-specific CD8+ T cells, total number and function of these cells was determined using tetrameric HLA-peptide complexes and IFN-g ELISPOT assays after peptide-stimulation, respectively. METHODS: 16 HIV-infected individua |
| 504-M | Impaired Responses to Immunization in HIV-Infection despite CD4+ T-Cell Restoration after Suppressive Antiretroviral Therapy. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 504-M Lange C, Valdez H, Medvik K, Asaad R, Wild M, Kalayjian R, Lederman M; Univ. Hosp., Cleveland, OH BACKGROUND: Responses to immunization are indices of general immune competence requiring integrity of both afferent and efferent limbs of the immune system. This study was designed to examine the responses to immunization with recall and neo-antigens in persons with normal CD4+ T-cell counts after successful antiretrov |
| 505-M | Persistence of Infectious HIV in both Memory and Naive CD4 T-Cell Subsets in Patients on Prolonged and Effective HAART Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 505-M Lambotte O, Demoustier A, de Goer MG, Wallon C, Gasnault J, Goujard C, Delfraissy JF, Taoufik Y; INSERM E-0109 BACKGROUND: Patients on prolonged and effective HAART have been demonstrated the persistence of infected CD4+ T cells that harbor latent replication-competent virus. To investigate the phenotypic features of these infected lymphocytes, we examined 4 highly purified subsets of memory and naïve CD4+ T cells for the prese |
| 506-M | Reevaluation of T-Cell Receptor Excision Circles as a Measure of Human Recent Thymic Emigrants Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 506-M Ye P, Kirschner D; Univ. of Michigan, Ann Arbor BACKGROUND: The human thymus exports newly generated T cells to the periphery. As no markers have been identified for these recent thymic emigrants (RTE), it is currently impossible to measure human thymic output. The T-cell receptor excision circle (TREC) assay has been recently developed to assess thymic output durin |
| 507-M | Dynamics of Lymphocyte Activation, Proliferation, and Death in HIV-1 Infection. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 507-M Ribeiro RM, Mohri H, Ho D, Perelson AS; Los Alamos Natl. Lab., NM BACKGROUND: A consequence of HIV-1 infection is the loss of CD4+ T cells. Several hypotheses have been proposed to explain T-cell depletion, including decreased production of T cells, increased death, or both. We used deuterated glucose labeling of T cells and modeling to show that T-cell production is not impaired and |
| 508-M | HIV Infection Induces a Quantitative and Qualitative Impairment of Thymic Function that Is Partially Restored under HAART Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 508-M Poulin JF, Bordi R, Sylvestre M, Routy JP, Woods R, Montaner J, Sekaly RP, Cheynier R; Ctr. de Recherche du CHUM, Montreal, QC, Canada BACKGROUND: Evaluation of thymic function contribution to the peripheral T-cell homeostasis is a matter of great importance. Recently, a new approach to monitor thymic activity has been validated. This concept aims at detecting within peripheral blood mononuclear cells (PBMCs) by-products of T-cell receptor (TCR) alpha |
| 509-M | Positive Feedback on CXCR4-Tropic HIV Infection in the Thymus is Regulated through Interleukin (IL)-7. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 509-M Okamoto Y, Douek D, Koup R; NIAID Vaccine Res. Ctr., NIH, Bethesda, MD BACKGROUND: We have previously shown that exogenous IL-7 can prevent apoptosis and enhance proliferation of immature thymocytes, and also increase CXCR4- (X4) or CCR5- (R5) HIV production in thymic organ culture (TOC). Recent data indicate that plasma IL-7 levels are strongly correlated with T-lymphopenia and viral loa |
| 510-M | Alteration of the IL-7 Homeostatic Response to T-Cell Depletion during the Course of HIV Infection. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 510-M Routy JP, Smith G, Boulassel R, Gilmore N, Klein M, MacLeod J, LeBlanc R, Sekaly RP, Cheynier R, Lalonde R; McGill Univ, QC, Canada BACKGROUND: Interleukin-7 (IL-7) is a potent stimulator of thymic and extra-thymic lymphopoiesis and enhances HIV replication in vitro. Several reports have shown a strong inverse correlation between IL-7 plasma levels and T-cell lymphopenia in advanced HIV-infected patients (CD4 |
| 511-M | Increased Thymic Mass and Circulating Naive CD4+ T-Cell Counts in HIV-1-Infected Adults Treated with Growth Hormone. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 511-M Napolitano L, Lo J, Gotway M, Mulligan K, Barbour JD, Schmidt D, Halvorsen R, Stoddart C, Schambelan M, McCune JM; Gladstone Inst. of Virology and Immunology, San Francisco, CA BACKGROUND: Growth hormone (GH) plays an integral role in the development and maintenance of the immune system in animals, raising the possibility that its administration may be of therapeutic benefit in human immunodeficiency. We hypothesized that GH might augment thymopoiesis in individuals infected with the human im |
| 512-M | Limited Thymic Contribution to Initial CD4 T-Cell Restoration during Supplementation of HAART with IL-2 and/or Remune. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 512-M Pido-Lopez J, Burton C, Hardy G, Pires A, Aspinall R, Gazzard B, Gotch F, Imami N; Imperial Coll. of Sci., Technology and Med., London, UK BACKGROUND: Our objective was to determine the effect of treatment with HAART alone or in conjunction with interleukin-2 ( IL-2 ) and/or immunization with inactivated gp120-depleted immunogen (Remune) on the thymic function of HIV-1-infected individuals. METHODS: The T-cell receptor excision circles (TRECs) assay was u |
| 513-M | Growth Hormone Enhances Thymocyte Development and Induces Differentiation into Functional Peripheral T Cells in HAART Treated HIV-1+ Patients. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 513-M Pires A, Pido-Lopez J, Moyle G, Gazzard B, Gotch F, Imami N; Imperial Coll. of Sci., Technology, and Med., London, UK BACKGROUND: Administration of human recombinant growth hormone (hrGH) with HAART in HIV-1 infection may increase thymic activity, resulting in the production of naïve T cells, and drive differentiation into functional peripheral memory/effector cells. METHODS: 12 chronic HIV-1-infected individuals (mean age 43.4 ± 7 |
| 514-M | Long-Term Efficacy of Subcutaneous IL-2 Therapy in HIV Infection. Final Analysis of the ANRS 079 Randomized Trial and Long-Term Follow-up Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 514-M Levy LY, Durier C, Lascaux AS, Capitant C, Michon C, Weiss L, Oksenhendler E, Gastaut JA, Goujard C, Rouzioux C, Aboulker JP, Delfraissy JF The ANRS 079 Study Group; Hosp. Henri Mondor, Creteil BACKGROUND: Our goal was to assess the long term efficacy of SC IL-2 . METHODS: 118 patients naïve to antiretrovirals or naïve to PI were randomized to start and receive over 74 weeks D4t+ 3TC + indinavir either alo |
| 515-M | Long-Term Efficacy of Subcutaneous IL-2 Therapy in HIV Infection: Pro-Viral DNA in Patients of the ANRS 079 Trial Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 515-M Burgard M, Durier C, Capitant C, Lascaux AS, Michon C, Netzer E, Goujard C, Foubert V, Aboulker JP, Delfraissy JF, Levy Y, Rouzioux C, The ANRS 079 Study Group; Paris, France BACKGROUND: Our objective was to assess the long-term effect of IL-2 therapy on the stock of latently HIV-infected cells, by quantifying proviral DNA in PBMC. METHODS: ANRS 079 is a randomized study of HAART +/- sc IL2 therapy in naïve (n=66) or pretreated patients (n=50). All patients who had frozen aliquots of PBMC w |
| 516-M | Efficacy of Intermittent Subcutaneous Interleukin-2 (IL-2) in Antiviral-Experienced HIV-Infected Individuals with Detectable Viral Load: 3-Year Extended Follow-Up. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 516-M Nozza S, Magenta L, Poli G, Rizzardi GP, Lazzarin A, Tambussi G; Clin. of Infectious Diseases, San Raffaele BACKGROUND: At the end of the main study, all individuals were evaluated as outpatients with determination of their peripheral CD4+ T-cell counts on a monthly basis, and of their viremia levels every 3 months. METHODS: Patients underwent new cycles of IL-2 (3 MIU/BID for 5 days every 4 weeks) if the number of circulati |
| 517-M | Baseline Characteristics Associated with CD4+ Response after 3 Cycles of Subcutaneous (SC) Recombinant Human Interleukin-2 (IL-2). Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 517-M Labriola A, Denning E, Klimas N, Gordin F, U.S. Dept. of Veterans Affairs Natl. Trial Coordinating Ctr, The ESPRIT Study Group; VA Med. Ctr. Washington, DC BACKGROUND: ESPRIT is an open-label, randomized, controlled trial to determine if (SC) IL-2 therapy + combination antiretroviral therapy (ART) vs ART alone reduces risk of AIDS or death in patients with baseline CD4 ≥300 c/micro-L. IL-2 was given BID in 3 5-day cycles q8 weeks, with more cycles if CD4 did not |
| 518-M | Preliminary Analysis of the Safety and Immunologic Activity of Recombinant IL-2 in Children and Adolescents with HIV Infection Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 518-M Wood LV, Zuckerman J, Steinberg S, Liewehr D, DeCarlo E, Beals M, Wigginton J, The Pediatric HIV Working Group; NCI, NIH, Bethesda, MD BACKGROUND: Quantitative and qualitative defects in immune function often persist despite treatment with highly active antiretroviral therapy (HAART). Interleukin-2 ( IL-2 ) is a critical mediator of both cellular and humoral immune function and may contribute to the reconstitution and preservation of immune function i |
| 519-M | Effect of Interleukine-2 (IL-2) on Hepatitis C Virus (HCV) in HIV-1/HCV Co-Infected Patients Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 519-M Lopez JC, Cosin J, Catalan P, Berenguer J, Miralles P, Padilla B, Rivera M; Hosp. Gregorio Maranon, Madrid, Spain BACKGROUND: Treatment with IL-2 in HIV-1 infected patients leads to an increase in the CD4 cell counts. In our media, co-infection with HCV is very common in HIV-1 infected patients. However there are not data regarding the effects of IL-2 on HCV, as well as a possible increasing of hepatic toxicity in this situation. |
| 520-M | Emergence and Selection of Viral Immune Escape Following Antiretroviral Therapy and IL-2 Suspension in Primary and Chronic SIVmac251 Infection of Rhesus Macaques Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 520-M Nacsa J, Stanton J, Hel Z, Kunstman K, Tryniszewska E, Tsai WP, Giuliani L, Altman J, Watkins DI, Lewis MG, Markham P, Nixon DF, Tartaglia J, Smith KA, Wolinsky S, Franchini G; NCI, NIH, Bethesda, MD BACKGROUND: IL-2 , as an adjunct to antiretroviral therapy, increases the absolute number of CD4+ T cells in HIV-1-infected individuals. However, the long-term clinical benefit of IL-2 treatment is unknown. In macaques infected with SIVmac251, it is however possible to ascertain the clinical, virological, and immunolog |
| 521-M | Phase I Study of Anti-LFA-1 Monoclonal Antibody (Cytolin) in Adults with HIV Infection. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 521-M Northfelt D, Allen A, Kapustay P; Univ. of California, San Diego BACKGROUND: Human lymphocyte function-associated antigen (LFA)-1 is a heterodimeric lymphocyte surface glycoprotein. LFA-1 is expressed on CD8+ cytotoxic T lymphocytes (CTLs) prevalent in HIV-infected individuals and may be involved in the progressive depletion of CD4+ T-cell counts. Anti-LFA-1 monoclonal antibodies (m |
| 522-M | Non-Specific Immunotherapy with Murabutide Significantly Improves Responses to Recall and to HIV-1 Antigens, in Patients Naive to Antiretroviral Therapy. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 522-M De La Tribonniere X, Yazdanpanah Y, Mouton Y, Bahr GM; Infectious Diseases, Tourcoing BACKGROUND: The synthetic immunomodulator Murabutide (MB) has been reported to enhance non-specific immune defense mechanisms, to regulate cytokine synthesis, and to control HIV-1 replication in antigen-presenting cells. Method: Following successful phase I studies in HIV-1 patients, we carried out a comparative trial |
| 523-M | The Effects of GM-CSF on Plasma HIV-1 RNA and CD4 Lymphocyte Counts in HIV-1-Infected Subjects Receiving Concomitant Potent Antiretroviral Therapy. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 523-M Jacobson J, Lederman M, Spritzler J, Valdez H, Tebas P, Skowron G, Wang R, Jackson JB, Fox L, Gilbert M, The ACTG 5041 Team; Mount Sinai Sch. of Med., New York, NY BACKGROUND: Earlier studies reported improvements in plasma HIV RNA levels and CD4 lymphocyte counts in patients with HIV infection after treatment with GM-CSF. METHODS: In ACTG 5041, 116 patients were enrolled in a randomized, double-blind, placebo-controlled evaluation of 16 weeks of GM-CSF (250 micro-g sc 3 times pe |
| 524-M | Phenotypic and Functional Characterization of Dendritic Cells Generated from Monocytes of HIV-Infected Patients in the Presence of GM-CSF and Interferon-alpha. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 524-M Carbonneil C, Weiss Laurence L; INSERM U430 Hosp. Broussais, Paris, France BACKGROUND: We previously demonstrated that DC differentiated from monocytes of HIV-seronegative individuals, in the presence of GM-CSF and IFN-alpha (GM/IFN DC) produced IL-12 and were capable of inducing CD8 response to HIV lipopeptides thus exhibiting functional characteristics of type 1 DC. METHODS: In the present |
| 525-M | Long-Term Persistence and Safety of Gene-Modified Syngeneic CD4+ T Lymphocytes in HIV-Infected Patients. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 525-M Lu A, Tavel J, Herpin B, Natarajan V, Davey RT, Kovacs J, Falloon J, Polis MA, Masur H, Lane HC; NIAID, NIH, Bethesda, MD BACKGROUND: Since HIV infection can be considered an acquired genetic disease, gene therapy has been proposed as a potential addition to current antiretroviral regimens in the treatment of HIV-infected patients. However, data regarding the long-term safety and in vivo cell persistence of genetically modified cells in H |
| 526-M | Activation of an HIV-1 Reservoir during Hematopoietic Progenitor Cell Mobilization Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. Rapaport R, Kuritzkes D, Schooley RT, Campbell TB; Univ. of Colorado Hlth. Sci. Ctr., Denver BACKGROUND: Although latently infected resting CD4+ T cells serve as a reservoir for HIV-1, other undefined viral reservoirs may also exist and contribute to viral persistence. This study investigated the possibility that increased viral replication during G-CSF-mediated hematopoietic stem cell (HSC) mobilization resul |
| 527-M | Interleukin-2 (IL-2) Added to HAART in Primary HIV Infection Enhances Anti-HIV Immune Responses Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 527-M Hecht F, Kahn J, Martinez-Marino B, Altfeld M, Liu L, McGrath, Gascon R, Busch M, Walker B, Levy J; Univ. of California, San Francisco BACKGROUND: The aim of this study is to determine whether adding IL-2 to HAART in treatment of primary HIV improves immune responses to HIV and virologic and clinical outcomes. IL-2 may directly enhance anti-HIV cellular immune responses, and through increasing expression of HIV antigens it may elicit immune responses |
| 527a-M | Increases in Naive CD4+ T Cells in IL-2-Treated HIV Patients is Primarily Due to Peripheral Expansion of Existing Naive CD4+ T Cells. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 527a-M Natarajan V, Lempicki RA, Sereti I, Badralmma Y, Adelsberger JW, Metcalf JA, Stevens R, Baseler MW, Kovacs JA, Lane HC; SAIC, Frederick, MD BACKGROUND: Intermittent IL-2 therapy in patients with HIV infection has been shown to preferentially increase the number of CD4+ T cells with a naïve phenotype. The underlying mechanism by which IL-2 treatment increases CD4+ cells is not fully understood. The increase could be due to the proliferation of existing cell |
| 528-M | SSITT: A Prospective Trial of Treatment Interruptions in HIV Infection. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 528-M Hirschel B, Fagard C, Oxenius A, Gunthard H, Garcia F, The Swiss HIV Cohort Study; Geneva, Switzerland BACKGROUND: Re-exposure to HIV during planned treatment interruptions may stimulate anti-HIV immunity (the autovaccination hypothesis). METHODS: Patients recruited for SSITT had been on HAART, with viral suppression to |
| 529-M | Structured Treatment Interruptions (STI) in Patients Receiving HAART since Primary HIV-1 Infection (PHI): Spontaneous Control of Viremia in about One Third of Cases after the First 3 Cycles Off Therapy Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 529-M Miro J, Plana M, Ortiz GM, Maleno MJ, Arnedo M, del Rio A, Claramonte X, Garcia A, Lazzari E, Joseph J, Pumarola T, Nixon DF, Gallart T, Gatell JM; Univ. of Barcelona, Spain BACKGROUND: The goal was to determine whether 4 cycles of STI can restore HIV-1-specific T-cell responses (CD4+ and CTL) and control HIV-1 replication in patients who started HAART within 90 days after onset of PHI symptoms. METHODS: 12 consecutive patients with sustained viral suppression ( 1 after |
| 530-M | Structured Treatment Interruptions (STI) in Acute Seroconverters: Interim Results of the Multicenter Prospective PRIMSTOP Pilot Trial (ANRS 100). Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 530-M Hoen B, Burgard M, Fournier I, Lacabaratz C, Raffi F, Lafaurie M, Livrozet JM, Rouzioux C, Venet A, Aboulker JP, The Primstop Study Team; Univ. Hosp., Besancon BACKGROUND: HIV cannot be eradicated even when HAART is started early in the course of primary infection. The main objective of this trial was to evaluate the capacity of a treatment regimen consisting of a 34-week HAART induction phase followed by a 50-week STI phase to induce specific anti-HIV immune response and eff |
| 531-M | Long-Term Multicompartment Evolutionary Study of HIV-env in a Chronically HIV-Infected Patient before and during HAART Followed by 5 Structured Treatment Interruptions (STI). Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 531-M Joos B, Fischer M, Trkola A, Boni J, Kuster H, Oxenius A, Wong JK, Phillips R, Hirschel B, Weber R, Gunthard H; Univ. Hosp., Zurich and Geneva BACKGROUND: Extensive study on HIV env sequence evolution over 5 years in a patient undergoing multiple STI cycles and induction of host immune responses. METHODS: Patient history: Infected with HIV-1B without therapy for > 6 years. Successful ART for 34 months. Enrollment into Swiss Spanish Intermittent Therapy Trial |
| 532-M | Drug-Resistant HIV-1 Variants Selected in Children with Intermittent Low-Level Plasma HIV-1 RNA (Blips) during HAART. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 532-M Tobin NH, Wang Y, Melvin AJ, DeVange S, McKernan J, Ellis GM, Mohan KM, Pepper G, Heath L, Naugler WE, Beck IA, Lewis P, Learn GH, Mullins J, Frenkel LM; Univ. Washington, Seattle BACKGROUND: The significance of intermittent low-level viremia (50-500 copies/mL) in HIV-infected patients on therapy is unknown. Published data suggest the transcription of archival virus only, however, our studies demonstrate the selection of drug-resistant HIV-1 variants during effective HAART. METHODS: To evaluate |
| 533-M | Maintenance Therapy with HU-ddI after Complete Viral Suppression on HAART: Results at 48 Weeks. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 533-M Barreiro P, Camino N, de Mendoza C, Soriano V, Blanco F, Valencia E, Gonzalez-Lahoz J; Hosp. Carlos III, Madrid, Spain BACKGROUND: HAART improves life expectancy of HIV+ patients, although adherence and toxicity are major concerns. HU-ddI is a simple regimen (3 pills daily), which combines a cytostatic effect (HU limits HIV target cell availability) and antiviral potency (HU enhances ddI activity). METHODS: All subjects with VL |
| 534-M | Effect of Associating an Immunosuppressive Therapy (Mycophenolate Mofetil: MMF)+HAART during STI and Holding the MMF Drug after Definitive Interruption of HAART on Viral Replication. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 534-M Garcia F, Plana M, Brunet M, Arnedo M, Alcami J, Lopez-Galindez C, Tenner-Racz K, Gil C, Vidal E, Mestre G, Martorell J, Cruceta A, Miro J, Pumarola T, Gallart T, Racz P, Gatell JM; Univ. of Barcelona, Spain BACKGROUND: To study the effect of associating MMF+HAART and holding MMF after cycles of STI on plasma and tonsillar tissue viral replication (TTVL). The PK of MMF and the effect on lymphocyte subsets and proliferative responses (LPR) were also assessed. METHODS: 15 CHI patients in very early stage (BVL 200-5000 copies |
| 535-M | Effect of Associating a Cytostatic Drug+HAART and Holding the Cytostatic Drug after STI and a Definitive Interruption of HAART on HIV-1-Specific Immune Responses. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 535-M Plana M, Lopalco L, Garcia F, Ortiz GM, Maleno MJ, Garcia A, Arostegui J, Miro J, Nixon DF, Gil C, Cruceta A, Arnedo M, Pumarola T, Alcami J, Lori F, Gallart T, Gatell JM; Univ. of Barcelona, Spain BACKGROUND: Our goal was to study the effect of hydroxyurea (HU) vs HU plus ART on HIV-1-specific neutralizing antibodies activity (NA), CTL, and helper responses (LPR) after cycles of STI. METHODS: 20 CHI patients (CD4+ > 500/mm(3), BVL > 5000 copies/mL) treated with D4T+ 3TC +IND for 5 |
| 536-M | Viral Rebound after Suppression with HAART: Experience from 237 People with Viral Load < 50 copies/mL Followed for up to 4.4 Years Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 536-M Lampe F, Johnson MA, Loveday C, Youle M, Ransom D, Sabin C, Tyrer M, Phillips AN; Royal Free Hosp. Clin., Univ, Coll. of London, UK BACKGROUND: It is important to characterize the long-term durability of viral suppression on HAART regimens, but few existing clinical trials are sufficiently long-lasting to provide this. METHODS: We followed all 237 people from the Royal Free Hospital Clinic who were naïve to antiretrovirals when they started a HAART |
| 537-M | Sequential Broadening of HIV-1-Specific CTL Responses during Supervised Treatment Interruption in Treated Acute Infection. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 537-M Yu X, Addo MM, Fitzpatrick C, Lee P, Strick D, Goulder P, Rosenberg E, Walker B, Altfeld M; Partners AIDS Res. Ctr. BACKGROUND: Increasing evidence indicates that HIV-1-specific CD8+ cytotoxic T lymphocytes (CTL) and CD4+ T helper cells play a critical role in the control of viral replication in HIV-1 infection. However, the entire breadth and magnitude of HIV-1-specific CTL responses that can be reached in an infected individual is |
| 538-M | HIV-Specific CTL Responses do not Prevent Early Viral Rebound and Immunological Deterioration after STI in Chronic HIV Infection Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 538-M van Lunzen J, Frahm N, Schmitz J, Kuroda M, Walker B, Stellbrink HJ, Altfeld M; Univ. Hosp. Eppendorf, Hamburg, Germany BACKGROUND: It is questionable whether viral replication can be controlled by STI-induced CTL responses in chronic HIV infection. Our objective was to corellate CTL responses with viral replication after STI in patients with chronic HIV infection and sustained suppression of viremia. METHODS: Preselected patients (n=15 |
| 539-M | Effector/Memory CD8 T-Cell Dynamics in HIV-Infected Patients during HAART Discontinuation and Resumption. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 539-M D'Offizi G, Amicosante M, Montesano C, Gioia C, Topino S, Agrati C, Pucillo L, Narciso P, Poccia F; Natl. Inst. for Infectious Diseases, L. Spallanzani, Rome, Italy BACKGROUND: Since supervised treatment interruption (STI) can stimulate specific anti-HIV immune response, we evaluated the CD8 T-cell specific anti-HIV immunity (anti-GAG immune response) and the CD8 T-cell effector/memory phenotypes during a cycle of treatment interruption. METHODS: We enrolled 37 patients with effec |
| 540-T | Randomized Study of Telephone Calls to Improve Adherence to Antiretroviral Therapy Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 540-T Collier AC, Ribaudo H, Feinberg J, Mukherjee L, Fischl M, Chesney M, The ACTG Protocol 746 Team; Univ. of Washington, Seattle BACKGROUND: Antiretroviral therapy is more successful if patients follow recommended drug doses and schedules. We hypothesized that increased telephone contact with patients about medications would improve adherence to antiretroviral therapy and virologic outcome. METHODS: Randomized, open-label adherence interventiona |
| 541-T | Counseling Interventions Can Improve Adherence to Highly Active Antiretroviral Therapy: Results of a French Prospective Controlled Study Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 541-T Pradier C, Bentz L, Spire B, Tourette-Turgis C, Morin M, Fuzibet JG, Pesce A, Dellamonica P, Moatti JP; INSERM U379, Marseilles BACKGROUND: The objective was to evaluate the impact of an intervention for improving adherence to highly active antiretroviral therapies (HAART) in HIV-infected patients. Method: 244 patients were included in a prospective, controlled, randomised trial comparing a group who received a counseling intervention in additi |
| 542-T | Mock Antiretroviral Therapy Trials as an Assessment Tool for Adherence: Correlates with Subsequent HIV Suppression. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 542-T Lubelchek R, Gabler C, Berry G, Wiederhold N, Cacciabando J, Highstein G, Mundy L; Washington Univ. Sch. of Med., St. Louis, MO BACKGROUND: Adherence to combination antiretroviral therapy (ART) remains a critical goal for durable suppression of HIV replication. In an urban university woman s HIV clinic, participants eligible for ART were asked to complete a mock trial using the Medication Electronic Monitoring System (MEMS). The objective was t |
| 543-T | Predictors of Adherence and Efficacy in HIV-1-Infected Patients Treated with Abacavir/Combivir (ABC/COM) or Indinavir/Combivir (IDV/COM): Final 48-Week Data from CNA3014 Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 543-T Jordan J, Cahn P, Vibhagool A, The CNA3014 Study Team; GlaxoSmithKline, Res. Triangle Park, NC BACKGROUND: This open-label study compared the efficacy of ABC/COM vs IDV/COM (Vibhagool, IAS, 2001). Additional objectives included a comparison of adherence and determination of factors associated with adherence and HIV-1 RNA (vRNA) efficacy. METHODS: 329 HIV-1-infected, treatment naïve adults were randomized to ABC/ |
| 544-T | Predictive Value of Electronic Monitoring of HAART Adherence in Patients with Acute and Early HIV Infection. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 544-T Sanchez M, Sabundayo B, Langan S, Lindsay A, Flexner C, Margolick J; Johns Hopkins Univ. Sch. of Publ. Hlth. BACKGROUND: Adherence is a known predictor of treatment outcome with HAART, but has not been evaluated in patients with acute or early HIV infection, where better immune function may affect therapeutic response. METHODS: The predictive value of adherence scores at 2 and 4 months after HAART initiation were assessed wit |
| 545-T | Nevirapine (NVP) and Protease Inhibitor (PI)-Based Regimens in a Directly Observed Therapy (DOT) Program for Intravenous Drug Users (IDUs) Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 545-T Conway B, Prasad J, Reynolds R, Farley J, Smith N, Meade A, Devlaming S; Univ. of British Columbia, Vancouver, BC, Canada BACKGROUND: The treatment of HIV-infected IVDUs presents unique challenges, including HCV co-infection, drug interactions with methadone, and the need for high levels of adherence. Within a directly observed therapy (DOT) protocol for heroin users receiving methadone, we compared the virologic and immunologic response |
| 546-T | Low Levels of Adherence Do Not Increase Risk of HIV Drug Resistance Mutations Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 546-T D. R. Bangsberg*1, E. D. Charlebois1, R. M. Grant2, M. Holodniy3, S. Perry1, K. Nugent Conroy4, D. Guzman1, A. Zolopa4, and A. R. Moss1 Low adherence predicts early TD. Among those who continue treatment with VL>100, multiple DRM occur most frequently in highly adherent patients. Providing treatment to nonadherent patients may not accelerate the rise in population levels of multi-drug resistance due to either early TD or slower accumulation of DRM in those with VL>100. |
| 547-T | Longitudinal Assessment of the Effects of Drug and Alcohol Abuse on HIV Treatment Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 547-T Lucas G, Gebo K, Chaisson RE, Moore R; Johns Hopkins Univ. Sch. of Med., Baltimore, MD BACKGROUND: In treating HIV-infected substance abusers, it is commonly advocated that attempts to address substance abuse should precede initiation of antiretroviral therapy (ART). Yet, it is unknown if temporal changes in substance abuse activity are associated with meaningful changes in HIV treatment outcomes METHODS |
| 548-T | Early Intensification with Abacavir in Subjects at High Risk for Incomplete Suppression Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 548-T Bartlett JA, Tebas P, Bassett R, Huang W, Kuritzkes D, Reisler R, The ACTG A5064 Study Team; Duke Univ. Med. Ctr., Durham, NC BACKGROUND: Approximately 50% of HIV-infected persons beginning antiretroviral therapy (ART) achieve plasma HIV RNA levels 500 copies/mL), a population identified at high risk for incomplete virologi |
| 549-T | The Efficacy, Safety, and Immunological Changes of qd Saquinavir-Soft Gel Capsules 1600 mg /Ritonavir 100 mg plus Dual Nucleosides in Patients Who Had an Undetectable Viral Load after 3 Years of Treatment Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 549-T Cardiello P, Srasuebkul P, Hassink E, Mahanontharit A, Samor T, Worarien W, Ruxrungtham K, Cooper DA, Lange J, Phanuphak P; HIVNAT and IATEC, Amsterdam, The Netherlands BACKGROUND: In order to increase access to protease inhibitor, once-daily lower doses can be used, providing efficacy and assuring safety. We evaluated the efficacy, safety, and immunological changes of qd saquinavir-soft gel capsules (SQV-SGC) 1600 mg / ritonavir 100 mg plus dual nucleoside reverse transcri |
| 550-T | Durability of Ritonavir (RTV) plus Saquinavir (SQV) Dual Protease Inhibitor Therapy in HIV Infection: 5-Year Follow-Up Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 550-T Cameron DW, Angel JB, Ryan J, Jiang P, Rode R, Farthing C, Cohen C, Mellors J, Poretz D, Markowitz M, Ho D, McMahon D, Drennan D, Seidler T, Sun E, Japour AJ; Univ. of Ottawa, ON, Canada BACKGROUND: To estimate the true rates of clinical outcomes from a recently completed 6-year dual protease inhibitor study, Kaplan-Meier conditional survival analysis allows the demonstration of cumulative rates of viral suppression with or without rebound, virologic failure, and study discontinuation. The study object |
| 551-T | Analysis of Virological Efficacy in Randomised Trials of Antiretroviral Regimens: Drawbacks of No HIV-RNA Measurements after Premature Interruption of Therapy Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 551-T Kirk O, Law M, Pedersen C, Gulick RM, Moyle G, Phillips AN, Lundgren JD; EuroSIDA Co-ord. Ctr., Hvidovre, Denmark BACKGROUND: Follow-up is often interrupted after premature discontinuation of randomised therapy in randomised clinical trials (RCT). Drawbacks of this approach is not well determined. METHODS: 2 intent-to-treat approaches were compared using data on patients starting their initial HAART regimen in a RCT (10 RCTs, n=21 |
| 552-T | Influence of a Human Multidrug Resistance Genetic Polymorphism on Treatment Outcome in a Large Community-Based Cohort Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 552-T Dong W, Chan K, Brumme Z, Hogg R, O'Shaughnessy MV, Harrigan PR British Columbia Ctr. for Excellence in HIV/AIDS, St. Paul's Hosp., Vancouver, Canada BACKGROUND: The expression of p-glycoprotein (PGP), an efflux membrane transporter encoded by the human multidrug resistance (MDR1) gene is significantly affected by a single nucleotide polymorphism (SNP) C3435T in MDR1 exon 26. Individuals homozygous for T/T allele have ~4-fold lower PGP expression compared with CC in |
| 553-T | Positive Selection of HIV-1 Protease (PR) Prior to the Advent of Protease Inhibitor-Based Therapy Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 553-T Frost SD, Condra JH, Richman DD, Leigh Brown AJ; Univ. of California, San Diego BACKGROUND: It is unclear whether immune selection is involved in PR evolution as few CTL epitopes are known in PR. Tests using sequences obtained after the introduction of protease inhibitors (PIs) are confounded by drug-related selection pressure. We analyzed genetic variation in PR sequences obtained prior to the in |
| 554-T | The Influence of Host HLA on Antiretroviral Drug Resistance Mutation in HIV-1 Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 554-T Moore C, John M, James I, Mallal S; Ctr. Clin. Immunology and BioMed. Statistics, Perth, Australia BACKGROUND: Antiretroviral treatment (ART) to induced mutations in HIV-1 reverse transcriptase (RT) and protease that allow viral escape from drug suppression are well characterised. Similarly, host CTL responses select viral variants that can escape CTL responses. We have shown in a large population study, that CTL es |
| 555-T | Co-Existence and Co-Evolution of Viral Populations with Distinct Genotypes in Patients Failing Treatment with Protease Inhibitors. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 555-T Charpentier C, Dwyer DE, Lecossier D, Clavel F, Hance AJ; INSERM U552, Paris, France BACKGROUND: The acquisiton of viral resistance to protease inhibitors results from the accumulation of resistance mutations, but little data are available concerning the evolutionary pathway(s) followed during this process. METHODS: We evaluated 7 patients failing treatment with protease inhibitors in whom a resistance |
| 556-T | HIV Drug Resistance Profiles and Clinical and Virologic Outcomes among HIV-Infected Subjects with Stable Detectable Plasma Viral Loads < 1000 Copies/mL for at least 12 Months. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 556-T E. P. Coakley*, J. P. Doweiko, N. A. Bellosillo, E. M. D'Agata, and M. A. Albrecht In HIV-infected SBJs antiretroviral therapy may result in a LLV sustained < 1000 copies/mL for prolonged periods and with stable CD4 cell counts. The frequency of GAR in this setting was, however, high (90%). Compared to nonPGSRs, PGSRs were more commonly observed to have ADR to all on-treatment drugs, greater rises in PVLs at 12 months and lower preentry nadir CD4 counts. In SBJs with stable LLV these data highlight the potential utility of GAR testing. |
| 557-T | Hypersusceptibility to Protease Inhibitors Associated with Mutated Proteases at Codons 30 and 88 in Treated Patients. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 557-T V. Obry, E. Race*, M. Vray, J. L. Meynard, L. Morand-Joubert, D. Descamps, F. Brun-Vezinet, and F. Clavel for the ANRS 088 NARVAL Study Team Hypersusceptibility to amprenavir and ritonavir is a frequent feature of viruses with mutations at codons 30 and/or 88. While HS to amprenavir is mostly promoted by mutations N88S/T, HS to ritonavir is mainly associated with genotypes bearing D30N in the absence of codon 88 mutation. |
| 558-T. | Correlation of Phenotypic Resistance and Virologic Response to Indinavir/Ritonavir Boosted Regimens Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 558-T Rice H, Zolopa A, Coram M, Murlidharan U, Shulman N, Vaamonde C, Condra JH, Hellmann NS, King H, Bates M; Stanford Univ., Palo Alto, CA BACKGROUND: Ritonavir (RTV) boosting of indinavir (IDV) results in an enhanced pharmacokinetic profile, improved dosing convenience, and increased potency. We evaluated the degree of phenotypic resistance to IDV that could be overcome with RTV boosting in a clinical |
| 559-T | Quantitative Estimate of the Effect of Individual Baseline Mutations in HIV Protease on the Virologic Response to Lopinavir/Ritonavir Therapy in Heavily Antiretroviral-Experienced Patients. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 559-T Isaacson J, Kempf D, Calvez V, Cohen-Codar I, Descamps D, Guillevic E, Bernstein B, Sun E, Chauvin JP, Rode R; Abbott Labs., Abbott Park, IL BACKGROUND: The baseline lopinavir mutation score (number of mutations at positions 10, 20, 24, 46, 53, 54, 63, 71, 82, 84, and 90 in HIV protease) is useful for predicting the virologic response to lopinavir/ ritonavir (LPV/r) therapy in ARV treatment-experienced patients. |
| 560-T | Influence of Genotypic Resistance on the Viral Load Response of 167 Patients on Lopinavir/r (LPV/r) including an Analysis of New Protease Inhibitor Resistant Mutations in 21 Patients who Failed Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 560-T Loutfy M, Thompson C, Trpeski M, Kovacs C, Rachlis A, Goodhew J, Rubin G, Gough K, Walmsley S; Univ. of Toronto and St. Michael's Hosp., Toronto, ON, Canada BACKGROUND: LPV has a high barrier to resistance. No specific mutations (muts) has been found to confer LPV resistance. METHODS:To determine the effect of resistance on VL response to LPV/r and to analyze the resistance of patients who have failed LPV/r, a retrospective study of patients in the LPV/r EAP in 4 Toronto H |
| 561-T | Impact of Gag Sequence Polymorphisms on HIV-1 Resistance to Protease Inhibitors. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 561-T Carron de la Carriere L, Mammano F, Clavel F; INSERM U552, Hosp. Bichat, Paris, France BACKGROUND: Mutations in Gag cleavage sites are known to substantially affect HIV susceptibility to protease inhibitors (PI) in the context of protease (PR) resistance mutations. Little is known, however, on the impact of natural Gag polymorphisms and the role of Gag mutations outside of the cleavage sites in PI resist |
| 562-T | Resistance to Tipranavir is Uncommon in a Randomized Trial of Tipranavir/Ritonavir (TPV/RTV) in Multiple PI-Failure Patients (BI 1182.2). Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 562-T Schwartz R, Kazanjian P, Slater L, Hathaway B, Markowitz M, Wheeler D, Goldman M, Drulak M, McCallister S, Mayers D; Associates in Res., Fort Myers, FL BACKGROUND: TPV is the first in a new class of non-peptidic protease inhibitors (NPPIs) with potent in vitro activity against broadly PI-resistant HIV-1 strains. This open-label phase II trial consisted of 2 TPV/RTV dosing regimens (low dose: TPV 500 mg/RTV 100 mg BID; high dose TPV 1000 mg/RTV 100 mg BID). TPV was ini |
| 563-T | Molecular Mechanism of I50V, I54L, and I54M Resistance to Amprenavir and Other HIV-1 Protease Inhibitors Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 563-T Xu R, Andrews W, Spaltenstein A, Danger D, Dallas W, Carter L, Hanlon M, Wright L, Furfine E; GlaxoSmithKline, Res. Triangle Park, NC BACKGROUND: The mutation I50V confers resistance to APV and minimal resistance to other clinically utilized HIVPIs. Similarly I54L and I54M confer resistance to APV in vivo, but this pathway is observed less frequently than I50V. We studied the molecular mechanism of I50V, I54L, and I54M virus resistance to |
| 564-T | Antiretroviral Resistance in ACTG 388 Participants with Virologic Failure. Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 564-T Erice A, Ribaudo H, Demeter LM, Eshleman SH, Hammer S, Hellmann NS, Fischl M, The ACTG 388 Resistance Study Team; Univ. of Minnesota, Minneapolis BACKGROUND: ACTG 388 was a randomized study comparing 3TC +ZDV with IDV, EFV+IDV, or NFV+IDV in HIV-infected subjects with 200 CD4 cells/mm(3) or HIV RNA > 80,000 copies/mL, and no previous or limited antiretroviral therapy. A lower rate of virologic failure was seen with EFV+IDV (p=0.04), and a higher rate with NFV+ID |
| 565-T | Longitudinal Analysis of RT and Protease Mutations among Israeli Patients Infected with HIV Subtype C Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 565-T Grossman |