10th Conference on Retroviruses and Opportunistic Infections


Boston, MA USA - February 10 -14, 2003

Cite as: Conf Retroviruses Opportunistic Infect. 2003 Feb 10-14;10th:Abstract No. xx

1 From HERV to HIV: Evolution of Human Retroviruses
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 1
J Coffin
Our results to date imply a large population of replicating virus, which becomes very diverse with time, but is subject to significant purifying selective forces that serve to stabilize the diversity. Implications of these results for the evolution of drug-resistant virus will be discussed.
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Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 2

Abstract not available.
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Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 3

Abstract not available.
4 Session 2 - Plenary Lecture: Preventing New HIV Infections in the U.S.: What Can We Hope to Achieve?
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 4
Valdiserri RO; CDC, Atlanta, GA
It is estimated that between 850,000 and 950,000 persons in America are living with HIV or AIDS. Given the growing number of persons living with HIV in the U.S., medical care providers have an important, ongoing role to play in reinforcing prevention messages and offering diagnosis and treatment for other STDs to "high risk" patients, e.g., those who are not involved in stable monogamous relationships. Recent work has shown that it is possible to improve HIV/STD risk assessment and counseling rates in a "real world" setting with a relatively non-intensive intervention. Given the increasing importance of prevention for HIV seropositives, care providers can make a substantial contribution to reducing new infections and achieving national prevention goals.
5 Session 3 - Plenary Lecture: HIV Vif and the Evasion of Host Anti-viral Resistance.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 5
Malim MH; King's Coll London, UK
The HIV Vif protein is a positive regulator of infection that is essential for virus growth in cultured T-cells. Vif has also been shown to be required for pathogenic lentivirus infections in animal model systems and is, therefore, presumed to be necessary for HIV-induced disease in infected persons.
6 In Vitro Characterization of Novel Benzophenone Non-nonucleoside Reverse Transcriptase Inhibitors.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 6
Chan J, Ferris R, Roberts G, Short S, Weaver K, Hazen R, Creech K, Clair MS, Dornsife R, Freeman G, Tidwell J, Romines K, Schaller L, Cowan J, Boone L
Benzophenone analogues GW4751, GW4511, and GW3011 are potent new NNRTIs active against both wild-type virus and a broad-spectrum of NNRTI-associated mutant viruses including those known to be highly resistant to currently available NNRTIs. The mutations selected during passage with GW4511 are known to be associated with NNRTI resistance.
7 RO033-4649: A New HIV-1 Protease Inhibitor Designed for Both Activity Against Resistant Virus Isolates and Favorable Pharmacokinetic Properties.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 7
Cammack N, Swallow S, Heilek-Snyder G, Lie Y, Parkin N, Kohli A
RO033-4649 is a potent and selective HIV-1 protease inhibitor with promising activity against PI-resistant HIV isolates. Phase I clinical evaluation has commenced.
8 First Clinical Results on Antiretroviral Activity, Pharmacokinetics, and Safety of TMC114, an HIV-1 Protease Inhibitor, in Multiple PI-experienced Patients.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 8
Arasteh K, Clumeck N, Pozniak A, Jaeger H, Pauw MD, Muller H, Peeters M, Hoetelmans R, Meyer SD, van der Sandt I, Comhaire S, van der Geest R
TMC114/r exhibited potent antiretroviral activity and favorable pharmacokinetics when given for 14 days to multiple PI-experienced pts currently failing a PI-containing regimen. For the TMC114/r arms, maximum and median changes in HIV-1 RNA (log10) were -2.49 and -1.35 copies/ml, respectively. TMC114/r was generally well tolerated.
9 Pyranodipyrimidines: A New Class of HIV Integrase Inhibitors that Block Viral Replication in Cell Culture.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 9
Debyser Z, Pannecouque C, Pluymers W, Maele BV, Vercammen J, Tetz V, Engelborghs Y, Clercq ED, Witvrouw M; Rega Inst for Med Res, Katholieke Univ Leuven, Belgium
Based on their mode of action, e.g., inhibition of an HIV integration step that is different from both clinically approved anti-HIV drugs as well as other IN inhibitors such as the diketo acids, PDPs can be considered as candidate drugs to be further pursued in their own right and in drug combination regimens for the therapy of HIV infections.
10 AK602: A Novel HIV-specific Spirodiketopiperazine CCR5 Inhibitor Potent Against a Wide Spectrum of R5-HIV.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 10
Maeda K, Nakata H, Miyakawa T, Ogata H, Koh Y, Shibayama S, Sagawa K, Takaoka Y, Moravek J, Koyanagi Y, Mitsuya H; Kumamoto Univ Sch of Med, Japan
The present data strongly suggest that AK602 can potently block the infectivity and replication of a wide spectrum of R5-HIV with partial inhibition of CC/CCR5 interactions. Considering the possibility that the long-term inhibition of CC/CCR5 interactions could lead to compromised inflammation/immune reaction, the present data warrant further development of AK602 as a potential HIV-specific CCR-inhibiting therapeutic for HIV infection.
11 Anti-HIV-1 Activity of TAK-220, a Small Molecule CCR5 Antagonist.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 11
Iizawa Y, Kanzaki N, Takashima K, Miyake H, Tagawa Y, Sugihara Y, Baba M
TAK-220 is an orally bioavailable CCR5 antagonist with a potent anti-R5 HIV-1 activity, indicating a promising candidate as an anti-HIV-1 drug.
12 UK-427,857, a Novel Small Molecule HIV Entry Inhibitor is a Specific Antagonist of the Chemokine Receptor CCR5.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 12
Dorr P, Macartney M, Rickett G, Smith-Burchnell C, Dobbs S, Mori J, Griffin P, Lok J, Irvine R, Westby M, Hitchcock C, Stammen B, Price D, Armour D, Wood A, Perros M
UK-427,857 is a prototype CCR5 antagonist for the treatment of HIV infection, with excellent potency against lab-adapted and primary strains. The predicted pharmacokinetic and safety profile of the candidate are such that the compound has the potential to block receptor binding akin to the naturally protective Δ32-CCR5 homozygous phenotype, when administered to humans with one or more wt-CCR5 alleles.
13 Safety and Preliminary Anti-HIV Activity of an Anti-CD4 mAb (TNX-355; Formerly Hu5A8) in HIV-infected Patients.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 13
Kuritzkes DR, Jacobson JM, Powderly W, Godofsky E, DeJesus E, Haas F, Reimann KA, Yarbough P, Curt VR, Shanahan WR
Single doses of the novel entry inhibitor TNX-355 were well tolerated and acutely reduced viral load in HIV-1-infected patients. Further assessment of therapeutic potential awaits data from longer duration trials; a phase 1b multiple-dose study is planned.
14 Relationship between P-glycoprotein and HIV-1 Receptors in Peripheral Blood Lymphocytes and Cell Lines.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 14
Owen A, Hoggard PG, Chandler B, Khoo SH, Back DJ
The relationship between Pgp and HIV-1 co-receptor expression in PBLs from healthy volunteers indicates that there may be similar mechanisms involved in the control of these proteins. This is an important finding since PIs are substrates for Pgp, raising the possibility that cells expressing higher levels of Pgp (and, therefore, virus sanctuary) may place a selective pressure in favour of X4 tropic virus.
14lb T-1249 Demonstrates Potent Antiviral Activity over 10 Day Dosing in Most Patients who Have Failed a Regimen Containing Enfuvirtide (ENF): Planned Interim Analysis of T1249-102, a Phase I/II Study.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 14lb
Miralles GD, Lalezari JP, Bellos N, Richmond G, Zhang Y, Murchison H, Spence R, Raskino C, DeMasi RA
The results of this interim analysis suggest that T‑1249 demonstrates potent short-term suppression of plasma HIV RNA in most patients who harbor ENF-resistant viruses.
15 Mannose-specific Lectins as Novel Microbicides against HIV?
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 15
Schols D, Hatse S, Vermeire K, Princen K, Peumans W, Damme EV, Clercq ED, Balzarini J
Mannose-specific plant lectins proved markedly inhibitory to all HIV variants that were examined. They most likely interfere with viral entry. Their broad-spectrum anti-HIV activity makes them potential clinical candidates as anti-HIV microbicides to prevent the sexual transmission of AIDS.
16 A Novel Microbicide that Prevents Intravaginal Transmission of SIV
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 16
Z. Ambrose*1, C. Miller2, L. Compton2, J. Hildreth3, J. Lifson1, V. KewalRamani1
Should BCD continue to prevent SIV transmission and not perturb mucosal tissues in this model, its current approved use in humans suggests it would be an important candidate for clinical consideration for use as an anti-HIV microbicide.
17 Inside-out Regulation of HIV-1 Particle Fusion.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 17
Aiken C, Wyma DJ, Lineberger JE, Miller MD
We have identified a novel mechanism for regulating HIV-1 entry through coupling membrane fusion activity to core maturation via binding of the gp41 cytoplasmic domain to Pr55Gag. These findings have implications for therapeutic strategies targeting HIV-1 entry and for HIV-1 vaccine development.
18 Disruption of Lipid Rafts in HIV-producing Cells Impairs Fusion of HIV-1 Virions To Target Cells.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 18
Cavrois M, Yonemoto W, Fenard D, Neidleman J, Greene W
These findings demonstrate that fusion of HIV virions to target cells is markedly impaired when lipid rafts are disrupted in the producer cells, suggesting a possible facilitating role for cholesterol or other raft components in the fusion reaction. Further, the enhancement by Nef of viral infectivity cannot be explained by intrinsic differences in the fusogenic properties of HIV-wt and HIVΔNef virions.
19 Mutations in the Cytoplasmic Domain of the SIV Transmembrane Molecule can Dramatically Increase Envelope Content in Virions, Infectivity, and Resistance to Antibody-mediated Neutralization.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 19
Yuste E, Desrosiers R
Our results indicate that the sequences present in the cytoplasmic domain of gp41 can dramatically influence env content in virions and that env content in virions is an important determinant of relative sensitivity to antibody-mediated neutralization.
20 Recruitment of CD4, CCR5, Rafts, and Ezrin in Actin-dependent Cell Surface Structures: Implications for HIV Fusion and Entry Events.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 20
C.M. Steffens, T.J. Hope
Current models of HIV entry suggest that multiple receptor and co-receptor molecules are needed to interact with each envelope trimer, and that multiple trimers are necessary for fusion to occur. Our observation that CD4, CCR5, ezrin, and GM1 are all present in the same actin-dependent structures may unify previous reports that lipid rafts and actin are important in facilitating the interactions leading up to HIV fusion and entry.
21 In Vitro De-evolution of the HIV Envelope Glycoprotein to Functional Core Elements with Deletions of V1/V2 and V3 Hypervariable Loops.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 21
Lin G, Haggarty BS, Romano J, Vance PJ, Hoxie JA; Univ of Pennsylvania, Philadelphia
These results demonstrate that functional HIV Env variants can be generated lacking V1/V2 and the majority of V3 and may represent a primordial Env core. Variable loops may have evolved to evade humoral immune responses. Thus, functional Env cores with variable loop deletions may serve as better immunogens in eliciting novel immune responses against conserved regions on the gp120 core.
22 A Novel Potent CD4-induced Monoclonal Antibody (E51) Active against Primary HIV-1 Strains.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 22
Xiang SH, Abreu M, Robinson J, Sodroski J; Dana-Farber Cancer Inst, Boston, MA
The binding site of CD4-induced (CD4i) antibodies on the gp120 envelope glycoprotein of HIV-1 is known to overlap with the binding site for co-receptors. Most CD4i antibodies exhibit only weak neutralizing activity against HIV-1 isolates, which have evolved mechanisms to resist these antibodies. Additional
23 Sensitivity of HIV-1 to Entry Inhibitors Correlates with Envelope: Co-receptor Affinity, Co-receptor Density, and Fusion Kinetics.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 23
Reeves J, Gallo S, Ahmad N, Miamidian J, Harvey P, Sharron M, Pohlmann S, Pierson T, Biscone M, Sfakianos J, Derdeyn C, Tomaras G, Blumenthal R, Hunter E, Doms R; Univ of Pennsylvania, Philadelphia
Co-receptor density and Env mutations that affect receptor engagement and membrane fusion rates can alter entry inhibitor sensitivity. Since co-receptor expression levels are often limiting for virus in vivo, individuals expressing lower levels may respond more favorably to entry inhibitors such as T-20, whose effectiveness we show is dependent in part on fusion kinetics.
24 The Role of ESCRT-I in Retroviral Budding.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 24
Martin-Serrano J, Zang T, Bieniasz PD; Aaron Diamond AIDS Res Ctr, Rockefeller Univ, New York, NY
These results indicate that all 3 classes of retroviral L-domains require a functioning class E VPS pathway in order to effect budding. However, the PTAP-type L-domain appears unique in its requirement for an intact, or nearly intact, ESCRT-I complex.
25 Cleavage at the N-terminus of the HIV Protease is Modulated by the Beta-sheet Structure of the Dimer Interface.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 25
Kaplan AH, Pettit SC; Univ of North Carolina Sch of Med, Chapel Hill
Overall, our data suggest a model for virus assembly in which the initial GagPol cleavages are accomplished in cis and indicate a structural mechanism by which release of the more active mature protease is delayed until later in virus assembly. We present a model that integrates protease activation and GagPol dimerization into virus particle assembly. Our data also suggest novel avenues for the design of protease inhibitors.
26lb PML and the Proteasome as Mediators of Intracellular Antiretroviral Innate Immunity
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 26lb
P. Turelli, D. Trono
PML and the proteasome are the mediators of an intracellular innate antiviral response that limits the susceptibility of human cells to infection by HIV and certain oncoretroviruses. Because "N-tropic" and "B-tropic" MLV strains differ only by a few amino acids in Capsid (CA), it is likely that this retroviral constituent is targeted by this response in both HIV and MLV.
27 Stoichiometry of Neutralization of a HIV-1 Primary Isolate by the Anti-CD4 Binding Site Antibody b12s.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 27
Franti M, Frost S, Vivona V, Delgado K, Ramos L, Burton DR, Poignard P; Scripps Res Inst, La Jolla, CA
The results suggest that, similar to the mechanism proposed for antibody neutralization of TCLA isolates, neutralization of primary isolates is the result of antibody-coating of virions.
28 Tyrosine Sulfation of Human Antibodies that Bind the CCR5-binding Domain of HIV-1 gp120.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 28
Choe H, Li W, Wright P, Moore M, Vasilieva N, Robinson J, Sodroski J, Farzan M; Harvard Med Sch, Cambridge, MA
These antibodies are derived from individuals who effectively control HIV-1 replication, and they potently neutralize R5 isolates. Therefore, tyrosine sulfated anti-gp120 antibodies of this class may be useful in slowing or preventing infection.
29 Migration of T-cells Away from HIV-1 gp120: A New Mechanism for Viral Immune Evasion.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 29
Brainard DM, Tharp WG, Olszak IT, Trocha A, Kalams SA, Walker BD, Wyatt R, Sodroski J, Poznansky MC; Partners AIDS Res Ctr, Harvard Med Sch, Boston, MA
CTL migration contributes to the efficacy with which HIV-specific CTL kill target cells. HIV gp120 dysregulates immune cell localization in vitro. The distinct phenomenon of movement away from a chemokine or chemokinetic agent such as gp120, which we term fugetaxis (fugere: to flee from; taxis: movement) represents a novel mechanism of regulating the movement of mature T-cells away from specific sites and may provide a mechanism by which HIV evades challenge by immune effector cells in vivo. Novel treatment strategies might be developed based on inhibiting the effect of HIVgp-120 on the migration of HIV-specific CTLs.
30 Expression of Lymphocyte Homing Receptors by SIV-specific CD8+ T-cells in the Female Reproductive Tract of Rhesus Macaques.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 30
M. Cromwell1, X. Alvarez2, J. Altman3, S. Westmoreland1, S. Klumpp1, A.Luster4, A. Lackner2, P. Johnson1
These results indicate that SIV-specific T-cells are enriched in the CD8+ T-cell population of the female genital mucosa compared to peripheral blood. Expression of inflammatory chemokines such as CXCL9 may provide signals directing the trafficking of T-cells to the female reproductive tract.
31 Comprehensive Analysis of HIV-specific CD4 Responses by IFN-gamma ELISpot in Early Chronic HIV-1 Infection Shows Marked Immunodominance of gag and nef and the Presence of Broadly Recognized Peptides.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 31
D. Kaufmann1, P. Bailey1, L. Cosimi2, P. Norris1, M. Addo1, M. Altfeld1, H. Truong1, M. Johnston1, C. Brander1, B. Walker1, E. Rosenberg1
Our analyses show that HIV-specific CD4 responses could be identified in the majority of the studied individuals with a wide spectrum in breadth and magnitude and an immunodominance of gag and nef. The paucity of CD4 responses to other proteins contrasts with the pattern of CD8 responses in the same subjects with broad responses to other proteins. The high frequency of responses to a limited subset of peptides suggests a focused recognition of peptides, which may be promiscuously presented by different HLA Class II alleles. These findings may have significant impact for the design of immunotherapeutic strategies.
32 Functional Discrepancies in HIV-specific CD8+ T-lymphocyte Populations Reflect the Kinetics of Virus Exposure.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 32
Price DA, Oxenius A, Sewell AK, Dawson SJ, Guenthard HF, Fischer M, Gillespie GM, Rowland-Jones SL, Koup RA, Fagard C, Hirschel B, Douek DC; Vaccine Res Ctr, NIH, Bethesda, MD
The proportion of CD8+ T-lymphocytes that exhibit an impaired functional phenotype directly ex vivo in populations expressing TCRs specific for individual HIV-derived antigens is related to pVL. These findings have implications for the interpretation of quantitative data generated by methods that rely on functional readouts.
33 Relationship Between Functional and Qualitative Abnormalities within the Pool of HIV-1 Specific Memory CD4 T-cells and Control of HIV-1 Disease.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 33
A. Harari, S. Petitpierre, M. Khonkarly, P. A. Bart, G. Pantaleo
These results demonstrate an abnormal composition of the pool of HIV-specific CD4 T-cells and a selective IL-2 defect of the HIV-specific memory CD4 T-cells in both blood and LN. These parameters represent correlates of immune protection better than CD4 T-cell proliferation.
34 Systematic Microarray Analysis Reveals Counter Balance between Perforin and Interleukin 7 Receptor with Progression of HIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 34
F. Boutboul1, D. Puthier2, C. Nguyen2, H. Ait Mohand3, C. Katlama3, G. Carcelain1, P.Debré1, I. Hirsch4, B.Autran1
Systematic microarrays analysis allows global analysis of mechanisms of immune cells alterations during HIV infection and highlights new aspects so far misunderstood of CD8 T-cell homeostasis.
35 Vigorous HIV-specific CD8 T-cell Responses in Late Stage HIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 35
R. Draenert*1, Y. Tang1, C. Verrill1, A. Wurcel1,2, M. Boczanowski1, A. Rathod1, M. Addo1, B. Walker1
Unexpectedly broad and strong IFN-γ+ CD8 T-cell responses persist despite progressive chronic HIV infection with high viral loads and low CD4 counts. The lack of viral escape coupled with defects in full maturation suggest that in vivo defects in CD8 T-cell function play a major role in lack of efficacy in this cohort.
36 HIV Transmission Risk Behaviors Among HIV-infected Individuals Released from Prison.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 36
Wohl DA, Shain L, Adamian M, Stephenson BL, Strauss R, Golin C, Kaplan A; Univ of North Carolina, Chapel Hill
Immediately following prison release a significant proportion of HIV-infected former inmates engage in behaviors with high risk of transmitting HIV and may play a significant role in the transmission of the virus within the communities to which they return. There is an urgent need for the development of interventions to reduce HIV transmission risk behaviors of HIV-infected releasees.
37 The Internet and High-risk Sex among Men Who Have Sex with Men.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 37
M. A. Chiasson1, S. Hirshfield*1, M. Humberstone1, J. DiFilippi1, D. Newstein1, B. Koblin2, R. Remien3,4
The very high risk sexual behavior and the significant association between meeting a sex partner online and UAS, particularly for HIV+ men, found in this study provide additional evidence that the Internet may play a role in HIV transmission. Similar to other high risk venues of the 1970s and 1980s (e.g., bath houses and back rooms), the Internet may be a setting in which to meet new sex partners and potentially transmit HIV. Our success in rapidly recruiting a large number of men reporting very high-risk sexual behavior from a single Internet site suggests that this recruitment method can also be used to provide urgently needed safer sex messages.
38 HIV Incidence, Prevalence, and Behavior of Inner City Individuals Attending the Johns Hopkins Emergency Department.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 38
C. Henson1, O. Laeyendecker2, B. J. Horne1, R. E. Rothman1, G. D. Kelen1, J. B. Shahan1, K. Ketlogetswe1, T. C. Quinn2
These results suggest that inner city EDs may provide an opportunity to identify previously unrecognized HIV infection and, together with incidence testing, allow for "real-time" monitoring of the epidemic. In addition, the ED could serve as a venue for disseminating information to at risk individuals. Finally, this data represents an increase of both incidence (1.19% vs 0.72% per yr) and prevalence (11.3% vs 8.9%) in this population from last year's study.
39 The High Yield of Routine HIV Screening in Urgent Care Sites in Massachusetts.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 39
R. P. Walensky1,2, E. Losina3, L. Malatesta4, G. Barton4, J. F. McGuire4, K. A. Freedberg1
Think HIV, an urgent care center-based routine voluntary HIV CTR program, had a significantly higher yield than regular self-referral testing. Routine HIV testing will lead to identification of HIV-infected persons who do not describe themselves as high risk for infection. Further efforts to expand such programs nationally are essential.
40 HIV-1 Transmission per Coital Act, by Stage of HIV Infection in the HIV+ Index Partner, in Discordant Couples, Rakai, Uganda.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 40
Wawer MJ, Serwadda D, Li X, Quinn TC, Sewankambo NK, Kiwanuka N, Kigozi G, Gray RH; Columbia Univ, New York, NY
Objective: To determine the rates of HIV-1 transmission per coital act in discordant couples in rural Rakai District, Uganda , by the stage of HIV infection in the index HIV + partner. METHODS: A total 240 HIV discordant couples (217 with HIV prevalent index partners and 23 with HIV incident index partners) in which th
41 Sorting Out Serosorting with Sexual Network Methods.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 41
J. McConnell1 , R. Grant1,2
Serosorting by HIV-infected individuals can be investigated using network methodology, which elucidates patterns of contact that underlie the epidemic spread of infectious diseases. High levels of serosorting may limit the impact of risky sex on the spread of the epidemic, although serodisclosure was only reported in 1/2 of partnerships. Further research is needed to identify determinants of serodisclosure and serosorting, and to assess the impact of recent reports of HIV-1 superinfection on these epidemiologically important network characteristics.
42 Post-exposure Prophylaxis After Sexual Assault In South Africa.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 42
Wulfsohn A, Venter WD, Schultze D, Levey M, Sanne IM; Johannesburg, South Africa
In this group, despite a high incidence of multiple-assailant assault and a high background prevalence of HIV, only a single seroconversion was documented in treated returning patients. A seroconversion in a pt who did not receive PEP implies that transmission via sexual assault is possible. The South African government has agreed to make HIV post-exposure prophylaxis broadly available in the country, with the first sites becoming operational in mid-2002.
43 Sustained Use of Antiretroviral Therapy Reduces Mortality among HIV-infected Homeless and Marginally Housed Individuals Living in San Francisco.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 43
E. D. Riley1, D. R. Bangsberg1, D. Guzman1, S. Perry2, A. Moss1
Among San Francisco's HIV-infected homeless and marginally housed, 74% received HAART. Even in a cohort with a history of 65% adherence, we found that sustained treatment substantially reduced mortality. While adherence remains an issue, HAART has had a significant effect on mortality in this population.
44 Incidence and Prevalence of Diabetes Mellitus among HIV-infected Patients in Northern California's Largest HMO.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 44
G. N. DeLorenze1, M. Horberg2, A. J. Karter1, A .Ferrara1, C. P. Quesenberry1, A. L. Tsai1
These results suggest that the elevated incidence of DM in the NC-KPHP HIV+ population may be attributable to the introduction of PIs in 1996, but that iatrogenic effect diminished in subsequent years, most likely due to a change in PI prescribing patterns.
45 The Evolving Epidemic of HIV/AIDS in Eastern Europe.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 45
S Matic
More intensive and far-reaching interventions are urgently required to combat TB in Africa, Asia, and Latin America where HIV is rapidly undermining all efforts to contain disease rates.
46
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 46

Abstract not available.
47 Prevention and Care of HIV-infected Women in Sub-Saharan Africa.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 47
Mbori-Ngacha D; Univ Nairobi and Global AIDS Program, CDC, Kenya
BACKGROUND:The HIV/AIDS epidemic has reached previously unimagined levels. The worst affected region being Sub-Saharan Africa home to 80% of all HIV infected people in the world. As the epidemic has matured the vulnerability of women has come to the fore. Current statistics from UNAIDS indicate that women constitut
48 Use of Antiretroviral Therapy in Developing Countries: A Biosocial Analysis.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 48
Farmer P; Brigham and Women's Hosp and Partners In Health, Boston, MA
Over 95% of the burden of HIV disease is to be found in resource-poor settings, but to date there have been almost no donor-funded programs seeking to integrate HIV prevention efforts with the full range of therapeutic options required to treat advanced HIV disease effectively in such settings. With a GNP o
48a The Second Exon of SIVmac239 Tat Contributes to Chronic Viral Replication and Disease.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 48a
Smith SM, Klase Z, Pentlicky S, Neuveut C, Marx P, Jeang KT; St Michael's Med Ctr, Newark, NJ
The Tat proteins of HIV/SIV are encoded by 2 exons. The role of the 2nd exon of HIV or SIV Tat has not been evaluated in vivo. METHODS: We constructed a clone (SIVtat1ex) of SIVmac239, which encodes for only the 1st exon of Tat, and studied it in vivo. Codons 96 and 97 were changed from GCA TCA to TGA TAA.
S48a Grand Challenges in AIDS and Global Health.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10:Session 9b Plenary Lecture 48a
Klausner RD; Bill & Melinda Gates Fndn, Seattle, WA
Extensive data demonstrate the disproportionate impact of infectious disease on the developing world, yet only 10% of research dollars are spent on the diseases and conditions that cause 90 percent of the world s health burden. A major focus of the Bill & Melinda Gates Foundation is to reduce inequities
49 RNAi: Ancient Pathways Programmed by Small RNAs.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 49
Zamora P; Univ of Massachusetts Med Sch, Worcester
Double-stranded RNA can now be used in a wide variety of eukaryotes to suppress the expression of any gene, allowing rapid analysis of that gene s function, a technique known as RNA interference (RNAi). How cells use the information in double-stranded RNA to suppress gene expression and why they contain the
50 Designing RNA I-based Therapeutic Strategies for HIV.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 50
Rossi JJ, Lee NS, Li M, Li H, Gu S, Kim J, Bauer G, Castanotto D, Pfeifer G, Tommas S, Bannerjie A, Akkina R; Beckman Res Inst of the City of Hope, Duarte, CA,
The recent discoveries of RNA interference in mammalian cells has prompted the development and testing of RNAi based approaches for the treatment of HIV-1 infection. We have been exploring the use of lentiviral vector mediated transduction of anti-HIV-1 siRNA encoding genes into hematopoietic progenitor cel
51 Some Steps Towards Moving RNA Interference to the Clinic.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 51
Lieberman J; Ctr for Blood Res, Harvard Univ Med Ctr, Boston, MA
RNA interference (RNAi) is an ancient evolutionarily conserved mechanism to protect the genome from damage by viruses and other insertable genetic elements. Recently we and others have harnessed RNAi to inhibit HIV infection in cell lines in vitro. Many steps are needed to develop RNAi as a therapeutic tool
52 Using RNA Interference to Inhibit HIV-1 Replication and Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 52
Cullen BR; Howard Hughes Med Inst, Duke Univ Med Ctr, Durham, NC
RNA interference (RNAi) represents a powerful technique to silence individual genes in human cells. Because RNAi probably evolved as an antiviral defense and is clearly important in this regard in plants, it seems possible that RNAi could be used as an antiviral treatment in humans. As an initial test of th
53 Genetic Condoms of HIV-1 Infection: Using Host Genetics to Dissect HIV-1 Pathogenesis.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 53
Ahuja S; Univ of Texas, San Antonio
Abstract not available.
54 HIV Adaptation to the Genetic Polymorphism of the Host.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 54
Mallal S; Royal Perth Hosp, Australia
Host genetics influence the clinical outcomes of HIV disease at multiple levels: establishment of infection, HIV viral load, CD4 T-cell decline, specific OIs and malignancies, and response to and complications of therapy. The exposure variable of interest may be the same in all patients (pts), as in the exa
55 Influence of the KIR genes on HIV-1 Disease.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 55
Carrington M; NCI-Frederick, MD
Natural killer (NK) cells are an important component of the innate immune system and provide the first line of defense in the early stages of the immune response against viral infections, by production of cytokines, and direct cytotoxicity. Method: The killer immunoglobulin-like receptors (KIR) on NK cells
56 Comparison of Effects on Infection and Disease Progression.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 56
Kaslow RA, Tang JJ, Dorak MT; Univ of Alabama at Birmingham
Specific sequence variants in human gene systems have been increasingly associated with the ease of HIV-1 transmission and/or the level of viremia or rate of disease progression. Some of these effects of human genetic polymorphisms on HIV/AIDS are now well established while others are less certain. A critic
57 The Changing Incidence of Clinical AIDS Events in 12,574 Treatment-naïve Patients Starting HAART.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 57
Sabin C, D'Arminio Monforte A, May M, Grabar S, Reiss P, Lundgren J, Justice A, Staszewski S, Leport C, Dabis F, Montaner JS, Johnson M, Gill MJ, Fatkenheuer G, Egger M; Royal Free and Univ Coll Med Sch, London, UK
Although the use of HAART has led to a dramatic decline in the incidence of clinical AIDS-defining events, it is unclear whether rates of decline are similar for events of different aetiologies. METHODS: The ART Cohort Collaboration includes data on 12,574 treatment-naïve patients (pts) starting HAART from
58 Analysis of Latent HIV Infection and Sequence Evolution Post Therapy in Semen and Blood Compartments.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 58
Craigo JK, Patterson B, Ding M, Montelaro RC, Mellors J, Gupta P; Univ of Pittsburgh, PA
HIV-1 RNA levels in semen and blood compartments decrease below detection limits during PI and DMP (an NNRTI) therapy. Despite these favorable therapeutic effects, it is clear that persistent reservoirs of HIV-1 capable of rebounding in the absence of drug treatment or by the evolution of escape mutants rem
59 Pegylated Interferon Alfa-2b: A New Therapeutic Option in the Treatment of Early-stage HIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 59
Schugt I, Kreuter A, Schlottmann R, Bader A, Altmeyer P, Brockmeyer NH; St Josef-Hosp, Bochum, Nordrhein-Wetsfalen, Germany
HAART has made it possible to sustain suppression of HIV type-1 replication, producing a substantial decline in AIDS incidence, mortality, and morbidity. In addition to readily controllable short-term side effects, HAART also has many long-term side effects. Thus, new therapeutic options are required. One o
60 Phase-I Study with a Therapeutic MVA-BN-Nef Vaccine in HIV-1 Infected Patients on HAART.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 60
E. Harrer1, M. Bäuerle1, B. Ferstl1, P. Chaplin2, B. Petzold2, S. Bergmann1, M. Hamacher1, J. R. Kalden1, D. Willbold3, T. Harrer1
Increasing side effects of HAART have stimulated interest in therapeutic vaccines to boost HIV-specific immunity. However, there is a lack of vaccines which can induce a strong CTL response in HIV + patients (pts). Therefore, we studied in a phase-I-study the immunogenicity and safety of the MVA-BN vector (
61 Therapeutic Vaccination with ALVAC-HIV vCP1433: A Recombinant Canarypox Vaccine in Chronically HIV-1 Infected Patients Treated with HAART: VACCITER (ANRS 094).
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 61
Tubiana R, Carcelain G, Vray M, Gourlain K, Hilpert S, Dalban C, Chermak A, Habib RE, Klein M, Costagliola D, Calvez V, Autran B, Katlama C; Pitie-Salpetriere Hosp, Paris, France
To evaluate safety, immunogenicity, and ability of ALVAC HIV vCP1433 a recombinant canarypox carrying HIV-1 genes (env, gag, epitopes of pol, nef), to control viral replication in chronically HIV-infected patients (pts). METHODS: In this pilot, open, prospective non comparative study HIV-infected pts (nadir
62 Immunological and Virological Efficacy of ALVAC-VIH 1433 and HIV Lipopeptides (Lipo-6T) Combined with SC IL-2 in Chronically HIV-infected Patients-Results of the ANRS 093 Randomized Study.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 62
Y Levy1, H Gahery-Segard2, C Durier3, A-S Lascaux1, V Meiffrédy3, C Goujard4, J-P Cassuto5, C Rouzioux6, R Elhabib7, J-G Guillet8, J-P Aboulker3, J-F Delfraissy4, ANRS 093 Study Group9
Vaccinated pts experienced a better control of HIV replication after stopping HAART. This effect is associated to the stimulation of a sustained and a polyepitopic HIV immune response.
63 Differential Modulation of Whole Blood Naive and Memory CD4+ and CD8+ T-cell Subsets by Viral Replication During Therapy Interruption in Chronically HIV-1 Infected Patients.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 63
Papasavvas E, Thiel B, Pistilli M, Mackiewicz A, Farabaugh M, Moore EC, Gallo C, Gross R, Foulkes A, Mounzer K, Schmidt L, Ondercin J, Shull J, Kostman JR, Montaner LJ; Wistar Inst, Philadelphia, PA
The modulation of naïve and memory T-cell subsets during Therapy Interruptions (TIs) in chronically HIV-1 infected patients (pts) is undetermined. METHODS: An immunology sub-study of 41 chronically HIV-infected and stably suppressed pts enrolled in a randomized trial on the effects of TI characterized chang
64 HIV-NAT 001.4: A Prospective Randomized Trial of Structured Treatment Interruption in Patients with Chronic HIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 64
J. Ananworanich1,2, P. Cardiello1,3, P. Srasuebkul1,2, T. Samor1,2, E. Hassink3, A. Mahanontharit1,2, T. Boonmangum1,2, W. Apateerapong1,2, A. Hill4, K. Ruxrungtham1,2,5, D. Cooper1,6, J. Lange1,3, P. Phanuphak1,2,5
CD4-guided and wk on-wk off strategies resulted in comparable clinical, AE and QOL outcomes to cont ARV. Proportion of pts with CD4 > 350 was similar in all arms although CD4-guided treatment had the largest CD4 count decrease. CD4-guided treatment was the best ARV cost saving strategy and had similar VL outcome to cont ARV. There were high rates of VL failures in the wk on-wk off arm; however, all had VL < 50 after continuing the same ARV regimen. Previous sub-optimal ARV prior to HAART may have contributed to STI failure.
65 A Multi-center, Randomized Controlled Clinical Trial of Continuous vs Intermittent HAART Guided by CD4+ T-cell Counts and Plasma HIV-1 RNA Levels.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 65
L. Ruiz1, L. Gómez2, P. Domingo3, J. Romeu1, G. Tambussi4, J. Martínez-Picado1, J. Miranda1, J. C. Martínez1, J. M. Llibre5, C. Tural1, G. Sirera1, F. Vidal6, CR. Fumaz1, E. Negredo1, B. Clotet1
Treatment discontinuation controlled by CD4 and viral load was safe in our study cohort. Our results show that 43% of the patients could remain without therapy for at least 48 wks.
66 ISS-PART: A Prospective, Randomized, Multi-center Clinical Trial of Intermittent Therapy in HIV+ Subjects with Persistent Suppression of Viral Replication.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 66
S. Vella , M. Giuliano, L. Palmisano, R. Bucciardini, M. Andreotti, R. Arcieri, V. Fragola, C. Galluzzo, L. Weimer, MF Pirillo, R.Amici, E.Germinario, Italian ISS-PART Clinical Centers
Overall response to therapy reinitiation was satisfactory; however, a longer follow-up is required to assess the clinical significance of mutations in the rebounding virus.
67 CPCRA 064: A Randomized Trial Examining Structured Treatment Interruption for Patients Failing Therapy with Multi-drug Resistant HIV.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 67
J. Lawrence1, D. Mayers2, K. Huppler Hullsiek3, G. Collins3, D. Abrams1, R. Reisler4, L. Crane5, B. Schmetter6, T. Dionne7, J. Saldanha8, M. Jones1, J. Baxter9, the CPCRA 064 Study Team of the Terry Beirn Community Programs for Clinical Research on AIDS.
In treatment experienced pts failing therapy with MDR virus, STIs as used in this study do not appear to confer clinical, immunologic, virologic, or QOL benefits.
68 Long-term Benefit of Treatment Interruption in Salvage Therapy (GIGHAART ANRS 097).
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 68
Katlama C, Dominguez S, Duvivier C, Delaugerre C, Peytavin G, Legrand M, Calvez V, Gourlain K, Costagliola D; Hosp Pitie Salpetriere, Paris, France
Megahaart was shown to rescue severe clinical situations and TI to favor the return of wild-type virus. Objective: To evaluate the benefit of TI in patients (pts) with multiple failure of therapy in a context of very advanced HIV disease (HIV VL > 50,000cps/ml and CD4cells
69 The Relationship Between Retroviral Integration and Host Cell Transcription 2.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 69
Maxfield L, Dow C, Coffin J; Tufts Univ, Boston, MA
Retroviral DNA integration occurs throughout the genome; however, local hot spots for integration exist where a strong preference for certain sites over others are seen. Our goal is to define properties of host cell DNA that influence sites of retroviral integration.
70 Selection of DNA Integration Sites by HIV in Human Peripheral Blood Mononuclear Cells.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 70
Mitchell R, Portier N, Schroder A, Shinn P, Chen H, Berry C, Ecker J, Bushman F; Salk Inst, Univ of California, San Diego, CA
In order for HIV to successfully replicate, the proviral DNA must integrate into human DNA. Previously we reported mapping 524 sites of HIV cDNA integration on the human genome sequence using a human T-cell line. We have extended the study by using human primary cells, peripheral blood mononuclear cells (PB
71 HIV-1 Vpr is Essential for Expression from Unintegrated HIV-1 DNA.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 71
Poon B, Chen IS; David Geffen Sch of Med at UCLA, Los Angeles, CA
Unintegrated viral DNA is generally transcriptionally inert but can be expressed under some circumstances and may play a significant role in HIV-1 pathogenesis. METHODS: We determined whether HIV-1 Vpr may be involved in mediating gene expression from unintegrated HIV-1. Cells were infected with VSV-G pseud
72 The Murine Homologue of the VIF Cellular Co-factor, APOBEC3G/CEM15, is a Potent Inhibitor of HIV-1 Replication Whose Activity is Not Blocked by HIV-1 or SIV VIF.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 72
Mariani R, Chen DS, Nymark-McMahon H, Landau NR; Salk Inst for Biological Studies, La Jolla, CA
HIV-1 replication in primary human T-cells and monocytes requires VIF. VIF is required in these cells to overcome the inhibitory activity of the cellular protein ABOBEC-3G/CEM15, a protein that belongs to a family of RNA editing enzymes. The mechanism by which APOBEC3G interferes with HIV-1 replication is n
73 Identification of a Novel SIV Lineage with a Vpu Gene in Cercopithecus Monkeys from Cameroon.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 73
Courgnaud V, Loul S, Mpoudi E, Liegeois F, Abela B, Pourrut X, Delaporte E, Hahn B, Peeters M; UR36, IRD and Univ of Montpellier, France
Primate lentiviruses are a diverse group that naturally infect a variety of nonhuman African primate species. So far, 6 distinct lineages (SIVcpz, SIVsm, SIVagm, SIVsyk, SIVlhoest, and SIVcol) and potential recombinant lineages have been described. In order to elucidate origins and evolution in the primate
74
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 74

Abstract not available.
75
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 75

Abstract not available.
76 High Frequency of Stereotypic Viral Escape from Dominant SIV Epitope-specific CTL in DNA-vaccinated Rhesus Monkeys.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 76
Barouch DH, Kunstman J, Glowczwskie J, Kunstman K, Egan M, Santra S, Peyerl F, Kuroda M, Schmitz J, Wolinsky SM, Letvin NL; Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA
We have previously shown that viral escape from CTL recognition resulted in AIDS vaccine failure in one vaccinated rhesus monkey infected with SHIV-89.6P. Here we show the high frequency and pattern of viral escape from immunodominant CTL responses in a cohort of DNA vaccinated rhesus monkeys following a he
77 Protection Against Pathogenic SIVmac251 Infection Elicited by Vaccination of Rhesus Macaques with a Replication Competent Ad-recombinant Priming/Subunit Boosting Regimen.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 77
Patterson LJ, Malkevitch N, Pinczewski J, Lou Y, Peng B, Kalyanaraman VS, Markham PD, Pal R, Pavlakis GN, Robey FA, Robert-Guroff M; Natl Inst of Hlth, NCI, Bethesda, MD
Replication competent Adenovirus 5 host range mutant (Ad5hr)-SIVenv/rev priming and SIV gp120 boosting has partially protected against mucosal SIV mac251 challenge. Here, the impact of multi-component SIV recombinants on protective efficacy was examined. METHODS: Rhesus macaques, 8/group, were primed intran
78 Virus-specific Immune Responses in Macaques Inoculated with Single-cycle SIV.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 78
Evans D, Bricker J, Lifson J, Lang S, Desrosiers R; New England Regional Primate Res Ctr, Southborough, MA
Novel AIDS vaccine approaches are needed that optimize safety and efficacy. We created SIV recombinants that are limited to a single cycle of infection and express 8 of the 9 viral genes. These strains are being evaluated for their ability to serve as non-replicating vaccine strains. METHODS: Single-cycle S
79 Protective Immunity in Rhesus Monkeys Immunized with Replication-defective HIV-1 Vaccine.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 79
Tung F, Cole K, Tung L, McClure H, Montelaro R; GeneCure Biotechnologies, Atlanta, GA
Live, attenuated simian immunodeficiency virus (SIV) elicited protective immunity in rhesus monkeys. This animal model provides evidence that protective immunity can be elicited by vaccination. However, this vaccine approach was hindered by safety concerns that the live attenuated HIV-1 may cause disease in
80 Enhanced Simian Immunodeficiency Virus Replication and Accelerated Progression to AIDS in Macaques Primed to Mount a CD4 But Not a CD8 T-cell Response to the Viral Envelope Protein.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 80
Staprans SI, Barry AP, Silvestri G, Safrit JT, Kozyr N, McClure H, Montefiori D, Cohen JL, Feinberg MB; Emory Univ Sch of Med, Atlanta, GA
CD4 T-cells act as both key immune effector cells as well as important targets for HIV infection. Therefore, the relative balance of CD4 versus CD8 responses induced by candidate AIDS vaccines may be an important determinant of vaccine efficacy. METHODS: To characterize a live attenuated varicella zoster vi
81 Toll-like Receptor Ligands can Modulate Dendritic Cell Functions to Augment Virus-specific T-cell Responses.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 81
Lore K, Seder RA, Khojasteh S, Betts MR, Brenchley JM, Kuruppu JC, Perfetto SP, Roederer M, Koup RA; Vaccine Res Ctr, Natl Inst of Hlth, Bethesda, MD
Abstract not available.
82 Safety, Tolerability, and CD8+ T-cell Immunogenicity of High Dose Live Recombinant Canarypox ALVAC-HIV Vaccine (vCP1452) in Healthy, HIV-1 Uninfected Adults.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 82
Goepfert P, Horton H, McElrath J, Surunathan S, Mallet L, Verdier F, Weinhold K, Allen M, Shea T, Chiu YL, Rossini T, Self S, Corey L; Univ of Alabama at Birmingham
Canarypox ALVAC-HIV vaccine (vCP1452) elicits HIV-1 specific CD8 + T-cell responses when given to healthy uninfected adults; however, only a minority of participants (ppts) has had detectable responses in prior vaccine trials. We hypothesized that increasing the dose of vCP1452 would result in a greater fre
83 Evolutionary Indicators of Vaccine Efficacy from the ALVAC Phase II Trials.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 83
Nickle DC, Davis K, Liu Y, McLaughlin S, Genowati I, Zhao H, Pathmajeyan M, Rose L, Learn GH, Sheppard HB, Celum C, Mullins JI; Univ of Washington, Seattle
The ALVAC HIV-1 vaccine, designed to stimulate production of cytotoxic T-cells (CTL), is an attenuated canarypox vector genetically altered to contain copies of HIV-1 genes (e.g., gag and env). We studied vaccinees in AVEG and HIVNET trials of ALVAC who subsequently became infected with HIV-1, in an effort
84 What Constitutes Effectiveness for an HIV Vaccine that Ameliorates Viremia: Issues Involving Surrogate Endpoints in Efficacy Trials.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 84
Gilbert P, DeGruttola V, Hudgens M, Self S, Hammer S, Corey L; Fred Hutchinson Cancer Res Ctr, Seattle, WA
Initial HIV vaccines (vxs) are unlikely to prevent acquisition of HIV in all recipients. Moreover, several current vxs are designed to reduce viremia post-acquisition of infection. Efficacy trials of such vxs will evaluate vx effects on post-acquisition endpoints, including onset of antiretroviral therapy (
85lb Replication-Defective Adenovirus Vector Vaccines Attenuate SIVmac239 and SHIV89.6P Challenge Infections: Effects of Challenge Virus, MHC Class I Expression and Multiple Vaccine Antigen Expression
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 86
J.W. Shiver*1, D.R. Casimiro1, X. Liang1, W.A. Schleif1, F. Wang1, Z. Zhang1, A. Bett1, M. Davies1, L.G. Tussey1, J.H. Condra1, T. Fu1, L. Handt1, A.B. McDermott2, D.I. Watkins2, E.A. Emini1
These studies show that Ad5 vector-containing vaccines elicit attenuating cellular immune responses against both SHIV89.6P and the stringent SIVmac239 challenge viruses. In addition, attenuation of the SHIV infection was achieved without a relevant immunodominant MHC-I allele and using a vaccine antigen that was only 85% homologous (gp140-jrfl). The attenuating effect was also greater in animals that had been immunized against multiple viral proteins.
86 Persistent Brain Injury in HIV Patients on ART.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 86
Cardenas VA, Meyerhoff DJ, Chao LL, Rothlind JC, Studholme C, Rogers LJ, Lampiris H, Chesney M, Weiner MW; Univ of California at San Francisco
Numerous studies reported CNS damage due to HIV prior to anti-retroviral therapy (ART). Antiviral medications are now in widespread use, greatly mediating the immune suppressing effects of HIV, but ART may not halt CNS damage. The goal of this project was to determine the effects of HIV on the brain of part
87 HIV-associated Neuromuscular Weakness Syndrome.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 87
Simpson D, Estanislao L, Marcus K, Truffa M, McArthur J, Lucey B, Dorfman D, Naismith R, Guerrero I, Mendez J, Lonergan T, Landau Y, Harris M, Montaner J, Clifford D; Mt Sinai Med Ctr, New York, NY
There have been reports of progressive, severe neuromuscular weakness and hyperlactatemia associated with nucleoside reverse transcriptase inhibitor antiretroviral therapy (NRTI). We performed an analysis of such cases, with focus on neurological, electrophysiological, pathological, and metabolic features.
88 Adaptation of Neurotropic Primary HIV-1 Isolates for CD4-independent Replication.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 88
Dunfee R, Gorry P, Taylor J, Kunstman K, Bell J, Wolinsky S, Gabuzda D; Dana-Farber Cancer Inst, Boston, MA
Microglia, a major target for HIV-1 in the CNS, express lower levels of CD4 and CCR5 than target cells in peripheral blood. Reduced dependency on CD4 and/or CCR5 levels may be properties of the HIV-1 Env that increase neurotropism or neurovirulence. We previously demonstrated that a brain isolate from HIV-1
89 Systemic Macrophage Infection Associated with Development of SIV Encephalitis.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 89
Bissel SJ, Wang G, Trichel AM, Murphey-Corb M, Wiley CA; Univ of Pittsburgh, PA
A fraction of SIV-infected macaques develop SIV encephalitis during the late stages of immunosuppression. Pathologically, SIV encephalitis is characterized by the presence of activated and SIV-infected macrophages. It is believed that SIV encephalitis might develop as the result of increased trafficking of
90 Clearance of HIV-1 RNA from Cerebrospinal Fluid is Most Rapid during the First Three Days of Antiretroviral Therapy in Asymptomatic Patients.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 90
Haas DW, Johnson B, Hulgan T, Nicotera J, Spearman P; Vanderbilt Univ Sch of Med, Nashville, TN
Seminal studies of kinetics of plasma HIV-1 RNA decay during initiation of antiretroviral therapy (ART) have helped define viral dynamics of HIV replication. More recent data suggests that drug potency can be predicted by quantifying maximal plasma HIV-1 RNA decay rates during the initial days of ART. We pr
91 CXCR4-mediated Signaling on Neural Progenitor Cells: Relevance to HIV-1 Associated Dementia.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 91
Peng H, Huang Y, Erichsen D, Zheng J; Univ of Nebraska Med Ctr, Omaha
CXCR4, an important co-receptor for HIV-1 infection, also plays an essential role in neuronal development. Neural progenitor cells (NPCs) have been shown to proliferate or differentiate into neurons or glia and may play important role in neuronal repair after damage by trauma or neuro-generative disorders,
92 Regionalization of Drug Resistance in Diverse Areas of the Brain in Patients with and without Dementia who Received HAART.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 92
Saksena NK, Smit TK, Tourtellotte W, Brew BJ, Morgello S; Westmead Millennium Inst, Sydney, Australia
It is commonly accepted that the brain acts as a sanctuary for HIV because of the currently prescribed antiretroviral drugs having limited access to the brain. P-glycoprotein efflux in the blood-brain barrier (BBB) is known to limit the effectiveness and dissipation of drugs into the brain, and as a consequ
93 Tracking Movement of Super-paramagnetic Iron Oxide Labeled Monocytes in Brain by High Field Magnetic Resonance Imaging: Relevance for HIV-1 Associated Dementia.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 93
Zelivyanskaya M, Nelson J, Poluektova L, Uberti M, Boska M, Gendelman H; Univ of Nebraska Med Ctr, Omaha
An unresolved question for HIV encephalitis and its associated dementia is how few infected brain mononuclear phagocytes (MP; brain macrophages and microglia) cause wide-spread neuronal damage. One hypothesis is that MP pro-inflammatory secretory products incite an amplification of inflammatory neurotoxic a
94 Impaired Nerve Regeneration in HIV-associated Neuropathy.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 94
Polydefkis MJ, Hauer P, Brown A, McArthur JM; Johns Hopkins Univ Sch of Med, Baltimore, MD
Loss of cutaneous innervation is a fundamental complication of HIV-associated sensory neuropathy (HIV-SN) that contributes to morbidity, limits antiviral therapy, and can compromise viral suppression. There is great interest in preventing or reversing the peripheral neuropathy associated with HIV infect
95 Vacuolar Myelopathy In Transgenic Mice Expressing HIV-1 Nef in Oligodendrocytes With Alteration of Oligodendrocyte Phenotype In Vitro.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 95
Kay DG, Radja F, Albrecht S, Jolicoeur P; Clin Res Inst of Montreal, Canada
We previously reported that Transgenic (Tg) mice expressing the entire HIV-1 genome, under the control of the myelin basic protein promoter (MBP/HIV Wt ), developed a vacuolar myelopathy (VM), closely resembling the human disease. METHODS: Generation of Tg mice, Southern, Northern and Western blotting, cell
96 Breast Milk Shedding of Drug-resistant Subtype C HIV-1 and Among Women Receiving Single-dose Nevirapine.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 96
Lee E, Kantor R, Johnston E, Mateta P, Zijenah L, Katzenstein D; Stanford Univ, Palo Alto, CA
Breastfeeding is a significant risk factor for HIV mother to child transmission (MTCT) with estimated transmission rates at 0.5%-2% per month. Interventions in MTCT include single-dose (SD) maternal nevirapine (NVP) and NVP prophylaxis to breastfeeding infants. Selection and shedding of NVP resistant virus
97 Late Postnatal Transmission of HIV in Breastfed Children: An Individual Patient Data Meta-analysis (The Breastfeeding and HIV International Transmission Study).
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 97
Read JS, Newell ML, Leroy V, Dabis F; Natl Inst of Hlth, Bethesda, MD
Relatively little information exists regarding either the risk or timing of breastfeeding transmission, or potential risk factors for such transmission. We analyzed individual patient (pt) data from randomized, placebo-controlled clinical trials to 1) estimate the contribution of late postnatal transmission
98 Trends in Mortality among HIV-1 and HHV-8 affected Mother-infant Pairs in Zambia.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 98
Mulindi M, Veronica M, Boris D, Sphiri P, Jubra M, Brad B, Chipepo K, Ghanapati B, Winslow K, Charles W, Charles M; Univ of Zambia, Univ Teaching Hosp, Lusaka
To determine trends in mortality among Zambian mother-infant pairs (MIP) where the mother was either dually infected with both HIV-1 and HHV-8, infected with either HHV-8 or HIV-1 alone, or not infected with either virus. METHODS: Prospective, longitudinal study of Zambian MIP classified into 4 separate coh
99 A Phase I/II Study of the Safety and Immunogenicity of an HIV-1 ALVAC Vaccine in Infants Born to HIV-infected Mothers.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 99
McFarland E, Johnson D, Fenton T, Muresan P, McNamara J, Hawkins E, Estep S, Read J, Gunurathan S, Lambert J; Univ of Colorado Hlth Sci Ctr, Denver
ALVAC-HIV vCP205 (Aventis Pasteur) is recombinant Canarypox expressing gag p55, p15 protein, gp41 anchoring region of HIV-LAI, and gp120 of HIV-1 MN. It is safe and immunogenic in adults. METHODS: PACTG 326 Part I, a randomized, placebo (PL) controlled, double-blinded study, enrolled infants in 3 groups: hi
100 Allelic Variants of MDR1 Alter Pharmacokinetics of Nelfinavir Resulting in Higher Drug Levels and More Rapid Decline in Plasma HIV-1 RNA in Children.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 100
Singh K, Saitoh A, Powell C, Fenton T, Fletcher C, Brundage R, Starr S, Spector S; Univ of California at San Diego, La Jolla
The multidrug-resistance transporter gene (MDR1) encoding for P-glycoprotein and genes encoding for isoenzymes of cytochrome P450 (CYP) have an important role in transport and metabolism of many drugs including antiretrovirals. This research examined the impact of allelic variants of MDR1 and CYP genes on n
101 Subclinical Inflammation in the Female Genital Tract is Strongly Associated with Vaginal Viral Shedding Independent of Plasma Viral Load.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 101
Lennox J, Ellerbrock T, Bush T, Conley L, Evans-Strickfaden T, Hart C; Emory Univ, Atlanta, GA
Previously, we demonstrated that plasma and vaginal viral loads are strongly correlated, and release of pro-inflammatory cytokines associated with cervical ulceration markedly enhances vaginal HIV shedding. However, vaginal viral load can increase and decrease significantly after controlling for plasma vira
102 Low Bone Mineral Density in HIV-infected Women.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 102
Jacobson D, Knox T, Shevitz A, Gorbach S; Tufts Univ Sch of Med, Boston, MA
Low Bone Mineral Density (BMD) has been associated with use of antiretroviral medications in HIV infected men. Few observational studies have evaluated the prevalence of osteopenia in women and change in BMD over time. METHODS: We collected annual measurements of total BMD by DXA scan (Hologic QDR 2000), de
103 HIV Infection and Protease Inhibitor Use are Not Associated with Reduced Bone Mineral Density in Older HIV-infected Women.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 103
Arnsten JH, Freeman R, Santoro N, Schoenbaum EE; Montefiore Med Ctr, Bronx, NY
Osteopenia is an adverse event in HIV-infected patients (pts) and a sequelae of normal aging in women. To date, no studies have described the prevalence of reduced bone mineral density (BMD) in older, peri- and post-menopausal HIV-infected women. METHODS: Using dual-energy X-ray absorptiometry, we analyzed
104 Mannose-specific Lectins as Novel Microbicides against HIV?
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 104
Schols D, Hatse S, Vermeire K, Princen K, Peumans W, Damme EV, Clercq ED, Balzarini J; Rega Inst for Med Res, Katholieke Univ Leuven, Belgium
There is an urgent need for the development of effective microbicides against HIV. Here we evaluated the activity of several mannose-specific binding lectins for their antiviral activity against HIV-1, HIV-2, and drug-resistant HIV-1 strains. METHODS: Lectins were evaluated for their antiviral activity agai
105 A Novel Microbicide that Prevents Intravaginal Transmission of SIV.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 105
Ambrose Z, Miller C, Compton L, Hildreth J, Lifson J, KewalRamani V; Natl Cancer Inst, Frederick, MD
Sexual transmission accounts for greater than 90% of worldwide HIV infection. Moreover, the incidence and prevalence of HIV infection in women has been increasing. Vaginal microbicides provide a female-controlled strategy to prevent HIV transmission. We have chosen to evaluate an HIV inactivating agent, 2-h
106 Role of Animal Studies in Vaccine Evaluation.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 106
Feinberg M; Emory Univ Sch of Med and the Emory Vaccine Res Ctr, Atlanta, GA
HIV is fundamentally different from any pathogen whose infection can now be successfully prevented by vaccination. Indeed, both the nature of the challenges to AIDS vaccine development and the strategies being pursued to overcome them are unprecedented in the history of vaccinology. METHODS: As such, tradit
107 The Role of Neutralizing Antibodies in the Prevention of HIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 107
Zolla-Pazner S; Veterans Affairs Med Ctr and New York Univ, New York
These data necessitate a new look at the V3 loop as an antigenic determinant to be included in candidate vaccine for the induction of neutralizing of broad (rather than species-specific) activity.
108 Vaccine Clinical Trials Update.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 108
Hammer S; Columbia Univ Coll of Physicians and Surgeons, New York, NY
There is no higher priority in HIV research than the development of an effective preventive HIV vaccine. Worldwide control of the pandemic is dependent on the success of this effort. METHODS: The current status of HIV vaccine candidates and the strategies for their use will be reviewed. RESULTS: The ideal H
109 New Requirements for Efficacy Trials.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 109
Self S; Univ of Washington, Seattle
Abstract Not Available.
110 DC-SIGN Function in HIV-1 Transmission.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 110
KewalRamani VN; Natl Cancer Inst at Frederick, NIH, DHHS, MD
Dendritic cells pulsed with low amounts of HIV-1 efficiently transmit the virus to primary CD4+ T-cells. Molecular insight to this process was aided through the identification of a myeloid-derived dendritic cell expressed molecule known as DC-SIGN. Through high affinity interactions with primate lentiviral
111 Cellular Defenses Against Retroviruses.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 111
Bieniasz P; Aaron Diamond AIDS Res Ctr, The Rockefeller Univ, New York, NY
Host susceptibility to retroviral infection is in part determined by genes whose products have antiviral activity. The Fv1 (Friend virus susceptibility-1) gene, which inhibits murine leukemia virus (MLV) replication in mice, is one such restriction factor. Fv1 blocks postentry, pre-integration steps of the
112 Effector T-cells and HIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 112
Unutmaz D; Vanderbilt-Ingram Cancer Ctr, Vanderbilt Univ, Nashville, TN
HIV-1 infection of primary human T-cells requires cellular activation and expression of HIV-1 receptors on the cell surface. We hypothesize that effector/ memory subsets of T-cells are preferentially targeted by R5-tropic strains of HIV-1 in vivo because of higher expression of CCR5 and their recently activ
113 Enhancement of HIV Infection by Dendritic Cells: Transfer of HIV to Target Cells Through an Infectious Synapse.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 113
McDonald D, Wu L, Bohks SM, KewalRamani VN, Unutmaz D, Hope TJ; Univ of IL, Chicago, IL
Monocyte derived dendritic cells (MDDCs) can efficiently bind and transfer HIV infectivity, through cell surface proteins such as DC-SIGN, without themselves becoming infected. Under conditions of limiting soluble virus, MDDCs greatly enhance infection of target cells. METHODS: To reveal the behavior of HIV
114 Stopping HIV Infection Before It Begins in Women.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 114
Solomon S; YRG Ctr for AIDS Res and Educ, Madras, India
Over 40% (in India about 25%) of HIV infections now occur among women, and a very high proportion of them through sex. The prevention efforts of the first 20 years of the HIV epidemic have failed to meaningfully make inroads as women continue to be vulnerable to HIV, often from economic, social, cultural, a
115 Natural History of HIV-1 Infection in Women -- Findings from the Women's Interagency HIV Study.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 115
Greenblatt RM; Univ of California, San Francisco
AIDS cases among women in the U.S. continue to increase at a rate that exceeds increases among other demographic groups. Sex dimorphism exists in the natural history (including treated natural history) of HIV infection. The Women s Interagency HIV Study (WIHS) is the largest domestic cohort study of women l
116 The Influence of Vitamin A and Hormonal Contraception on HIV Transmission and Disease Progression in Women.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 116
Baeten JM, Kreiss JK, Lavreys L, McClelland RS, Sagar M, Martin HM, Richardson BA, Chohan B, Panteleeff D, Emery S, Mandaliya K, Ndinya-Achola JO, Bwayo JJ, Overbaugh J; Univ of Washington, Seattle
Identification of modifiable factors that impact HIV-1 transmission and disease progression is needed, especially for resource-poor settings where options for treatment and prevention of HIV-1 are limited. Vitamin A deficiency and hormonal contraceptive use are common among women in developing countries, an
117 The Impact of Sex/Gender on Antiretroviral Therapy and its Complications.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 117
Squires K; Univ of Southern California, Los Angeles
Abstract Not Available.
118 Mechanisms of Action and Resistance to Entry Inhibitors
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 118
E Hunter
The development of inhibitors targeted to different steps in the HIV entry process provides a high potential for synergistic, combination therapy in the foreseeable future.
119 Pathogenic Mechanisms of HIV Disease: The Multi-faceted Effects of Virus Replication and Viremia on the Host
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 119
A S Fauci
Active virus replication has profound and multi-faceted effects on resting CD4+ T-cells, B-cells, and NK-cells in HIV-infected individuals involving aberrant gene expression, phenotypic abnormalities, and functional defects that likely play an important role in the pathogenic mechanisms of HIV disease.
120 Limited Role of Cellular Immune Responses in SIV-infected Sooty Mangabeys.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 120
Barry AP, Sumpter B, Silvestri G, Staprans SI, Feinberg MB; Emory Univ, Atlanta, GA
Naturally SIV-infected sooty mangabeys (SMs) do not develop CD4 + T-cell depletion and AIDS despite chronic high levels of virus replication, limited anti-SIV CTL responses measured ex-vivo, and a short in vivo lifespan of infected CD4 + T-cells. We proposed that CTL responses do not contribute to control o
121 Increased SIV Viremia Following In Vivo CD8+ T-lymphocyte Depletion in Sooty Mangabeys with Natural SIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 121
Wang Z, Kassis N, Staprans S, Elliott M, O'Neil S, Schmitz JE, Reimann KA, McClure HM, Johnson RP, Kaur A; New England Regional Primate Res Ctr, Southborough, MA
Sooty mangabeys naturally-infected with SIV do not develop AIDS despite evidence of cytopathic infection, high viral load, and high viral turnover rate. However, unlike pathogenic lentiviral infection, increased lymphocyte turnover is not detected, suggesting that there is decreased bystander cell lysis in
122 T-cell Subsets that Harbor HIV In Vivo: Implications in HIV Pathogenesis.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 122
Brenchley J, Ambrozak D, Hill B, Betts M, Roederer M, Douek D, Koup R; Natl Inst of Hlth, Bethesda, MD
HIV can infect non-dividing cells, but productive infection in vivo is facilitated by T-cell activation and/or proliferation. In vivo, CD4 + T-cells comprise many phenotypically and functionally distinct subsets. Infection within each of these subsets could occur with different efficiencies based upon vario
123 Systematic Analysis of Host Factors Modifying CD4+ Cell Permissiveness to HIV-1.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 123
Ciuffi A, Bleiber G, Martinez R, Suarez C, Telenti A; CHUV Lausanne, Switzerland
The genetic background of an individual has been shown to influence pathogenesis of HIV-1. Polymorphisms in several host genes implicated in the HIV life cycle help predict disease progression. We aimed at developing an in vitro model to identify polymorphisms in new gene candidates that restrict HIV-1 repl
124 Viral Kinetics of SIV mac251 in Acute Infection: Estimation of the "Basic Reproductive Ratio".
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 124
Mohri H, Mushtaq N, Bohm R, Gettie A, Ribeiro R, Perelson AS, Ho DD; Aaron Diamond AIDS Res Ctr, New York, NY
Early viral kinetics can be characterized by the basic reproductive ratio (R0), the average number of cells infected by the progeny of an infected cell when almost all cells are uninfected. For a vaccine to prevent infection, R0 has to be driven below 1. Thus, the accurate determination of R0 is important t
125lb Mechansim of CCR5 viral dominace in macaques coinfected with CXCR4- and CCR5- SHIV.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 125lb
Harouse JM, Buckner C, Gettie A, Fuller R, Bohm R, Blanchard J, Cheng-Mayer C; Aaron Diamond AIDS Reseacrh Center, The Rockefeller University, New York, New York
The underlying mechanism for R5 dominance and emergence of X4 variants late in infection remains undefined. Pathogenic chimeric envelope SHIVs that transmit, replicate and induce disease with comparable efficiencies when inoculated singly into naïve rhesus macaques, but are specific for either the CCR5 (SHI
126 Dual HIV-1 Infection Associated with Rapid Disease Progression.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 126
Gottlieb GS, Nickle DC, Jensen MA, Wong KG, Li F, Liu SL, Rademeyer C, Learn GH, Abdool Karim SS, Williamson C, Corey L, Margolick JB, Mullins JI; Univ of Washington, Seattle
Infection with more than one strain of HIV has important implications for understanding HIV transmission and for vaccine development, and has led to numerous instances of recombinant viral strains of global epidemiologic significance. However, the frequency and pathogenic consequences of dual infection (wit
127 Selective Heterosexual Transmission of Envelope-constrained, Neutralization-sensitive HIV-1.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 127
Derdeyn CA, Decker JM, Bibollet-Ruche F, Heil ML, Trask SA, Chen DT, Kasolo F, Musonda R, Hahn BH, Shaw GM, Allen S, Hunter E; Univ of Alabama at Birmingham
Heterosexual transmission of HIV-1 is generally restricted to infection by one or only a few viruses from amongst a complex quasispecies. This bottleneck has been attributed in part to preferential selection of virus utilizing CCR5 (R5) as a coreceptor. However, since R5 utilization appears to be necessary
128 HIV-infected Patients Have a Defect in B-cell-CD4+ T-cell Interactions That Is Dependent on the Presence of Viremia.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 128
Malaspina A, Moir S, Ehler L, Liu S, Mclaughlin M, Planta AM, Dybul M, Chun TW, Fauci A; Natl Inst of Allergy and Infectious Diseases, NIH, Bethesda, MD
The induction of effective humoral immune responses involves bi-directional interactions between B cells and CD4 + T-cells, the most important of which is the upregulation on activated B cells of CD80/CD86 that then stimulate CD4 + T-cells through ligation of CD28. Here we report the effect of HIV viremia o
129 Pharmacological Cellular Sanctuaries in T- and NK-cells Resistant to Protease Inhibitors.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 129
Valentin A, Poirier RH, Morrow M, Aleman K, Yarchoan R, Little R, Pavlakis GN; Natl Cancer Inst, Frederick, MD
Highly active antiretroviral treatment (HAART) fails to eradicate all the infected cells from HIV-1 infected individuals. We hypothesized that, in addition to the emergence of resistant HIV strains, therapeutic failure might be the result of suboptimal effects of drugs in infected cells due to high expressi
130 Exposure to HAART Is Associated with an Increased Risk of Myocardial Infarction: The D:A:D Study.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 130
Friis-Moller N, Weber R, D'Arminio Monforte A, El-Sadr W, Reiss P, Dabis F, Morfeldt L, Wit SD, Pradier C, Calvo G, Law M, Kirk O, Sabin C, Lundgren JD; Copenhagen HIV Programme (CHIP), Hvidovre Univ Hosp, Denmark
It remains controversial whether extended exposure to HAART leads to an accelerated risk of Myocardial Infarction (MI). METHODS: D:A:D is a prospective observational study of 23.490 patients (pts) from 11 cohorts in three continents. Years on HAART indicate time since start of either a PI or NNRTI. Enrolmen
131 Carotid Imtima-media Thickness in HIV-infected and Uninfected Adults: ACTG 5078.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 131
J. Currier1, M. Kendall2, K. Henry3, F. Torriani4, S. Storey5, C. Shikuma6, K. Mickelberg7, B. Alston8, M. Basar9, R. Zackin2, H. Hodis10
In a matched analysis that controlled for known risk factors for CHD, clinically relevant differences in baseline IMT were not demonstrated between subjects with dyslipidemia and over 2 yrs of PI exposure, subjects who arePI naïve, and HIV-uninfected controls. Longitudinal follow-up is ongoing to determine whether rates of progression of carotid IMT are influenced by PI exposure and HIV infection.
132 Increasing Incidence of Cardiovascular Disease in HIV-infected Persons in Care.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 132
R. D. Moore, J. C. Keruly, G. Lucas
Based on National Health and Nutrition Examination Survey Epidemiologic Follow-up Study, the age-sex-race population rates of CHD and CVD would be expected to be 2/1000 PY and 3/1000 PY, respectively. Compared to national CHD and CVD rates, the incidence rates of CHD and CVD in our cohort are approximately 2-3 times higher than expected. These event rates are associated not only with expected cardiovascular risk factors, but also with antiretroviral drug use.
133 Longitudinal Associations between Antiretroviral Treatments and Quantification of Tissue Mitochondrial DNA from Ambulatory Subjects with HIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 133
Cherry C, Nolan D, James I, Mallal S, McKinnon E, French M, Hammond E, Gahan M, McArthur J, Wesselingh S; Monash Univ, Melbourne, Australia
The proposed basis for NRTI-associated clinical toxicities involves cellular mitochondrial DNA (mtDNA) depletion and mitochondrial dysfunction. Critical questions remain about optimal monitoring for mitochondrial toxicity. Results are presented from two Australian sites investigating effects of antiretrovir
134 Alendronate, Vitamin D, and Calcium for theTreatment of Osteopenia/Osteoporosis Associated with HIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 134
Mondy K, Powderly WG, Claxton SA, Yarasheski KE, Stoneman JS, Hoffmann ME, Tebas P; Washington Univ, St Louis, MO
Osteopenia and osteoporosis are frequent complications of HIV infection and/or its treatment. Alendronate is the only bisphosphonate approved for the treatment of osteoporosis in men and women. We conducted a 48 wk prospective, randomized, open label study to evaluate the effects of alendronate, vit D and c
135 Effectiveness of the 23-valent Capsular Polysaccharide Pneumococcal Vaccination in HIV-1 Infected Patients Receiving Highly Active Antiretroviral Therapy.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 135
Hung CC, Chen MY, Hsieh SM, Hsiao CF, Liu WJ, Sheng WH; Natl Taiwan Univ Hosp, Taipei
Immunization with 23-valent pneumococcal polysaccharide vaccine (PPV) may increase incidence of pneumonia in HIV-1-infected patients (pts) not receiving HAART in Africa. METHODS: Pts receiving and not receiving 23-valent PPV were prospectively observed for changes of CD4 + and PVL at wk 4 of vaccination and
136 Use of Antiretroviral Therapy During Treatment of Active Tuberculosis with a Rifabutin-based Regimen.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 136
Burman W, Benator D, Vernon A, Khan A, El-Sadr W, Silva C, Lahart C, Weis S, Mangura B, King B, Weiner M, Jones B; Denver Publ Hlth and Univ of Colorado Hlth Sci Ctr
Rifabutin has been recommended for treatment of HIV-related tuberculosis (TB) because rifabutin has fewer drug interactions with antiretroviral drugs than does rifampin, thus facilitating use of highly active antiretroviral therapy (HAART). We evaluated use of HAART and its outcomes among patients (pts) enr
137 Tuberculosis Relapse and Acquired Rifamycin Resistance in HIV-1 Infected Persons Is Associated with Low CD4 Count, But Is Not More Common with Rifabutin than Rifampin.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 137
Nettles R, Mazo D, Alwood K, Gachuhi R, Maltas G, Wendel K, Cronin W, Bishai W, Sterling T; Johns Hopkins Univ Sch of Med, Baltimore, MD
Case-control studies have noted an association between HIV and acquired rifamycin resistance (ARR) in TB patients (pts); ARR has also been noted in HIV/TB pts treated with intermittent INH plus rifabutin or rifapentine in the continuation phase of therapy. However, there has not been a comparison of the ris
138 To Study the Safety and Antiretroviral Efficacy of Concomitant Use of Rifampicin and Efavirenz in Antiretroviral-naïve Tuberculosis Co-infected HIV-1 Patients in India.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 138
Patel A, Patel K, Patel J, Shah N, Patel B; Infectious Disease Clin, Ahmedabad, Gujarat, India
Objective: To study the safety and antiretroviral efficacy of concomitant use of rifampicin (RMP) and efavirenz (EFV) in antiretroviral-naïve tuberculosis (TB) co-infected HIV-1 patients (pts) in India .
139 Childhood Exposure to Simian Virus 40 (SV40)-contaminated Poliovirus Vaccine and Risk of AIDS-associated Non-Hodgkin's Lymphoma.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 139
Engels EA, Rodman L, Frisch M, Goedert JJ, Biggar RJ; Natl Cancer Inst, Rockville, MD
Persons with AIDS have increased risk for Non-Hodgkin s Lymphoma (NHL). Recent studies have reported detection of DNA sequences from SV40 in a large proportion of AIDS-associated NHLs. SV40 was present as an accidental contaminant in poliovirus vaccines used widely in the U.S. during 1955-1962. METHODS: The
139lb Increased Atherosclerotic Progression in Patients with HIV: The Role of Traditional and Immunologic Risk Factors.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 139lb
P. Hsue1, J. Lo1, A. Franklin2, A.F. Bolger1, S.G. Deeks1, D.D. Waters1
Among HIV-infected patients, carotid IMT was independently associated with classic coronary risk factors (age, LDL-C, and hypertension) and nadir CD4 count 200. These data suggest that both immunodeficiency and traditional risk factors contribute to atherosclerosis in HIV-infected individuals. Progression of IMT in the subset with 1 year followup was accelerated by tenfold compared to non-HIV infected populations, and was associated with age and duration of PI use.
140 The Potential for Cross Resistance Between S-1360, L-870810 and Other Structurally Diverse Inhibitors of HIV-1 Integrase Strand Transfer.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 140
Hazuda D; Merck Res Labs, West Point, PA
Inhibitors of the integrase strand transfer reaction have been shown to be effective inhibitors of integration and HIV-1 replication in vitro and in vivo. S-1360 and L-870810 are the first compounds in this novel class to enter into clinical studies in HIV-1 infected patients. In the presence of human serum
141 Baseline and On-treatment Susceptibility to Enfuvirtide Seen in TORO 1 and TORO 2 to 24 Weeks.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 141
Greenberg ML, Melby T, Sista P, DeMasi R, Cammack N, Salgo M, Whitcomb J, Petropoulos C, Matthews TJ; Trimeris Inc, Durham, NC,
TORO 1 and TORO 2 are randomized, open-label, controlled, multi&#8209;center, Phase III studies of patients (pts) receiving 90 mg BID of enfuvirtide (ENF, formerly T-20) by subcutaneous injection in combination with an optimized background (OB) regimen. Here we present for the first time resistance data
142
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 142

Abstract not available.
143 Effect of Amprenavir Hyper-susceptibility on the Response to APV/Ritonavir-based Therapy in ART-experienced Adults Selected by Baseline Susceptibility (ESS40006): 24-week Data.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 143
Schooley R, Haubrich R, Thompson M, Margolis D, Schneider S, Richman D, Pappa K, Yau L, Hessenthaler S, Hernandez J; Univ of Colorado, Denver
Hyper-susceptibility (HS) to HIV-1 Protease Inhibitors (PIs) has been reported by several groups. The clinical significance of this phenomenon is unclear. METHODS: ESS40006 was designed to compare 2 regimens of Amprenavir (APV)/ Ritonavir
144 Novel Drug Resistance Profiles in Non-B Subtype HIV-1 Infections.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 144
Turner D, Brenner B, Spira B, Schapiro J, Songok M, Wainberg MA; McGill AIDS Ctr, Lady Davis Inst, Jewish Gen Hosp, Montreal, Canada
Despite the expansion of HIV-1 non-B infections worldwide, there is limited information on the effects of subtype genetic diversity on virological or treatment responses. This study characterizes clade-related mutations within the reverse transcriptase (RT) and protease (PR) genes that may impact on respons
145 Are Drug-resistance Variants Transmitted with Lower Efficiency than Wild-type?
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 145
Yerly S, Jost S, Telenti A, Flepp M, Kaiser L, Chave JP, Vernazza P, Battegay M, Furrer H, Michon C, Burgisser P, Rickenbach M, Gebhardt M, Hirschel B, Perrin L; Geneva Univ Hosp Switzerland
We assessed whether HIV-1 transmission is influenced by mutations associated with drug-resistance by comparing drug-resistance profiles between recently infected (RI) individuals and potential transmitters. METHODS: From 1999-2001, sequencing of pol gene was performed in 225 consecutive Swiss RI patients (p
146 Viral and Immune Correlates of Discordant CD4/VL Responses to NNRTI-based HAART and Comparison to a Discordant Cohort Receiving Protease Inhibitor-Based HAART.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 146
Linden D, Sufka S, Ferrari G, Fiscus S, Wrin T, Gryszowka V, Exley B, Weinhold K, Hellman N, Petropoulous C, Hicks C; Duke Univ Med Ctr, Durham, NC
A discordant response to ART occurs when CD4 counts are stable or increased over time despite persistently detectable viral load (VL). For PI-based ART, this outcome is associated with CCR-5 co-receptor tropism, diminished viral replication capacity, and enhanced CD8 responses. Discordant responses to NNRTI
146lb Factors Affecting CD4 Count Slope in Patients with Stable Viral Load Following Three Class Virologic Failure: The PLATO Collaboration.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 146lb
Ledergerber B, Lundgren JD, Fusco GP, Weber R, Wit F, Castelli F, Staszewski S, Hogg R, Walker AS, Petoumenos K, d'Arminio Monforte A, Mussini C, Lampe F, Gill MJ, Phillips AN; Univ Hosp Zurich, Switzerland
Abstract not available.
147 Intracellular Phosphorylation of Zidovudine and Lamivudine in Peripheral Blood Mononuclear Cells in HIV-infected Adolescents and Young Adults on Once- vs Twice-daily Regimens.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 147
Rodman JH, Robbins BL, Martinez J, Lindsey JC, Fridland A, Rodriguez JF, Flynn PM; St Jude Children's Res Hosp, Memphis, TN
Intracellular Zidovudine (Z) and Lamivudine (L) metabolism to triphosphate (TP) in Peripheral Blood Mononuclear Cells (PBMCs) is necessary for antiviral activity, and intracellular Z-TP and L-TP persist for a substantially longer time than Z and L in plasma. The aims of this study were to 1) compare Z-TP an
148 Effect of Efavirenz on the Pharmacokinetics of Nelfinavir and M8 in Naive, HIV-infected Patients Receiving Long-term HAART Therapy.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 148
Smith PF, Robbins G, Shafer R, Wu H, Yu S, Hirsch M, Merigan T, Morse GD; Univ at Buffalo, NY
A previous report in healthy volunteers using a 7-day 750mg q8h regimen of NFV suggested that efavirenz (EFV) increases nelfinavir (NFV) exposure by 20%. We examined the effect of EFV on the pharmacokinetics (PK) of NFV and its active metabolite (M8) in naïve, HIV-infected subjects enrolled in a PK substudy
149
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 149

Abstract not available.
150 A Composite Concentration Index to Assess Antiretroviral Regimen Potency.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 150
Fletcher CV, Anderson PL, Hoody D, Bushman L; Univ of Colorado Hlth Sci Ctr, Denver
The potency of an antiretroviral regimen is a function of drug concentrations at the site of activity and concentrations of drugs necessary to inhibit replication. No framework or methods presently exist to assess the in vivo potency of an entire antiretroviral regimen or the individual contribution of all
151 Kinetics of HIV-Specific CD4+ T-cell Responses in Subjects Treated with HAART during Primary HIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 151
Kaufmann D, Bailey P, Brander C, Truong H, Strick D, Johnston M, Altfeld M, Walker B, Rosenberg E; Partners AIDS Res Ctr, Massachusetts Gen Hosp, Boston, MA
Increasing evidence suggests that HIV-specific CD4 + T-cell responses in addition to CD8 CTL are critical for effective immune control of HIV infection. However, comprehensive analyses of CD4 responses during primary HIV infection (PHI) are lacking. A better understanding of these responses and of the impac
152 High Replication Capacity is Associated with High Baseline Viral Load in Untreated Subjects with Primary HIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 152
Little SJ, Frost SD, Routy JP, Collier AC, Margolick JB, Daar ES, Koup RA, Conway B, Wang L, Wrin T, Petropoulos CJ, Hellmann NS, Richman DD, Holte S; Univ of California at San Diego
To evaluate whether drug susceptibility and viral replication capacity (RC, e.g., fitness) are associated with baseline plasma viral load levels in treatment naïve subjects with primary HIV infection. METHODS: Baseline plasma viral load (VL), drug susceptibility, RC, and pol sequence analysis were evaluated
153 Co/Super-infection in Recently HIV-1 Infected IVDUs.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 153
Perrin L, Yerly S, Jost S, Monnat M, Telenti A, Chave JP, Kaiser L, Burgisser P; Geneva Univ, Switzerland
In IVDUs recently infected with high-risk behavior, co/super-infection occurs relatively frequently and persists for at least 2 yrs.
154 Frequent Detection of Acute Primary HIV Infection in Men in Malawi: Reconsideration of Counseling and Testing Approaches.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 154
Pilcher CD, Price MA, Hoffman IF, Martinson FE, Kazembe PN, Eron JJ, Miller WC, Fiscus SA, Cohen MS; Univ of North Carolina at Chapel Hill
Acute primary HIV infection (PHI) is rarely diagnosed in sub-Saharan Africa despite high HIV incidence. METHODS: We examined the prevalence and predictors of Ab-negative PHI among Malawian men in a cross sectional study. Consecutive male attendees to Lilongwe Central Hospital STD clinic (n = 929) were enrol
155 Survival in HIV-infected Liver Transplant Recipients.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 155
Ragni M, Belle S, Im K, Neff G, Roland M, Stock P, Heaton N, Humar A, Fung J; Univ of Pittsburgh, PA
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156 GBV-C Infection Inhibits CCR5 and CXCR4 HIV Strains and Alters Chemokine and Cytokine Gene Expression in PBMC Cultures.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 156
Xiang J, George SL, Wuenschmann S, Klinzman D, Stapleton JT; Iowa City VA Med Ctr and Univ of Iowa, IA
GB Virus type C (GBV-C) HIV co-infection is associated with prolonged survival or clinical benefit in 8 clinical studies, and GBV-C HIV (R5 strain) co-infection of PBMC cultures resulted in decreased HIV replication. The mechanism by which GBV-C may slow HIV disease progression is not known. In this study w
157 GB Virus C Viremia During the Natural Course of HIV-1 Infection: Viremia at Diagnosis Does Not Predict Mortality.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 157
Bjorkman P, Flamholc L, Naucler A, Wallmark E, Widell A; Malmo Univ Hosp, Malmo, Sweden
GB virus C (GBV-C) viremia has recently been proposed to be associated with improved survival in HIV-infected subjects. We have assessed whether GBV-C status at diagnosis of HIV-1 infection can be used to predict the disease course in patients not receiving combination antiretroviral therapy, and whether lo
158 Morphine Enhances Hepatitis C Virus Replicon Expression.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 158
Li Y, Zhang T, Douglas SD, Ho WZ; Children's Hosp of Philadelphia, Univ of Pennsylvania Sch of Med, PA
Although injection drug users (IDUs) are the single largest risk factor for Hepatitis C Virus (HCV) transmission, there is little information available regarding whether substance abuse enhances HCV replication and promotes HCV disease progression. Therefore, we investigated whether morphine alters HCV mRNA
159lb Persistent GBV-C virus Type C (GBV-C) Infection is Associated with Decreased Risk of Death in HIV-seroconvertors in the Multicenter AIDS Cohort Study (MACS).
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 159lb
Williams C, Klinzman D, Yamashita T, Xiang J, Polgreen P, Rinaldo C, Liu C, Phair J, Margolick J, Zdunek D, Hess G, Stapleton J; Epidemiology, NIAID/NIH/DHHS, Bethesda, MD
GBV-C is not known to cause disease, replicates in lymphocytes, inhibits HIV replication in vitro, and has been associated with a decreased risk of death among HIV positive persons in some, but not all, studies. Previous studies based on convenience samples could not rule out bias due to unknown durations o
160 Progress in Understanding the Pathogenesis of HIV-1 Related Lipodystrophy.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 160
Capeau J; U402 Faculty of Med Saint-Antoine, Paris, France
HIV-related lipodystrophy is a complex process implying factors related to the infection, treatment, and patient. Adipocytes can differentiate from mesenchymal precursors during the whole life. METHODS: This requires the sequential expression of transcription factors under hormonal control: the main factor,
161 The Pathophysiology of HIV-1 Related Insulin Resistance and Dyslipemia.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 161
Grinspoon SK; Massachusetts Gen Hosp, Boston
Insulin resistance and dyslipidemia are seen frequently among HIV-infected patients (pts), and may increase cardiovascular risk in this population. Preliminary studies demonstrate important and novel effects of specific antiretroviral medications to decrease glucose uptake in the muscle. In addition, redist
162 Defining and Monitoring Metabolic Abnormalities -- Where are We Now?
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 162
Carr A; St Vincent's Hosp, Sydney, Australia
Metabolic complications are frequent in patients receiving antiretroviral therapy, can cause significant morbidity and even mortality, and represent some of the major chronic adverse effects that limit successful adherence to antiretroviral therapy. This review will focus on the diagnosis and monitoring of
163 New Insights in the Clinical Management of HIV-1 Associated Metabolic Complications -- Putting Guidelines into Perspective.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 163
Reiss P; Natl AIDS Therapy Evaluation Ctr, Academic Med Ctr, Univ of Amsterdam, The Netherlands
The management of metabolic complications associated with current treatment for HIV-1 infection is guided by algorithms developed for managing similar abnormalities in uninfected patients (pts), by a preliminary understanding of the pathogenic mechanisms underlying these abnormalities, only limited results
164 Immune Control and Immune Failure in HIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 164
B D Walker, T Allen, M Altfeld, X Yu, P Goulder, M Addo, R Dranert, C Brander, N Frahm, M Johnston, C Corcoran, H Trong, P Lee, E Maier, K O’Sullivan, R Eldridge, M Johnston, E Rosenberg, C Hess, A Luster
These data indicate that despite initial control of viremia, durable immune control in persons following treated acute infection is more difficult to achieve, and that larger trials will be needed to determine the potential clinical and virologic benefit of this approach. Moreover, detailed studies in persons with progressive HIV infection show that in some cases strong CTL responses persist into the later stages of illness in the ence of immune escape. These data are relevant to current efforts to develop an AIDS vaccine designed to retard disease progression rather than prevent infection, and indicate that durable maintenance of low level viremia may be difficult to achieve.
165 Shifting the Paradigm of Immunologic Control of HIV.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 165
Connors M; Natl Inst of Allergies and Infectious Diseases, NIH, Bethesda, MD
Our understanding of how HIV avoids immunologic control in most individuals remains incomplete and poses some of the greatest challenges to the rational design of effective vaccines and immunotherapies. A number of new techniques have enabled the direct measurement of quantitative and qualitative aspects of
166 Antibody Neutralization and Escape by HIV-1.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 166
Shaw GM; Howard Hughes Med Inst, Univ of Alabama at Birmingham
Neutralizing antibodies (Nab) are a principal component of an effective human immune response to many pathogens yet their biological role in HIV-1 infection is unclear. Method: Here, we utilize a sensitive, single-round viral infectivity assay together with a detailed genetic analysis of virus evolution to
167 Induction of Potent Anti-HIV Immune Responses In Vivo: Application to Immune Therapy for HIV.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 167
Weiner D; Univ of Pennsylvania Sch of Med., Philadelphia
Numerous studies reported CNS damage due to HIV prior to anti-retroviral therapy (ART). Our was to determine the effects of HIV on the brain of subjects on ART METHODS: 71 HIV+ subjects (44 (8yrs, log viral load = 8.89 (2.38, Sqrt CD4 = 18.55 ( 5.36, CDC Class: 39% A, 20% B, 14% on no medication, 25% on 1-2
168 Complete Blood Count as a Surrogate CD4 Marker for HIV Monitoring in Resource-limited Settings.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 168
Chen RY, Westfall AO, Hardin M, Vermund SH, Saag MS; Univ of Alabama at Birmingham
Obtaining CD4 + cell counts are expensive and not practical for routine monitoring in many resource-limited settings. Total lymphocyte count (TLC) has been used as a surrogate CD4 marker but with varying sensitivities and specificities. METHODS: Patients were drawn from an ongoing, observational database co
169 Knowledge, Attitudes, Beliefs, and Practices Regarding Antiretroviral Therapy in HIV-infected Adults in Soweto, South Africa.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 169
Nachega J, Lehman DA, Hlatshwayo D, Mothopeng R, Karstaedt A, Chaisson RE; Johns Hopkins Univ, Baltimore, MD
Little is known about assumptions of HIV-infected patients (pts) regarding antiretroviral therapy (ART) as potential barrier to ART adherence in resource-limited countries. METHODS: From 8/15/02 to 10/17/02, a cross-sectional study of HIV and ART knowledge, attitude, beliefs, and practices (KABP) was conduc
170 Ability to Purchase and Secure Stable Therapy are Significant Predictors of Non-adherence to Antiretroviral Therapy in Kampala, Uganda.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 170
Byakika-Tusiime J, Oyugi JH, Tumwikirize WA, Katabira ET, Mugyenyi PN, Bangsberg DR; Makerere Univ, Kampala, Uganda
Seventy-two percent (72%) of people living with HIV/AIDS are in Sub-Saharan Africa. Decreasing prices of antiretroviral therapy (ART) has expanded access to therapy in Sub-Saharan Africa. While ART adherence is closely tied to viral suppression, progression to AIDS and mortality, the level of and barriers t
171 Preliminary Outcomes of Directly-observed Treatment of Advanced HIV Disease with ARVs (DOT-HAART) in Rural Haiti.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 171
Farmer P, Leandre F, Koenig S, Nevil P, Mukherjee J, Ferrer J, Walker B, Orelus C, Smith-Fawzi M; Harvard Med Sch, Boston, MA
HIV, the leading infectious cause of adult deaths in the world today, is concentrated in extremely resource-poor settings. Beginning in late 1998, we introduced ARVs to the formulary of a clinic in rural Haiti , using serology and clinical criteria to determine access to DOT-HAART: directly observed therapy
172 The Malawian Antiretroviral Program: The First Year Experience with Triomune.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 172
M Hosseinipour*1, D Namarika2, K Magomero2, F Martinson1, S Phiri3, F Neuhann3, S Luftl2
Pts retained in the program experienced marked clinical and immunologic improvement with Triomune. Severe toxicity rates were low though the high drop-out rate limits interpretation. While advanced baseline disease and medication cost likely contribute to poor retention, operations research to identify other factors must be prioritized to advance antiretroviral therapy in Malawi.
173 Long-term Follow-up of a Cohort Patients under HAART in Senegal.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 173
Laurent C, Fatou N, Gueye N, Diakhate N, Ndir A, Gueye M, Laniece I, Awa Faye M, Toure Kane C, Liegeois F, Landman R, Mboup S, Ndoye I, Delaporte E, Salif Sow P; Inst de Recherche pour le Dev IRD, UR 36 and Univ of Montpellier, France
To study at long-term the feasibility, effectiveness, adherence, toxicity, and viral resistance of ART in one of the first cohort of patients under HAART in Africa.
174 Safety, Tolerability, and Effectiveness of Generic HAART Regimens in South India.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 174
N Kumarasamy1 , S Chaguturu2, A Mahajan2, T Yepthomi1, P Balakrishnan1, A Kalamalini1, T Flanigan3, S Solomon1, K Mayer3
In this cohort, generic based HAART was safe, well tolerated and effective at increasing CD4 count in advanced pts, comparable to the experience of proprietary HAART. Increasing access to generic HAART could be an effective means to use limited resources to provide needed treatment in areas where the epidemic continues to rapidly expand.
175 Increase in Survival in HIV-1 Infected Subjects in Matola, Mozambique, after the Introduction of Combination Therapy With Generic-manufactured Antiretrovirals: Preliminary Results from the DREAM Cohort.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 175
Gialloreti LE, Luca AD, Perno CF, Liotta G, Narciso P, Magid NA, Marazzi MC, Vella S, Palombi L; Community of Sant'Egidio, Rome, Italy
Use of CART based upon generic-manufactured antiretrovirals produced an adjusted mean reduction of 87% (95% CI 51%-99%) of death hazard as compared with no CART but same background care in HIV pts with CD4 < 200 in Mozambique. Recruitment and follow-up in the DREAM cohort are continuing.
175lb Development of Affordable, Portable CD4 Counts for Resource-Poor Settings Using Microchips.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 175lb
Rodriguez W, Mohanty M, Christodoulides N, Goodey A, Romanovicz D, Ali M, Floriano P, Walker B, McDevitt J; Partners AIDS Research Center
In resource-poor settings, HIV diagnostics are largely unavailable. Technically simple, affordable, point-of-care CD4 counts are urgently needed. We have developed a microchip-based method for measuring CD4:CD8 ratios and CD4 percentages rapidly (
176 Results of the 2NN Study: A Randomized Comparative Trial of First-line Antiretroviral Therapy with Regimens Containing Either Nevirapine Alone, Efavirenz Alone or Both Drugs Combined, Together with Stavudine and Lamivudine.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 176
van Leth F, Hassink E, Phanuphak P, Miller S, Gazzard B, Cahn P, Wood R, Squires K, Katlama C, Santos B, Robinson P, van Leeuwen R, Wit F, Lange J
Overall Rx-failure was similar among the single nNRTI arms, but was higher in the NVP+EFV arm, mainly caused by more Rx discontinuations in this arm. The incidence of clinical adverse events did not differ significantly between the single nNRTI arms. Only the incidence in liver associated laboratory AEs was significantly different between the arms, with the highest incidence in the NVP (od) arm. The virologic and immunologic efficacy was comparable among all 4 arms.
177 The NEAT Study: GW433908 Efficacy and Safety in ART-naïve Subjects, Final 48-week Analysis.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 177
Nadler J, Rodriguez-French A, Millard J, Wannamaker P; Univ of South Florida Coll of Med, Tampa, FL
GW433908 (908) is an investigational protease inhibitor (PI) offering convenient dosing and a distinct resistance profile. This open-label, randomized study in ART naïve subjects compared the efficacy and safety of 908 to nelfinavir (NFV) over 48 wks. METHODS: A total 251 (249 treated) subjects with plasma
178 The Context Study: Efficacy and Safety of GW433908/RTV in PI-experienced Subjects with Virological Failure (24 Week Results).
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 178
DeJesus E, LaMarca A, Sension M, Beltran C, Yeni P; Infectious Disease Clin, Altamonte Springs, FL
GW433908 (908) is an investigational protease inhibitor (PI) with demonstrated antiviral activity, durability, and tolerability in ART-naïve subjects. This study compared the efficacy and safety of 908/ ritonavir (RTV) when dosed either once (QD) or twice (BID) daily vs
179 Tipranavir/Ritonavir Demonstrates Potent Efficacy in Multiple Protease Inhibitor Experienced Patients: BI 1182.52.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 179
Gathe J, Kohlbrenner VM, Pierone G, Arasteh K, Rubio R, LaLonde R, Piliero P, McCallister S, Garfinkel S, Chaves R, Mukwaya GM, Dohnanyi C, Shaw S, Drees U, Mayers D; Houston, TX
Tipranavir (TPV), the first non-peptidic protease inhibitor (NPPI), has a uniquely robust resistance profile, demonstrating viral load responses against multiple protease inhibitor (PI)-resistant HIV-1 both in vitro and in clinical studies. Phase IIA studies have identified a range of doses of tipranavir/
180 Changes in AIDS, Death Rates, and Survival after AIDS in the EuroSIDA Study: 1994- 2002.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 180
Mocroft A, Ledergerber B, Katlama C, Kirk O, Reiss P, d'Arminio Monforte A, Knysz B, Dietrich M, Phillips AN, Lundgren JD; Royal Free and Univ Coll Med Sch, London, UK
After the initial decline in AIDS/death rates with the introduction of HAART, information on further changes on a population level is sparse. EuroSIDA, the observational, pan-European study of 8,551 patients (pts) has up to 8 years of follow-up and is ideally placed to document long-term trends in mortality
181 Does It Matter Where You Came From? Prognosis of Patients Starting Potent Therapy, According to Initial Response.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 181
Sterne JA, May M, Costagliola D, Pezzotti P, Ledergerber B, de Wolf F, Lundgren J, Fusco JS, Staszewski S, Raffi F, Hogg RS, Phillips AN, Gill MJ, Fatkenheuer G, Chene G; Univ of Bristol, UK
Recent data from 13 cohorts in Europe and North America (the ART Cohort Collaboration) showed that in patients (pts) starting HAART CD4 count at baseline is the dominant prognostic factor. Initial response to therapy, reflected in CD4 count and HIV-1 RNA measured some months (mos) after initiation, may also
182 The Impact of Baseline Plasma HIV RNA and Adherence on Response to Therapy and Mortality After the Initiation of HAART.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 182
Wood E, Hogg RS, Yip B, Quercia R, Harrigan PR, O'Shaughnessy MV, Montaner JS; British Columbia Ctr for Excellence in HIV/AIDS, Vancouver, Canada
After adjustment for adherence, baseline HIV RNA > 100,000 remained independently associated with mortality. We also found that adherent pts with baseline HIV RNA > 100,000 were slower to suppress and were significantly less likely to ever suppress HIV RNA than those in the lower baseline HIV RNA strata and when the entire follow-up period was considered. If these findings can be independently confirmed, they may have implications for the development of therapeutic guidelines for pts with baseline HIV RNA > 100,000 copies/mL.
183 How Hard Is HAART? Residual Viral Replication and Evolution in Lymphoid Tissue during Sustained Control of Viremia.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 183
van Lunzen J, Zollner B, Stellbrink HJ, Schneider C, Degen O, Staszewski S, Christensen S, Ruiz L, Clotet B, Tenner-Racz K, Racz P; Univ Hosp Eppendorf, Hamburg, Germany
Objective: To compare residual viral replication and evolution in lymph nodes (LN) and peripheral blood (PB) of patients (pts) with sustained control of viremia during different treatment strategies. METHODS: Analyses were performed on axillary LN biopsies and PB of 32 pts achieving sustained control of viremia (
184 Molecular Approaches to Immunogens able to Elicit Broadly Neutralizing Anti-HIV-1 Antibodies.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 184
Burton DR, Calarese DA, Dwek RA, Katinger H, Pantophlet R, Parren PW, Poignard P, Rudd PM, Saphire EO, Scanlan N, Stanfield RL, Zwick MB, Wilson IA; The Scripps Res Inst, La Jolla, CA
The design of immunogens capable of eliciting broadly neutralizing anti-HIV-1 antibodies is proving difficult. Conserved sites on the envelope (Env) trimer on the surface of virions appear to be only weakly immunogenic. However, a small panel of human monoclonal antibodies (m) that do recognize these sites
185 Blocking of gp41-Mediated Fusion by Antibodies.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 185
Weiss CD, He Y, Vassell R, de Rosny E, King L, Zaitseva M, Wingfield P, Golding H; Food and Drug Admin, Bethesda, MD
Gp120 binding to cellular receptors causes gp41 to undergo conformational changes, involving 2 heptad-repeat regions in the ectodomain of gp41that fold into a 6-helix bundle (hairpin) structure. Bundle formation facilitates virus entry in part by bringing viral and cellular membrane close together for membr
186 Attacking the Co-Receptor Binding Site on gp120.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 186
Sodroski J, Choe H, Wyatt R, Grundner C, Xiang SH, Yang X, Venturi M, Labrijn A, Poignard P, Raja A, Burton D, Kwong P, Farzan M; Dana-Farber Cancer Inst, Harvard Med Sch, Harvard Sch of Publ Hlth, Boston, MA
BACKGROUND:During human immunodeficiency virus (HIV-1) entry into target cells, the vial gp120 exterior envelope glycoprotein must sequentially interact with CD4 and one of two chemokine receptors, CCR5 or CXCR4. Because the receptor-binding sites on gp120 are conserved and accessible, they are potentially vulnerable t
187 When and What Antiretroviral Therapy to Start.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 187
Hirsch MS; Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA
Two of the most perplexing questions related to antiretroviral therapy for HIV infection are when to start and what treatment regimen to begin. It is unlikely that the question of when to start will be answered by controlled trials, and decisions will, thus, be based largely on retrospective and cohort stud
188 When to Switch Antiretroviral Therapy.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 188
Deeks SG; Univ of California, San Francisco
Many patients (pts) treated with combination antiretroviral therapy fail to achieve complete viral suppression. Ongoing viral replication in the presence of therapy leads to the accumulation of drug-resistance mutations, resulting in increased levels of viremia and a greater risk of disease progression. MET
189 What Antiretroviral Therapy To Switch To?
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 189
Yeni P; Hosp Bichat, Paris, France
Similarly to initial therapy, effective rescue therapy requires the combination of active drugs, optimal drug exposure, and favorable safety profile. These conditions must be fulfilled to reach the objective of attaining and maintaining an undetectable viral load in the plasma. Drug resistance has been repo
190 When to Interrupt Antiretroviral Therapy?
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 190
Guenthard H; Univ Hosp Zurich, Switzerland
Over recent years, interrupting potent antiretroviral combination therapy has rapidly evolved to become a major field of HIV research. This is a surprising development if one considers that introduction of combination antiretroviral therapy by far has been the most successful therapeutic intervention since
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200 HIV-1 Vif can Substitute Functionally for SIV Vif Replication in Human But Not in Rhesus Monkey Cells.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 200
Kar S, Alexander L; Yale Univ, New Haven, CT
Primate lentivirus Vif often functions in a species-specific manner. We investigated if this specificity applied to HIV-1 Vif functionality in rhesus monkey cells. METHODS: We constructed 2 SIV recombinants, which contained the HIV-1 Vif gene, and from which the SIV Vif gene was deleted. In one recombinant
201 An Alteration in HIV-1 Gag Relieves the Block at Reverse Transcription in Primate Cells.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 201
Muenk C, Kootstra NA, Lucero G, Brandt SM, Verma IM, Landau NR; Salk Inst for Biological Studies, La Jolla, CA
HIV-1 does not infect nonhuman primates and replicates poorly or not all on activated nonhuman primate lymphocytes in vitro. We analyzed the basis of the block to HIV-1 replication in nonhuman primate cells. A cellular protein, APOBEC3G/CEM15 interferes with HIV replication in viruses that lack a functional
202 Enzymatic Activity of CEM15 is Essential for its Function to Suppress the Infectivity of deltaVif Virion.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 202
Takaori-Kondo A, Shindo K, kobayashi M, Arukin A, Uchiyama T; Grad Sch of Med, Kyoto Univ, Kyoto, Japan
HIV-1 Vif protein plays a crucial role in regulating virus infectivity. Recently, a cellular factor responsible for this function, named CEM15, has been identified by subtraction cloning. The amino acid sequence of CEM15 is homologous to that of apobec-1, the cytidine deaminase that is the catalytic subunit
203 Enhanced CD4 Down-modulation Allows Efficient Replication of Late-stage HIV Strains.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 203
Lama J, Arganaraz E; Univ of California at San Diego, La Jolla
We have previously shown that CD4 inhibits HIV replication by blocking Env function. This block can be relieved by the action of Nef, Env, and Vpu, which down-modulate the viral receptor and allow the synthesis of infectious particles. Defective nef alleles have been associated with slow or nonprogression t
204 Co-receptor Dependent Stimulation of HIV-1 Replication in Primary T-cells by Nef.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 204
Lundquist CA, Zhou J, Unutmaz D, Aiken C; Vanderbilt Univ Sch of Med, Nashville, TN
The Nef protein plays a crucial role in primate lentiviral replication and pathogenesis. By studying an CXCR4-tropic viral clone containing point mutations in the nef gene, we previously demonstrated a strong correlation between CD4 down-regulation by Nef and the ability of Nef to enhance HIV-1 replication
205 Disassembly of HIV-1 Cores In Vitro Reveals an Association of Nef with the Subviral Ribonucleoprotein Complex.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 205
Forshey BM, Aiken C; Vanderbilt Univ, Nashville, TN
The HIV-1 virulence factor Nef enhances viral infectivity in single-cycle infection assays and accelerates HIV-1 replication in vitro; however, the mechanism by which Nef exerts these effects has not been determined. It has been reported that the effects of Nef are mediated early after viral entry and befor
206 The Association of HIV-1 Nef with Lipid Rafts is Functionally Important for CD4 and MHC Class I Down-modulation.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 206
Heaton MA, Ravichandran KS, Hammarskjold ML, Rekosh D; Univ of Virginia, Charlottesville
Recently described lipid rafts are enriched in signaling proteins, which target there via saturated fatty acid additions, such as myristoylation and palmitoylation. HIV-1 Nef is myristoylated and reports have suggested that a fraction of Nef localizes to rafts. METHODS: We have addressed whether Nef targeti
207 Vascular Endothelial Cells Induce Dramatically Higher Levels of HIV-1 Replication in a Nef-dependent Manner.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 207
Choi J, Walker J, Pober JS, Alexander L; Yale Univ, New Haven, CT
HIV-1 infected T-cells in the peripheral blood are in frequent contact with vascular endothelial cells (VEC) that form the lining of blood vessels. We investigated if the interaction of these cells could result in an increased level of HIV-1 replication and, if so, could Nef mediate this increase. METHODS:
208 Nef Expressed from Integrase Defective HIV-1 Down-regulates CD4 Expression.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 208
Gillim L, Klotman M; Mt Sinai Sch of Med, New York, NY
We, as well as other groups, previously demonstrated that HIV-1 extrachromosomal 2-LTR circular DNA is long-lived in primary non-dividing cells. HIV-1 extrachromosomal DNA (E-DNA) has been shown to be transcriptionally active although at much lower levels than integrated proviral DNA. With the advent of int
209 Evidence of a Novel Nef Activity Involved in nef-Mediated Thymocyte Depletion in the Thymus.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 209
D'Agostin R, Su L; Univ of North Carolina, Chapel Hill
We have previously shown that in the human thymus the HIV-1 Nef protein functions as a pathogenic determinant in the HXB/LW virus without affecting viral replication. Nef is known to have many functions including CD4 downregulation, MHC I downregulation, and alteration of several T-lymphocyte cell signaling
210 HIV-1 Nef Impairs Generation of Thymic CD4+ T-cells.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 210
Chrobak P, Simard MC, Ndolo TM, Hanna Z, Jolicoeur P; Clin Res Inst of Montreal, Canada
Loss of CD4 + T-cells is the main feature of HIV infection. Impaired thymopoiesis is believed to play a role in this loss, especially in children. We have previously reported that the CD4C/HIV Nef transgenic (Tg) mice, which express HIV Nef under the control of human CD4 regulatory elements, develop an AIDS
211 Characterization of CD4+ and CD8+ T-lymphocytes in CD4C/HIV nef Transgenic Mice: Their Presence is Dispensable for the Development of a Severe AIDS-like Disease.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 211
Chrobak P, Weng X, Priceputu E, Poudrier J, Kay DG, Hanna Z, Mak TW, Jolicoeur P; Clin Res Inst of Montreal, Canada
The mechanisms by which CD4 + and CD8 + T-lymphocytes are affected during HIV-1 infection, as well as the contribution of these cells to the development of AIDS, remain to be elucidated. We have previously reported the development of an AIDS-like disease in CD4C/HIV Transgenic (Tg) mice (wasting, early deat
212 Identification of the Domain within the Subtype C Vpu that is Responsible for Efficient Transport to the Cell Surface.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 212
Singh DK, Pacyniak E, Hout D, Stephens EB; Univ of Kansas Med Ctr, Kansas City
Vpu is a small non-structural transmembrane protein encoded by human immunodeficiency virus type 1 (HIV-1) that is synthesized off the same mRNA as the Env protein. Using a recently developed VpuEGFP reporter system, we have compared the biological properties of Vpu proteins from subtype B and C isolates of
213 Activation of the ATR-initiated DNA Damage Signaling Pathway by HIV-1 Vpr.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 213
Planelles V, Murala S, Walker J, Roshal M; Univ of Utah Sch of Med, Salt Lake City
The human immunodeficiency virus type-1 (HIV-1) encodes four accessory genes (vpr, vpu, vif, and nef) that regulate various aspects of the host cell biology. Vpr encodes a 96-amino acid protein (Vpr) that causes cell cycle arrest in G2 and apoptosis in the infected lymphocytes. Several studies have indicate
214 Glucocorticoid Receptor Modulates HIV-1 Replication Through Interaction with the Leucine Motifs in Helix I and III of Vpr.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 214
Kumar D, Mahalingam S, Wagner M, Gray B, Singh SP, Srinivasan A, Gupta P, Ayyavoo V; Univ of Pittsburgh, PA
HIV-1Vpr has been shown to transactivate HIV-1 LTR through the GRE domain via interaction with Glucocorticoid receptor (GR). Steroid receptors are known to bind proteins with signature motifs such as LxxLL sequences. Based on the observance of such motifs in HIV-1 Vpr, in this study we propose to identify t
215 HIV-1 Vpr Alters the Phophorylation of hVIP/mov34.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 215
Janket ML, Mahalingam S, Ayyavoo V; Univ of Pittsburgh, PA
Viral protein R (Vpr) of HIV is known to cause G2/M phase cell cycle arrest, coinciding with increased transcription from the HIV-LTR. The mechanism of arrest is unknown, though it is thought to be mediated by Vpr interactions with cellular proteins. hVIP/mov34, a member of the eIF3 family of transcription
216 Structure of Purified Intracellular HIV-1 Reverse Transcription Complexes.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 216
Fassati A, Nermut MV; Univ Coll of London, UK
We have investigated the structure of HIV-1 intracellular reverse transcription complexes (RTCs) by confocal and transmission electron microscopy (TEM). METHODS: Cytoplasmic extracts were prepared 3, 4, and 16 hrs post-acute infection by dounce homogenisation in hypotonic buffer without detergents. RTCs wer
217 Molecular Basis of Human Immunodeficiency Virus Type 1 Vpr-associated Cytopathicity in Human CD4+ T-cells.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 217
Bolton DL, Lenardo MJ; Natl Inst of Allergy and Infectious Diseases, NIH, Bethesda, MD
Despite continuing advances in our understanding of AIDS pathogenesis, the mechanism of CD4 + T-cell depletion in HIV-1 infected individuals remains unknown. The Vpr accessory protein of HIV-1 has been reported to cause cell death, as well as enhance transcriptional activity of the proviral long terminal re
218 Molecular Analysis of HIV-1 Induced CD4+ T-lymphocyte Cytopathicity.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 218
Sakai K, Dimas J, Lenardo MJ; Natl Inst of Allergy and Infectious Diseases, NIH, Bethesda, MD
Efforts to understand the mechanism of CD4 + T-cell depletion has led to the extensive investigation of the molecular mechanism of cell death during infection. However, the mechanism of viral cytopathicity, including viral components involved, still remains undefined due to many conflicting reports. In this
219 Small Heat Shock Proteins Antagonize HIV-1 Vpr Activities through a MAPK-independent Mechanism.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 219
Benko Z, Hou J, Liang D, Chiu K, Young PG, Taricani L, Yu M, Innis S, Reed P, DiMarzio P, Bukrinsky M, Zhao Y; Northwestern Univ, Chicago, IL
HIV-1 Vpr plays a pivotal role in viral pathogenesis and is preferentially targeted by the host immune system. Vpr displays multiple, highly conserved activities, which include cytoplasmic-nuclear shuffling, induction of cell cycle G2 arrest and cell death. Method: Through 3 independent screenings for multi
220 Modulating the HIV-1 Replication Cycle Through RNAi.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 220
Jean-Marc Jacque JM, Stevenson M; Prgm in Molecular Med, Univ of Massachusetts Med Sch, Worcester, MA, USA, 01605
RNA interference (RNAi) is the process of sequence-specific, post-transcriptional gene silencing (PTGS) in animals and plants initiated by double-stranded RNA (dsRNA) that is homologous in sequence to the silenced gene. PTGS involves the generation of 21 to 26nt dsRNA fragments, generated by ribonuclease II
221 RNA Interference of Chemokine Receptor Expression Allows for Inhibition of HIV-1 Replication.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 221
Martinez MA, Gutierrez A, Armand-Ugon M, Blanco J, Parera M, Gomez J, Clotet B, Este JA; Fundacio IrsiCaixa, Barcelona, Spain
Duplexes of 21bp-RNAs, known as short-interfering RNAs (siRNA), have been shown to inhibit gene expression by a sequence-specific RNA degradation mechanism termed RNA interference (RNAi). HIV replication may be blocked by siRNA directed to the HIV genome. The objective of our study was to evaluate the effec
222 CXCR4 Gene Silencing with Multiple Small Interfering RNAs Inhibits HIV-1 Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 222
Ji J, Erb P, Klimkait T, Wernli M; Inst Med Microbiology, Basel, Switzerland
Recently, it was found that small interfering double-stranded RNAs (siRNA) provide a powerful tool to silence a gene of interest. SiRNA duplexes targeting the rev, tat, or gag genes or genomic HIV RNA were reported to inhibit HIV-1 replication, and siRNAs targeting CD4 reduced the ability of HIV-1 to enter
223 Inhibition of CCR5 Expression Using RNA Interference Selectively Blocks Infection by R5-Tropic HIV-1.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 223
Lee MT, Cullen BR; Howard Hughes Med Inst (HHMI) and Duke Univ Med Ctr, Durham, NC
We and several other groups have recently demonstrated that RNA interference (RNAi) can be used to effectively block HIV-1 replication in culture. However, RNAi functions by inducing a highly sequence specific ribonuclease activity that is primed by an ~21 nt primer called a small interfering RNA (siRNA). W
224 Silencing Gene Expression by Short Interfering RNA Targeting NF-kB Binding Site within 5' LTR.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 224
Suzuki K, Suter S, Ward R, Cooper D, Kelleher A; Ctr for Immunology, St Vincent's Hosp, Daringhurst, Australia
Recent reports demonstrate that short interfering RNA duplexes (siRNA) targeting structural and regulatory genes of HIV act through Post Transcriptional Gene Silencing (PTGS). In plants siRNA targeting promoter regions induce transcriptional gene silencing (TGS). RNA-directed DNA methylation (RdDM) of the p
225 Sustained siRNA-mediated HIV Inhibition in Primary Macrophages.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 225
Shankar P, Song E, Lee SK, Dykxhoom DM, Novina C, Crawford K, Cerny J, Sharp PA, Lieberman J, Swamy MN; Ctr for Blood Res, Harvard Med Sch, Boston, MA
Our previous study has shown that synthetic 21-23 nucleotide siRNA duplexes suppress HIV replication in cell lines and proliferating CD4 T-cells. However, the silencing effect peaks around 96 h, but tapers off thereafter, presumably because of siRNA dilution with cell division or degradation inside the cell
226 Combination Therapies Targeting CCR5 Using RNAi, Antibody, and Ribozymes Delivered by rSV40 Vectors.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 226
Cordelier P, Morse BA Jr, Kukowski J, BouHamdan M, Pomerantz RJ, Rossi J, Strayer DS; Jefferson Med Coll, Philadelphia, PA
CCR5 chemokine receptor is important in HIV entry into susceptible cells. CCR5 deletion protects from HIV infection without negative consequences. Thus, CCR5 is an excellent target for elimination by gene therapy. Recombinant SV40 vectors (rSV40) are effective in delivering combination genetic therapies and
227 Lentiviral Vectors Interfering with CD4 Down-modulation as an Anti-HIV Approach.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 227
Groschel B, Cortes MJ, Arganaraz E, Lama J; Univ of California at San Diego, La Jolla
Physiological levels of cell-surface CD4 interfere with HIV-1 replication in T-cells by a mechanism that inhibits envelope incorporation into viral membranes. It suggests that CD4 down-modulation in HIV-1 infected cells is required for the production of infectious virus particles. Three (3) viral gene produ
228 Lentivirus Packaging and Gene Transfer Vectors.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 228
Arya SK, Cho JE, Zamani A; Natl Cancer Inst, NIH, Bethesda, MD
Packaging of viral RNA into particles is a complex process involving recognition of the packaging signal in the candidate viral RNA by the nucleocapsid protein. A non-reciprocal relationship between HIV-1 and HIV-2 cross-packaging was reported. Furthermore, HIV-2 packaging machinery reportedly failed to enc
229 The HIV-1 cPPT/CTS Fragment Mediates Efficient Transgene Expression from Lentiviral Vectors.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 229
van Griensven J, Maele BV, Clercq ED, Debyser Z; Rega Inst for Med Res, Katholieke Univ Leuven, Belgium
During HIV-1 reverse transcription, the central polypurine tract (cPPT) and the central termination sequence (CTS) are responsible for the creation of a plus strand overlap: the central DNA flap. Recently it was demonstrated that the central DNA flap of HIV-1 acts as a cis-determinant of HIV-1 nuclear impor
230 A Comprehensive Approach to Gene Therapy of HIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 230
van Lunzen J, Brandenburg G, Baum C, Egelhofer M, Kuhlcke K, Martinius H, Schult-Dietrich P, Vorpahl F, Alexandrov A, von Laer D; Univ Hosp Eppendorf, Hamburg, Germany
Abstract not available.
231 Biological Therapy of HIV/AIDS Using HIV-based Vectors Containing Anti-HIV Genetic Payloads.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 231
Dropulic B, Humeau L, Lu X, Slepushkin V, Levine B, Yu Q, Ni Y, Davis B, Carroll R, Chang Y, June C; VIRxSYS Corp, Gaithersburg, MD
Due to the adverse side-effects associated with the current class of HIV-1 antiretroviral drugs, the great propensity of HIV-1 to mutate and the lack of an effective vaccine, the search for new modalities for AIDS therapy has been of the highest priority. An attractive alternative to drug therapy is biologi
231a Inhibition of HIV Infection in CD4 T-cells by Lentiviral-mediated Delivery of anti-CCR5 siRNA is Influenced by CCR5 Expression.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 231a
Butticaz C, Ciuffi A, Munoz M, Thomas J, Iggo R, Meylan P, Telenti A; Infectious Diseases and Microbiology, CHUV, Lausanne, Switzerland
RNAi provides new opportunities for therapeutic intervention. A limitation of the technique has been the dependence on transfection for oligonucleotide or plasmid siRNA delivery. Only certain cell lines can be transfected, and efficient transfection into primary cells is virtually impossible. In contrast, r
231b Efficient Inhibition of HIV-1 Replication by RNA Interference.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 231b
Brummelkamp TR, Das AT, Vink M, Bernards R, Berkhout B; Dutch Cancer Institute, Amsterdam, the Netherlands
RNA interference provides a novel means for intracellular immunization of cells against HIV-1. Virus inhibition has recently been demonstrated in transient assays in which cells are treated with synthetic short interfering RNA (siRNA). We stably transduced a human T cell line with the pSUPER retroviral vector to expres
231c Inhibition of HIV-1 Replication by Stable Cellular Expression of tat -Specific Short Interfering RNA.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 231c
Boden D, Pusch O, Lee F, Tucker L, Shank P, Ramratnam B; Brown Medical School, Providence, RI, USA
Background. The cellular introduction of short, interfering (si) RNA leads to sequence-specific degradation of homologous RNA, a process termed RNA interference (RNAi). Here, we report that adeno-associated virus-2 (AAV-2) can be modified to genetically transfer expression cassettes encoding siRNA targeting the HIV-1 t
232 Identification of a Potent Inhibitor of HIV-1 Rev Function.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 232
Bubenik J, Cochrane A; Univ of Toronto, Canada
The objective of this study is to identify novel inhibitors of HIV-1, focusing on factors affecting viral RNA metabolism and the Rev protein. METHODS: Previously, the splicing factor sf2/ASF was shown to affect HIV-1 Rev function. To identify which region(s) of the protein was responsible for this activity,
233 DDX1, a Putative RNA Helicase, Is a Cellular Co-factor of the NIS Domain of HIV-1 REV.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 233
Fang J, Kubota S, Godbout R, Pomerantz RJ; Thomas Jefferson Univ, Philadelphia, PA
Studies on the N-terminus of HIV-1 Rev suggested that aa 1-25 may be involved in: 1) maintaining Rev s secondary or tertiary structure; 2) specific recognition and binding of Rev to RRE; and 3) Rev multimerization. Rev mutants with deletions in this region lead to Rev functional inability and altered subcel
234 High Cell Type-dependent Rate of Recombination by HIV-1 But Not By Non-diversifying Retroviruses.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 234
Levy DN, Shaw GM; Univ of Alabama at Birmingham
Extensive diversification and rapid evolution are hallmarks of HIV infection, distinguishing it from many other retroviruses which display little diversity. Recombination aids HIV diversification, confounding vaccine development and fostering the emergence of multidrug resistance. A better understanding of
235 The High Frequency of HIV-1 Recombination Leads to the Efficient Generation of Mosaic HIV-1 Genome.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 235
Zhuang J, Jetzt A, Ron Y, Preston B, Dougherty J; Univ of Med and Dentistry in New Jersey (UMDNJ), Robert Wood Johnson Med Sch, Piscataway, NJ
Fourteen (14) circulating recombinant forms (CRFs) of HIV-1 have been identified. CRFs are recombinants between different subtypes of group M that have become established in human populations. Two (2) CRFs are already playing a major role in the AIDS pandemic. Many of the CRFs display significant chimerism,
236 Identification and Characterization of a Simian Immunodeficiency Virus Reverse Transcriptase High-fidelity Mutation, V148I, Identified After Infection of a Macaque with a Low-fidelity Reverse Transcriptase-containing Virus.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 236
Diamond TL, Souroullas G, Weiss KK, Lee KY, Bambara RA, Dewhurst S, Kim B; Univ of Rochester, NY
The infidelity of lentiviral reverse transcriptases (RT) has been described as the driving force for the hypermutagenesis of lentiviral genomes. This work focuses on understanding the mechanistic and structural properties of RT that contribute to this infidelity. We previously examined changes that occurred
237 Identification of a Strong, Discrete Encapsidation Determinant in a 230 nt Segment of Feline Immunodeficiency Virus Gag Explains Preferential Encapsidation of Full-length Viral mRNA.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 237
Kemler I, Azmi I, Barraza R, Poeschla EM; Mayo Med Sch, Rochester, MN
HIV encapsidation determinants have proven more complex and dispersed than those of onco-retroviruses. METHODS: To provide comparative insight into encapsidation mechanisms, we carried out the first studies of encapsidation determinants in a non-primate lentivirus. RNAse protection assays of cellular and vi
238 Novel Integrase Determinants Required for Efficient Initiation of HIV-1 DNA Synthesis.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 238
Padow M, Lai L, Zammit K, Weiss B, Dunn D, Wu X, Kappes JC; Univ of Alabama at Birmingham
Retroviral integrase (IN) protein is required for the efficient initiation of reverse transcription. HIV-1 proviral DNA containing an HIV-2 IN coding region (SG3 IN2 ) produces virus by transfection that exhibits reduced infectivity and DNA synthesis when compared to wild type SG3. Over time in culture SG3
239 Characterization of the Subcellular Distributions of FIV and HIV-1 Integrase.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 239
Vanegas M, Llano M, Poeschla E; Mayo Med Sch, Rochester, MN
HIV-1 Integrase (IN) has been reported to localize predominantly in cell nuclei, and to play a role in nuclear import of the HIV-1 pre-integration complex. Nuclear localization signals (NLS) at several locations in IN have been reported. The subcellular localization of other lentiviral INs have not been det
240 Markedly Cell Cycle-dependent Expression Phenotypes of Class I Integrase Mutants of 2 Lentiviruses (FIV, HIV-1): Wild-type Expression Levels from Unintegrated Lentiviral Vector DNA in Non-dividing Cells.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 240
Saenz DT, Loewen N, Leske D, Good M, Holmes J, Poeschla EM; Mayo Med Sch, Rochester, MN
Tat and Nef expression can occur from un-integrated HIV-1 DNA in resting T-cells, and in some proliferating cell lines, replication of class I integrase (IN) mutant HIV-1 has recently been detected. Expression from unintegrated forms, which are prevalent in vivo, may have pathophysiological significance. ME
241 SUMO-1, Ubc9, and HIV-1 Integrase Function.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 241
Berthoux L, Gurer C, Sayah D, Han YC, Mulder L, Muesing M, Luban J; Columbia Univ, New York, NY
SUMO-1 binds covalently and reversibly to cellular or viral proteins in a reaction that resembles Ubiquitination. Unlike the latter, SUMOylation does not target proteins for degradation. SUMOylation influences the subcellular localization or activity of specific target proteins, and in some cases antagonize
242 HIV-1 DNA Content does not Correlate with Integration Frequency in Patient-derived PBMCs.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 242
Swiggard W, Yu J, McGain D, O'Doherty U; Univ of Pennsylvania, Philadelphia
In the presence or absence of effective HAART, individuals infected with HIV-1 accumulate reservoirs of latently infected resting CD4 + T-cells that prevent eradication of the virus by current medications. Prior studies of the frequency of proviruses within this cell population have relied upon either limit
243 Identification of Key Cellular Factors Essential for HIV-1 Replication that Interact with HIV-1 Integrase, Protease, and Reverse Transcriptase: Novel Targets for Anti-HIV-1 Drug Discovery.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 243
Emiliani S, Rain JC, Segeral E, Moisant F, Heveker N, Legrain P, Benarous R; Inst Cochin, Paris, France
Although many interactions between HIV-1 and cellular proteins have been reported, very few of them have been shown to impact significantly viral replication. Thus, most of the cellular proteins essential for HIV-1 life cycle still remain to be elucidated. METHODS: To identify key cellular factors essential
244 Temporal Modulation of Monocyte-Derived Macrophage Gene Expression during HIV-1 Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 244
Woelk CH, Ottones F, Royer CD, Plotkin CR, Rought SE, Lozach J, Sasik R, Corbeil J; Univ of California at San Diego, La Jolla
Measuring the global effects of HIV-1 infection of monocyte-derived-macrophages (MDMs) at the level of gene expression will help to reveal how this virus triggers innate cellular immunity and elucidate some aspects of HIV-1 pathogenesis. Method: HIV-1 (ADA strain) was used to infect MDMs, which were then ly
245 Differential Gene Expression in Chronically HIV-1 Infected Monocyte-derived Macrophages.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 245
Meehan A, Llano M, Peretz M, Raghavakaimal S, Charleton M, Poeschla E; Mayo Med Sch, Rochester, MN
Macrophages, which are key cell targets for transmitted R5 HIV-1, appear to be relatively resistant to viral killing and to produce virus chronically in vivo. Gene expression profiling in chronically HIV-1 infected macrophages may facilitate understanding of this important aspect of HIV-1 infection. METHODS
246 Towards to Depletion of Resting CD4 Cell Reservoir of HIV-1.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 246
David M. Margolis DM, Ylisastigui L, Johnson H; Univ of Texas Southwestern Med Ctr, Dallas
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 YY 1 repress the LTR by recruiting histone deacetylase 1 (HDAC1) to t
247 Reactivation of Latent HIV-1 Infection by Activating Antibodies and Recombinant Proteins Targeting Costimulatory Molecules.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 247
Kutsch O, Levy DN, Shaw GM, Benveniste EN; Univ of Alabama at Birmingham
Present attempts to achieve HIV-1 reactivation in infected patients (pts) focus on cytokine treatment ( IL-2 ), or the utilization of phorbol esters as stimulating agents, but no successful in vivo data have been published to date. An improved approach to reactivate HIV-1 could be the application of recombi
248 Analysis of Gene Expression from HIV 2-LTR Circles in Primary Human Antigen Presenting Cells.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 248
Cunningham T, Smith L, Pope M, Muesing MA; Aaron Diamond AIDS Res Ctr, Rockefeller Univ, New York, NY
When the catalytic activity of the human immunodeficiency virus integrase is compromised by small molecule inhibition or via specific point mutation in the catalytic core domain of the enzyme, unintegrated viral DNAs accumulate in the nucleus in the form of 1-LTR and 2-LTR covalently closed circles. Our pre
249 Caveolin-1 Blocks HIV-1 Expression Post-transcriptionally.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 249
Llano M, Peretz M, Vanegas M, Poeschla E; Mayo Clin Rochester, MN
We previously reported that co-expression of the raft-organizing protein Caveolin-1 (Cav) specifically blocks virion production from cells co-transfected with HIV-1 proviral DNA. The effect mapped to the central membrane-associated domain of Cav, but the affected part of the HIV-1 productive phase was not e
250 OTK18 Binds to Regulatory Elements of HIV-1 LTR and Regulates Transcriptional Activity.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 250
Horiba M, Limoges J, Buescher J, Pohlman G, Gendelman HE, Ikezu T; Ctr for Neurovirology, UNMC, Omaha, NE
OTK18 is a novel transcriptional factor isolated from HIV-1 infected human monocyte-derived macrophages (MDM) by differential display. We showed HIV-1 replication is suppressed in MDM by OTK18 through inhibition of viral long terminal repeat (LTR) promoter activity. The precise binding sites of OTK18 have n
251 Role of Structured Regions within the R-U5 Intron of Simian Immunodeficiency Virus in RNA Packaging and Dimerization.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 251
Whitney JB, Spira B, Wainberg MA; McGill AIDS Ctr, Montreal, Canada
The incorporation of retroviral RNA into nascent virions has been studied intensively; yet precise identification of cis-acting determinants that regulate RNA packaging and dimerization are still incomplete, more so in the case of SIV. Within the HIV-1 upstream leader, the R-U5 region is notable for regulat
252 Recovery of Fitness of an Attenuated Simian Immunodeficiency Virus through Compensation in Coding and Non-coding regions.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 252
Whitney JB, Spira B, Wainberg MA; McGill AIDS Ctr, Montreal, Canada
The RNA genome of simian immunodeficiency virus consists of a dimeric structure, which by analogy to HIV-1, functions through non-covalent interactions in Stem Loop 1 (SL1) of each RNA strand. Later, an extended duplex is formed between multiple regions of the two full-length genomes. The exact nature of th
253 RNA Incorporation is Critical for Retroviral Particle Stability after Release but Not for Particle Assembly.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 253
Wang SW, Aldovini A; Children's Hosp and Harvard Med Sch, MA
The nucleocapsid (NC) domain of retroviruses plays a critical role in specific viral RNA packaging and virus assembly. RNA is thought to facilitate viral particle assembly, but our results with NC mutants indicate that it plays a critical role only in particle stability. METHODS: We investigated the assembl
254 The Involvement of RNA Sequences Downstream of the Major Splice Donor Site in HIV-1 RNA Dimerization and Packaging.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 254
Russell RS, Hu J, Spira B, Wainberg MA, Liang C; McGill AIDS Ctr, Lady Davis Inst, Jewish Gen Hosp, Montreal, Canada
Two (2) copies of human immunodeficiency virus type 1 (HIV-1) RNA are incorporated into each virus particle and are further converted to a stable dimer as the virus particle matures. Several RNA segments that flank the 5 splice donor site have been shown to act as packaging signals. Among these, stem-loop 1
255 RNA:RNA Junctions in Dimeric RNAs Isolated from Immature and Mature Murine Leukemia Virus Particles.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 255
Hibbert C, Mirro J, Rein A; Natl Cancer Inst, Frederick, MD
The retrovirus genome is a dimer of 2 identical positive-strand RNAs. These RNA dimers from mature (protease active) and immature (protease inactive) virus, have different RNA conformations. The most stable junction in mature dimers, termed the Dimer Linkage Site (DLS), is near the 5 -termini. The location
255b Molecular Characterization, Reactivation and Depletion of Latent HIV.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 255b
Hamer DH, Brooks DG, Arlen PA, Gao L, Bristol G, Berger EA, Zack JA; NCI, Bethesda, MD
A serious problem facing HIV infected patients is the inability of antiretroviral therapy to completely eliminate infection. Rebound of viral load following the cessation of therapy has been attributed largely to the persistence of a long-lived population of latently infected T cells. The scarcity of latent
256 Cholesterol Depletion of HIV-1 and SIV with Beta-cyclodextrin Inactivates and Permeabilizes the Virions: Evidence for Virion-associated Lipid Rafts.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 256
Graham DR, Chertova E, Hilburn JM, Arthur LO, Hildreth JE; Johns Hopkins Univ Sch of Med, Baltimore, MD
Recent evidence suggests HIV-1 particles assemble and bud selectively through areas in the plasma membrane of cells that are highly enriched with GPI-anchored proteins and cholesterol, called lipid rafts. Since cholesterol is required to maintain lipid raft structure and function, we hypothesized that compo
257 Heavy Rafts: A New Class of Rafts and Its Possible Role in HIV Assembly.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 257
Hammache D, Alais S, Louwagie M, Garin J, Gerlier D; Ctr Natl de la Res Sci UMR 5537, Nice, France
Assembly of several enveloped viruses, including HIV, occurs within membrane regions rich in glycosphingolipids and cholesterol called membrane rafts. Rafts can be isolated by flotation on a sucrose gradient, as low-density, Triton X-100 insoluble membrane. We recently observed that some membrane-like mater
258 HIV Pr55Gag Maturation in Membrane Rafts.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 258
Alais S, Chazal N, Gerlier D; UMR5537 CNRS-UCBL, Lyon, France
Membrane rafts are cholesterol-enriched microdomains originally characterized by their insolubility at 4°C in non-ionic detergent as Triton x-100. Rafts incorporate specific proteins such GPI-anchored proteins. They are involved in several intracellular sorting and signal transduction events. Before viru
259 In Vitro HIV-1 Infection Increases Intracellular Cholesterol.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 259
van 't Wout AB, Cunningham DM, He H, Geiss GK, Mullins JI; Univ of Washington, Seattle
Recent studies by several laboratories have highlighted the importance of cholesterol in the HIV-1 life cycle. Removing cholesterol from virions or inhibition of cholesterol biosynthesis with lovastatin inhibits HIV-1 production in vitro. This inhibition is thought to be mediated through the cholesterol-ric
260 Evidence of Intracellular Gag-Gag Interactions by Fluorescence Resonance Energy Transfer.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 260
Derdowski A, Spearman P; Vanderbilt Univ Med Ctr, Nashville, TN
Gag multimerization is both necessary and sufficient for retroviral particle assembly and release. Although interactions between Gag molecules have been shown using a variety of techniques, the initial site of these interactions remains unknown. We hypothesize that initial Gag-Gag interactions occur at a sp
261 HIV-1 Virus Particles Contain Over 4,000 Copies of the Gag Protein.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 261
Johnson MC, Briggs JA, Fuller SD, Simon M, Vogt VM; Cornell Univ, Ithaca, NY
The retroviral structural protein, Gag, is necessary and sufficient for the formation of immature retroviral particles. For Rous Sarcoma Virus (RSV) and Mason Pfiser Monkey (MPMV) the number of Gag proteins per virus particle has been determined and is approximately 1,500 and 1,900-2,100, respectively. Alth
261b PML and the Proteasome as Mediators of Intracellular Antiretroviral Innate Immunity.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 26lb
Turelli P, Trono D; Univ of Geneva, Geneva, Switzerland
Mammalian cells have evolved mechanisms that limit their susceptibility to viral infections. We previously demonstrated that the nuclear protein PML interferes with the immediate early steps of HIV replication. Here, we asked whether this phenomenon represents a general protection of human cells against ret
262 Human Vps28 is Essential for HIV-1 Virus Release.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 262
Liu B, Okumura A, Yu Y, Li L, Cohen SN, Yu XF; Johns Hopkins Univ, Baltimore, MD
HIV-1 release requires functional interaction between the L domain p6 and the host protein TSG101. Other cellular proteins in the vacuolar protein sorting pathway are also likely involved in HIV-1 release. However, the contribution of other host proteins in the process of HIV-1 budding remains to be defined
263 Characterization of Endocytic Proteins Involved in HIV-1 Budding.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 263
Oztan A, Weisz OA, Stolz D, Watkins SC, Traub L, Montelaro RC; Univ of Pittsburgh, PA
Retroviral budding mechanistically resembles both endocytic vesicle formation at the plasma membrane and intracellular vesicle formation in late endosomes. Recent studies from our lab and others have indicated a critical link between retroviral budding and various components of these two processes. Based on
264 Evidence for a Cyclophilin-Dependent Host Factor in HIV-1 Infectivity.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 264
Saphire A, Bobardt M, Gallay P; Scripps Res Inst, La Jolla, CA
We previously demonstrated that cyclophilin A (CypA) plays a role in at least 2 distinct stages in HIV-1 replication: entry and post-entry. Method: In order to examine the post-entry activity of CypA in HIV-1 infection, we employed an in trans Vpr-fusion system to introduce mutant forms of CypA into the vir
265 HIV-1 Gag Alters Actin Polymerization and Increases T-cell Chemotaxis.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 265
Ibarrondo FJ, Krogstad P, Geng YZ, Baldwin G; David Geffen Sch of Med at UCLA, Los Angeles, CA
The HIV-1 Gag protein interacts with filamentous actin in vitro and in vivo, but the significance has remained elusive. Based on prior studies involving human and nonhuman cell types, we hypothesized that these interactions might alter the turnover of the actin cytoskeleton of lymphocytes, leading to enhanc
266 HIV-1 Matrix Protein Interaction with Ezrin Containing Structures: Possible Intermediates in the Assembly Process.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 266
Gomez C, Hope T; Univ of Illinois at Chicago
Human immunodeficiency virus assembly is a highly dynamic multi-step process. Several groups have shown that matrix protein is a key player in assembly. Matrix is responsible for targeting the Gag polyprotein to the plasma membrane and for the incorporation of the viral envelope glycoproteins into budding v
267 HIV-1 and SIV p6gag is Tolerant to Small In-frame Deletions Downstream of the Late Domain.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 267
Pikora C, Wittish C, Desrosiers RC; New England Regional Primate Res Ctr, Southborough, MA
Short, unique, persistent, in-frame deletions have been previously detected within p6gag sequences obtained from 3 HIV-1-infected long-term nonprogressors (LTNPs). These deleted residues are not known to be involved in late domain activity of p6gag or in vpr binding. METHODS: Using PCR mutagenesis, we creat
268 Dissecting the Blocks to HIV-1 Particle Production in Rodent Cells.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 268
Hatziioannou T, Martin-Serrano J, Cowan S, Bieniasz PD; Aaron Diamond AIDS Res Ctr, Rockefeller Univ, New York, NY
We and others have previously shown that most rodent cells lack a factor(s) critical for the production of HIV-1 virions. Rodent cells expressing HIV-1 receptors and a cyclin T1 that supports Tat function are able to support reverse transcription, integration, and early gene expression at levels comparable
269 TSG101, Endosomal Sorting, and HIV Budding.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 269
Demirov D, Goila R, Ono A, Freed E; Natl Inst of Hlth, Bethesda, MD
Retrovirus budding is greatly stimulated by the presence of Gag sequences known as late or L domains. The L domain of HIV-1 maps to a highly conserved Pro-Thr-Ala-Pro (PTAP) sequence in the p6 domain of Gag. We and others recently observed that the p6 PTAP motif interacts with the cellular endosomal sorting
270 Syndecans on the Vascular Endothelium Serve as a Major in trans Viral Reservoir for HIV.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 270
Bobardt M, Saphire A, Gallay P; Scripps Res Inst, La Jolla, CA
We obtained several lines of evidence which suggest that a class of cell surface transmembrane proteoglycans-the syndecans-serve as in trans receptors for HIV. Specifically, syndecans by capturing HIV via their heparan sulfate chains promote HIV attachment to nonpermissive CD4-negative cells. Although they
271 Use of CCR5/CXCR4 Chimeric Receptors Reveal Evolution of HIV-1 R5 Phenotype in Relation to Pathogenesis.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 271
Fenyo EM, Karlsson I, Antonsson L, Shi Y, Karlsson A, Albert J, Olde B, Owman C; Lund Univ, Lund, Sweden
Co-receptor use of HIV-1 may influence the type of cells infected and the signal pathways activated. To understand the linkage between co-receptor use and the severity of the pathogenic process following HIV-1 infection, we tested 278 HIV-1 isolates from 23 individuals with varying severity of HIV-1 infecti
272 Evolution of R5 and X4 Human Immunodeficiency Virus Type 1 Gag Sequences in Vivo: Evidence for Recombination.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 272
Schuitemaker H, Visser J, van Rij R; Sanquin Res and Academic Med Ctr, Amsterdam, The Netherlands
HIV-1 infection is generally established by CCR5-using (R5) viruses, which persist throughout the course of infection. R5 HIV-1 variants evolve into CXCR4-using (X4) HIV-1 variants in approximately half of the infected individuals. We have previously observed an ongoing genetic evolution with a continuous d
273 A Subset of HIV and SIVs that Use an Alternative Coreceptor to Infect Primary Human Cell Cultures.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 273
Willey S, Reeves J, McKnight A, Bell J, Hudson R, Luzuriaga K, Clapham P; Univ of Massachusetts Med Sch, Worcester
The chemokine receptors CCR5 and CXCR4 are major coreceptors for HIV-1 in vivo. At least 12 other chemokine receptors or related molecules support infection of CD4 + cell lines by various HIV-1 strains. However, there is little current evidence to indicate that these alternative co-receptors contribute sign
274 Role of N-linked Glycosylation of CXCR4 in SDF-1 Binding and HIV-1 Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 274
Wang J, Babcock GJ, Choe H, Farzan M, Sodroski J, Gabuzda D; Dana-Farber Cancer Inst, Boston, MA
CXCR4 is a primary co-receptor for HIV-1, and also plays critical roles in immune responses and development. To better understand structural determinants of CXCR4 that play an important role in HIV-1 pathogenesis, we investigated cell-type dependent modifications of CXCR4 and their effects on SDF-1 and gp12
275 Generation of HIV-1 Co-receptor Switch Variants In Vitro.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 275
Pastore C, Ramos A, Mosier DE; Scripps Res Inst, La Jolla, CA
Antiviral agents that target HIV co-receptors have selected for co-receptor switch mutants in some studies but not others. The conflicting studies have used different HIV-1 isolates, co-receptor inhibitors that differ in mode of action, and distinct methods of HIV propagation. Our goal was to compare the fr
276 Isolation of a CD4-independent HIV-1 Variant with Novel Phenotypes Including Ability to Infect a Wide Range of CD4- Cells.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 276
Zerhouni B, Traven A, Saha K; Children's Hosp, Columbus, OH
Although HIV primarily infect CD4 + cells using CD4 receptors, it is well established that other CD4 - cells in the body can also be infected by HIV. Primary HIV-2 and SIV as well as laboratory strains of HIV-1 have been isolated that can enter CD4 - cells using different pathways. We have recently isolated
277 An Unusual Block in X4-Tropic HIV-1 Challenge of Mouse T-cells.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 277
Baumann J, Ahn G, Unutmaz D, KewalRamani V; Natl Cancer Inst at Frederick, MD
Expression of murine or human CXCR4 with human CD4 renders mouse fibroblasts susceptible to transduction by X4-tropic HIV-1. In contrast, murine T-cells expressing the same factors are refractory to infection by X4-tropic HIV-1. No such infection block is observed for R5-tropic HIV-1 isolates in murine T-ce
278 Single-cell Analysis of HIV-1 Infected Primary Human Macrophages.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 278
Brown A, Kawano T, Cheng-Mayer C; Aaron Diamond AIDS Res Ctr, New York, NY
Monocyte/macrophages play an important role in the transmission of HIV-1 across mucosal surfaces and in the dissemination of virus in lymphoid tissues, and they serve as a latent and/or persistently infected reservoir. Currently available molecular tools to better understand the physiological impact of HIV-
279 R5 but Not X4 Primary Viral Isolates of HIV-1 Can Localize Their cDNA to the Nucleus in Monocyte Derived Macrophages.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 279
Choi JW, Teo IA, Shaunak S; Imperial Coll, London, UK
Monotropic HIV-1.R5 isolates can productively infect monocyte derived macrophages. However, this seems to occur sporadically when monotropic HIV-1.X4 isolates are used. Therefore, we have used several monotropic X4 isolates to determine whether they can productively infect monocyte derived macrophages as me
280 Influence of V3 Charge in Conjunction with gp120 N-linked Glycosylation Patterns on Chemokine and Neutralizing Antibody Inhibition of HIV-1.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 280
Nabatov A, Pollakis G, Linnemann T, Kliphuis A, Chalaby M, Paxton W; Univ of Amsterdam, The Netherlands
The HIV-1 gp120 envelope N-linked glycosylation pattern, in conjunction with V3 charge, has been shown to modify viral co-receptor usage. We wished to identify what influence these envelope characteristics and their combinations had on virus sensitivity to inhibition with CC/CXC-chemokines, dextran sulphate
281 A Quantitative Assay to Measure Cell-to-Cell Fusion Mediated by HIV-1 Env Glycoprotein.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 281
Ataman-Onal Y, Durand PY, Reynard F, Bedin F, Altmeyer R, Girard M, Verrier B; UMR2142 CNRS-bioMerieux, Lyon, France
HIV1-target cell fusion requires the Env protein to bind CD4 and a chemokine coreceptor on the cell surface. Infected cells expressing Env can initiate syncytium formation through cell-to-cell fusion, a process that contributes significantly to the spread of HIV-1 infection and AIDS pathogenesis. Methods to
282 Removal of Glycosylation Sites within Env Proximal to the Rim of the CD4 Binding Pocket Changes Env Affinity for Soluble CD4.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 282
Pikora C, Wittish C, Desrosiers RC; New England Regional Primate Res Ctr, Southborough, MA
Neutralizing antibody responses contribute significantly to the containment of many viral illnesses. Although HIV infected individuals generate high titers of anti-env antibodies, neutralizing titers remain weak and appear late after seroconversion. Extensive glycosylation of SIV and HIV env is thought to p
283 Are Broadly Neutralizing Epitopes Exposed Differently on the HIV-1 Envelope Glycoproteins at Different Stages of Infection?
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 283
Dacheux L, Ataman Y, Verrier B, Barin F; Univ Francois Rabelais, Tours, France
According to a commonly held hypothesis, HIV viruses present early in the infection course may mask important neutralizing epitopes of their envelope glycoproteins. In contrast, viruses present at late stages of infection may be better recognized by neutralizing antibodies. The aim of our studies is to eval
284 HIV-1 Fusion Inhibitors Bind to the N-Helical Coiled-coil Domain in Receptor-activated gp41.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 284
Kilgore N, Salzwedel K, Reddick M, Allaway G, Wild C; Panacos Pharm, Gaithersburg, MD
While it has been established that peptides modeling the C-helical region of HIV-1 gp41 are potent in vivo inhibitors of virus replication a number of questions concerning their mechanism of action, including their specific molecular target, remain unanswered. It has been proposed, but never directly demons
285
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 285

Abstract not available.
286 Effect of PRA1 Suppression on SIV Virion Release, Infectivity, and Envelope Content.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 286
Blancou P, Evans DT, Desrosiers RC; Harvard Univ, Southborough, MA
Prenylated Rab acceptor (PRA1) was identified as a potential cellular binding partner of the SIV gp41 cytoplasmic domain (gp41CD) in a 2 yeast hybrid screen of a human, phytohemagglutinin-activated T-cell cDNA library. This interaction was confirmed by mammalian 2-hybrid assays. PRA1 is a 21kDa protein that
287 PI3-Kinase Regulates HIV-1 Replication Following Viral Entry in Primary CD4+ T-lymphocytes.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 287
Francois F, Klotman ME; Mt Sinai Sch of Med, New York, NY
Previously, we have shown that HIV-1 gp120 activates the PI3-kinase pathway and that basal and induced PI3-K activity is required for HIV-1 replication within primary CD4 + T-cells and macrophages. Here, we determine the stage of HIV replication at which PI3-kinase activity is required for infection. METHOD
288 Signaling Response to Cyclophilin A and Stimulation of HIV-1 Infection are Independent Functions of CD147.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 288
Bukrinsky M, Pushkarsky T, Yurchenko V, Sherry B, Brichacek B; George Washington Univ Med Ctr, Washington, DC
Cyclophilin A (CypA) is a ubiquitously distributed intracellular protein possessing peptidyl-prolyl cis-trans isomerase activity. In addition to its intracellular functions, CypA can be secreted into the extracellular environment and has been shown to induce chemotaxis of monocytes, neutrophils, and T lymph
289 HIV-1 Enters Primary Human Fetal Brain Microvascular Endothelial Cells by a Lipid Raft-independent Mechanism.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 289
Argyris EG, Acheampong E, Mukhtar M, Williams KJ, Pomerantz RJ; Thomas Jefferson Univ, Philadelphia, PA
Recent studies have demonstrated the significance of membrane cholesterol and lipid rafts in HIV-1 entry into permissive cells, including primary human brain microvascular endothelial cells (BMVECs) from adults. In this study, we examined the role of cellular cholesterol and lipid rafts in HIV-1 entry into
290 Sigma-2 Receptor Agonists Inhibit HIV Infection of Lymphocytes by Reducing Membrane Sphingomyelin Content.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 290
Crawford KW, Liao Z, Hildreth JE, Bowen WD; Howard Univ Sch of Pharmacy, Washington, DC
HIV infection of CD4 + lymphocytes and release of virions occurs in lipid rafts; cholesterol- and sphingolipid-rich microdomains of the plasma membrane. We have shown that reducing membrane cholesterol content also reduces HIV infectivity of lymphocytes and diminishes virulence of the virions released. Redu
291 Massive Transfer of HIV Particles to Non-permissive Cells during Cell-to-Cell Contacts.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 291
Blanco J, Barretina J, Clotet B, Este JA; Fundacio IrsiCaixa, Hosp Univ Germans Trias i Pujol, Barcelona, Spain
Cell-to-cell virus transmission is one of the mechanisms of viral spread and involves the transfer of HIV particles from infected to permissive cells in the absence of effective cell-to-cell fusion. Here, we describe a similar process, in which HIV can be passively transferred to resting or even nonpermissi
292 HIV-1 Mediated Signal Transduction through CCR5 Allows Infection of Resting Memory T-cells.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 292
Matthews A, Vasudevan J, Camerini D; Univ of Virginia, Charlottesville
Following transmission of HIV-1, the predominant viral quasi-species are those that enter cells exclusively via CCR5 (R5 HIV-1). As disease progresses, in approximately 50% of patients (pts) the viral entry pathway switches to a dual tropic or CXCR4 tropic nature (R5X4 or X4). This switch is rarely seen dur
293 Physical Determinants of HIV Infectivity In Vitro: Brownian Motion Underlies Target Cell Limitation.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 293
Strain MC, Levine H, Sheeter D, Ignacio CC, Havlir DV, Richman DD, Wong JK; Univ of California at San Diego, La Jolla
The infectivity of virus in vitro is typically expressed as infectious titer or multiplicity of infection. However, Brownian motion and virus lability may modulate infectivity, making these quantities highly dependent on experimental conditions. METHODS: The process of HIV infection in suspension cell cultu
294 Antibody to LFA-1 Blocks HIV-1 Infection in Primary Cells through the Activation of Caspase 8.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 294
Cimakasky LM, Hildreth JE; Johns Hopkins Univ Sch of Med, Baltimore, MD
We have shown that an anti-LFA-1 monoclonal antibody (MAb) blocks HIV-1 infection of primary cells through a post-entry mechanism. Investigation of the mechanism by which anti-LFA-1 MAb blocks infection suggested that apoptosis may be involved. We hypothesized that caspase-dependent apoptosis is induced by
295 The Infectivity and Cytopathicity of HIV-1 is Greatly Affected by the Purification State of the Virus.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 295
Schweighardt B, Heymann J, Grace E, Nixon D; Gladstone Inst of Virology and Immunology, San Francisco, CA
Standard HIV-1 stocks have been shown to contain cell-derived microvesicles and secreted HIV proteins. HIV virions can be isolated away from these contaminants using a velocity gradient method of purification. We investigated whether the contaminating factors in standard viral preparations influence the inf
295a Single Mutation in the N-terminal alpha Helix of SIV Gp41 Expands Coreceptor Usage of Viral Envelope.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 295a
Kodama T, Jin S, Murphey-Corb M; Univ of Pittsburgh, Pittsburgh, PA
Interaction of HIV-1 and SIV gp120 with CD4 induces conformational change in gp41 leading to virus-cell membrane fusion. This fusion-active gp41 conformation constitutes a six-helix bundle in which three N-terminal helices form coiled-coil internal structure that is surrounded by three C-terminal helices in
296 Cross-Clade CD4+ T-cell Recognition of HIV-1 Gag Protein.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 296
Norris PJ, Moffett HF, Cosimi LA, Kaufmann DE, Walker BD, Rosenberg ES; Massachusetts Gen Hosp, Boston
Sequence variation within the HIV-1 genome represents a significant obstacle to the development of a successful vaccine. HIV-1 viruses have been divided into different clades based on the predominant sequence present in different regions of the world. Clade B virus is found primarily in North America and Eu
297 Persistent Low Viral Load is Associated with Enhanced Th1 Responses to HIV-p24 Compared to Full Viral Suppression or Viral Failure Under Antiviral Therapy.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 297
Samri A, Costagliola D, Alatrakchi N, Marcelin AG, Biligui A, Agher R, Astriti M, Calvez V, Autran B, Katlama C, Duvivier C; Cell Immunology, INSERM U543
The aim of the study was to evaluate whether a stable low level HIV replication in patients (pts) treated with antiviral therapy can 1) allow persistence of a stronger immunity to HIV; and 2) be deleterious for the host s immune defenses against other pathogens compared to pts with controlled viremia or vir
298 HIV Replication is Associated with High Frequencies of HIV-Specific IFN-gamma+ CD4+ T-cells with Limited In Vitro Proliferation in Chronically-infected Children.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 298
Scott Z, Beaumier C, Sharkey M, Stevenson M, Luzuriaga K; Univ of Massachusetts Med Sch, Worcester
The ability of HIV-1 chronically-infected children to generate functional virus-specific CD4 + T-cell responses is poorly understood. The present study investigated the relationship between HIV-1 replication and virus (HIV-1, CMV )-specific CD4 + T-cell frequency and function in a large cohort of
299 Robust Gag-specific T-helper Response Associated with Viral Control in Pediatric HIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 299
Feeney ME, Day CL, Roosevelt KA, McIntosh K, Burchett S, Mao C, Goulder PJ, Walker BD; Partners AIDS Res Ctr, Massachusetts Gen Hosp, Boston, MA
Adults with long-term nonprogressive HIV infection frequently possess strong HIV-specific T-helper responses. A robust proliferative response to p24 antigen has been shown to correlate with low viral load in HIV-infected adults, but strong responses are seldom detected in those with progressive infection an
300
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 300

Abstract not available.
301 Proliferative Capacities and Immunocompetence of CD4+ T-cells of Normal and HIV-infected Subjects Upon TCR Stimulation.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 301
Wong JT, Ablikim M, Wang Z, Liu Z; Harvard Med Sch and Mass Gen Hosp, MA
Effective amplification of the response of CD4 + T-cells depends on both the proliferative capacities of the CD4 + T-cells upon antigen stimulation and the immunologic functions of the proliferating cells through the different stages of proliferation. METHODS: Proliferative capacities of the peripheral bloo
302 Tb4 is an HIV-1 Inhibitory Factor in Transformed CD8+ Cell Supernatants.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 302
Klotman ME, Mosoian A, Teixeira A, Chang T, High AA, Hunt DF, Shabanowitz J; Mt Sinai Sch of Med, New York, NY
CD8 + lymphocytes from normal and human immunodeficiency virus type 1 (HIV-1) infected patients (pts) produce a number of soluble factors that suppress the replication of HIV-1. Several of these factors have been identified as members of the b-chemokine family and shown to inhibit viral entry. There are oth
303 CD8+ T-cell Responses to Variable Proteins Dominate in Early HIV-1 Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 303
Bansal A, Sabbaj S, Gough E, Ritter D, Perkins C, Tang J, Korber B, Kaslow R, Wilson C, Mulligan M, Aldrovandi G, Kilby M, Goepfert P; Univ of Alabama at Birmingham
CTL escape has been demonstrated numerous times, yet it is not clear which epitopes are protective and to what extent escape mutations play a role in host pathogenesis. We hypothesized that responses maintained during chronic infection are directed against more conserved proteins than are responses observed
304 Heightened HIV-1 Replication in Lymphoid Follicles May Be Due to Immune Privilege.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 304
Folkvord J, Connick E; Univ of Colorado Hlth Sci Ctr, Denver
To evaluate the hypothesis that follicular regions of lymphoid tissue are immune privileged sites, HIV-producing cells and antiretroviral effector protein expression were quantified in follicular (F) and extra-follicular (EF) regions of inguinal lymph nodes (LN) from 15 untreated HIV-infected individuals. M
305 Dynamics of Virus-specific CD8+ T-cell Immunity and Viral Escape during Acute and Chronic HIV-1 Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 305
Cao J, McNevin J, Liu Y, Zhao H, Genowati I, Mullins JI, McElrath MJ; Fred Hutchinson Cancer Res Ctr, Seattle, WA
Virus-specific CD8 + T-cells largely mediate control of HIV-1 replication during acute and chronic infection. HIV-1 can override the immune pressure by mutation of the CD8 + T-cell epitope sequences so that specific CD8 + T-cells no longer recognize the infected cells. Method: To determine the interaction b
306 Simultaneous Assessment of Degranulation and Cytokine Production in HIV- and CMV-specific CD8+ T-cells Ex Vivo.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 306
Betts M, Brenchley J, Ambrozak D, Price D, Douek D, Roederer M, Koup R; Vaccine Res Ctr, NIAID, NIH, Bethesda, MD
After recognition of cognate peptide, various effector functions are elicited in CD8 + T-cells, including cytokine production and cytotoxicity. It has been proposed that HIV-specific CD8 + T-cells are impaired in their cytotoxic capacity; however, HIV-specific CD8 + T-cells are clearly cytotoxic directly ex
307 HIV-1 Superinfection Despite Broad CD8+ T-cell Responses Containing Replication of the Primary Virus.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 307
Allen TM, Altfeld M, Yu XG, Johnston MN, Agrawal D, Korber BT, Montefiori DC, O'Connor DH, Davis BT, Lee PK, Maier EL, Goulder PJ, Brander C, Rosenberg ES, Walker BD; Massachusetts Gen Hosp and Partners AIDS Res Ctr, Boston
Increasing evidence suggests that virus-specific CD8 + T-cell responses are important in the control of HIV-1 replication. Early treatment of persons with acute HIV-1 infection followed by supervised treatment interruptions (STI) has shown promise for augmenting HIV-1-specific immunity and enhancing immune
308 Immune Selection by CTL is an Important Factor for Sequence Variation in HIV-1 Nef.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 308
Harrer T, Goldwich A, Schmitt M, Bauerle M, Bergmann S, Hamacher M, Kalden JR, Muller R, Kasten S, Harrer T; Univ of Erlangen, Germany
HIV-1-specific T-cells can select HIV-1 strains with escape mutations. However, it is still debated whether sequence variation in HIV-1-specific T-cell epitopes is predominantly caused by immune selection or by random mutational events. To investigate the influence of T-cell driven immune selection we analy
309 Anti-HIV Gag Specific CTLs Show an Impaired Proliferative Ability in Untreated Chronically HIV-infected Patients.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 309
Benito J, Soriano V, Lopez M, Lozano S, Martinez P, Gonzalez-Lahoz J; Inst de Salud Carlos III, Madrid, Spain
Different studies have suggested that an impaired function of HIV-specific CTLs could explain its inefficacy to control HIV replication. We have previously found an impaired ability of CTLs to produce IFN-g as well as an immature phenotype. To further explore the functionality of CTLs, the proliferative pot
310 Identification of HIV-1 Pol Cytotoxic T-lymphocyte Epitopes Containing Drug Resistance Mutations.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 310
Mason R, Grant M; Mem Univ of Newfoundland, St John's, Canada
Objectives: Both antiretroviral drugs and cytotoxic T-lymphocytes (CTL) exert selective pressure on HIV. Antiretroviral drug-resistance mutations create a major obstacle to effective long-term therapy of HIV infection. Therefore, therapeutic HIV vaccines should engage both immune and antiretroviral selection pressures,
311 T-cell Receptor Vbeta-repertoire of Immunodominant HIV-specific CD8+ T-cell Population.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 311
Meyer-Olson D, Altfeld M, Brady KW, He S, Lee P, Dranert R, Allen TM, Addo MM, Strick D, Rosenberg ES, Walker BD, Kalams SA; Partners AIDS Res Ctr, Massachusetts Gen Hosp and Harvard Med Sch, Boston, MA
CD8 + T-cells recognizing HIV antigens are believed to be one important contributor of antiviral immune defense and are target to many vaccination strategies. Nevertheless, the knowledge about the T-cell receptor beta variable region (Vbeta) usage of antigen specific CD8 + T-cells in HIV infection is still
312 Induction of HIV-specific CD8+ T-cell Responses in Uninfected Individuals Following Mucosal and Parenteral Exposure to HIV.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 312
Makedonas G, Bruneau J, Alary M, Tsoukas CM, Lowndes C, Lamothe F, Peretz Y, Bernard NF; Immune Deficiency Treatment Ctr, McGill Univ Hlth Ctr Res Inst, Montreal, Canada
HIV-exposed, uninfected subjects (EUs) are more likely to exhibit HIV-specific immune responses than persons at low risk for HIV infection. Here we examine the effect of route of exposure on induction of virus specific immunity. METHODS: Group 1 (n = 21) included persons exposed to HIV via unprotected sex w
313 IL-15 Restores Bcl-2 Levels in HIV-specific CD8+ T-cells from HIV-infected Individuals.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 313
Mueller Y, Petrovas C, Dimitriou I, Bojczuk P, Witek J, Altman J, Katsikis P; Drexel Univ, Philadelphia, PA
We have recently shown that HIV-specific CD8 + T-cells are highly susceptible to CD95/Fas-induced apoptosis, and that this apoptosis is significantly inhibited by IL-15. In this study, we examined the expression of the anti-apoptotic molecules Bcl-2 and Bcl-x L in HIV-specific and total CD8 + T-ce
314 Underestimation of HIV-1 Specific T-cell Responses Directed Against the Autologous Virus using HIV-1 Clade B Consensus Sequences.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 314
Altfeld M, Addo MM, Lee PK, Shankarappa R, Brander C, Allen T, Rathod A, Yu XG, Harlow J, O'Sullivan K, Johnston MN, Strick D, Mullins JI, Rosenberg ES, Walker BD; AIDS Res Ctr, MGH, Boston, MA
The definition of the correlates of protective immunity in HIV requires the determination of the real breadth and magnitude of responses directed against the virus. Comprehensive screening approaches using overlapping peptides spanning the entire expressed HIV sequence of viral reference strains or consensu
315 Recognition of HIV-1 CD8+ T-epitopes in Early Vertical HIV-1 Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 315
Scott Z, Luzuriaga K; Univ of Massachusetts Med Sch, Worcester
Antiretroviral therapy regimens can markedly reduce mother-to-child HIV-1 transmission (MTCT) during the intrapartum period, but do not appear to reduce MTCT through breast milk. A neonatal HIV-1 vaccine could prevent breast milk transmission and provide the basis for lifetime immunity. The characterization
316 Evaluation of Correlates of Protection in HIV-1 Controllers.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 316
Addo MM, Rathod A, Yu XG, Draenert R, Johnston MN, Corcoran C, Davis S, Piechocka-Trocha A, Altfeld M, Rosenberg ES, Walker BD; Partners AIDS Res Ctr, Massachusetts Gen Hosp, Boston, MA
World-wide 40 million individuals are infected with HIV-1, and 14,000 new infections occur everyday. While the majority of individuals progress to disease, a small percentage of individuals control viral replication in the absence of treatment ( Viral Controllers ). Understanding the correlates of protectio
317 HLA-B35 Restricted CD8+ T-cell Responses May Influence Rates of HIV Disease Progression.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 317
Yu J; Univ of Rochester, NY
HIV-1 infected individuals with certain HLA-B35 allelic variants, B3502/3503 (B35-Px), have more rapid disease progression than those with the B3501 (B35-PY) variant. Our previous work showed that the overall magnitude of HIV-specific CD8 + T-cell responses restricted by all class I alleles does not differ
318 The Differential Ability of Long-term Nonprogressors and Progressors to Restrict HIV Replication is Not Caused by Loss of Recognition of Autologous Viral Sequences.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 318
Migueles SA, Laborico AC, Imamichi H, Shupert WL, Royce C, McLaughlin M, Ehler L, Liu S, Metcalf J, Connors M; Lab of Immunoregulation, NIAID, NIH, Bethesda, MD
Whether the impaired restriction of HIV replication observed in most patients (pts) is caused by the loss of CD8 + T-cell recognition of autologous viral sequences remains unknown. Since the production of antigens that are representative of very diverse in vivo variants is not feasible, the frequency of CD8
319 SIV-specific Cytotoxic T-cell Development in SIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 319
Veazey RS, Schmitz JE, Lifson JD, Piatak M, Lackner AA; Tulane Natl Primate Res Ctr, Tulane Univ Hlth Sci Ctr, Covington, LA
Although several studies have examined HIV viral specific T-cells in the blood of HIV-infected humans and SIV infected macaques, few have examined the development and persistence of viral specific cytotoxic T-cells in tissues. In this study, we examined the development of gag-specific CTL in the intestine,
320 Spontaneous Sustained Control of SIVmac239 Infection in a SIV-naïve Rhesus Macaque: Immunologic Correlates.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 320
Lifson JD, Rossio JL, Piatak M Jr, Hoffman AN, Schneider DM, Coalter V, Poore B, Desrosiers RC; AIDS Vaccine Prgm, SAIC Frederick, Inc, NCI, MD
Infection of rhesus macaques with SIVmac239 results in persistent high-level viral replication, progressive immunodeficiency, and opportunistic infections or neoplasms typical of simian AIDS with a median survival of 1-2 yrs post-inoculation. We report on a macaque that spontaneously appears to have establi
321 HIV-1 Regulatory Protein (nef, tat, rev, vif, vpu, vpr)-CTL Responses and Epitope Mapping in Subtype A/E-Infected Thais with CD4 >300 cells/mm3.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 321
Buranapraditkun S, Ruxrungtham K, Sirivichayakul S, Kosonsiriluk S, Kerdsanti S, Hansasuta P, Rowland-Jones S, Phanuphak P; Bangkok, Thailand
There is no data on CTL responses against subtype A/E HIV-1 regulatory proteins. In addition, the HLA polymorphism among Thais is also remarkably different from the western cohorts. Method: CTL responses and epitope mapping and HLA restriction were performed by IFN-gamma ELISpot assay. HIV-1 subtype A/E tru
322 A Novel HLA-Cw1-restricted gag A/E CTL Epitope, YSPVSILDI, Identified in HIV-1 Infected Thai Patients.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 322
Ruxrungtham K, Buranapraditkun S, Hansasuta P, Rowland-Jones S, Sirivichayakul S, Honda M, Warachit P, Phanuphak P; Bangkok, Thailand
Little data has been made on HLA-C restricted, HIV-1 specific CTL responses. HLA Cw1 is found approximately 1/5 th of our cohort (11/60). Our previous study has found a common (37%, 7/19) and new candidate HLA-Cw1 restricted CTL gag epitope, NKIVRMYSPVSILDIKQGPK (20 aa), of HIV-1 subtype A/E in HIV-1 infect
323 Differences in the Expressed HLA Class I Alleles Determine the Differential Clustering of HIV-1-Specific T-cell Responses in Infected Chinese and Caucasians.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 323
Yu XG, Perkins B, Addo MM, Wei F, Rathod A, Parta M, Lee P, Adams C, Wurcel A, Frahm N, Rosenberg ES, Brander C, Cao Y, Walker BD, Altfeld M; Partners AIDS Res Ctr, Mass Gen Hosp /Div of AIDS, Harvard Med Sch, Boston, MA
China is estimated to have one of the world s most rapidly spreading HIV-1 epidemics. Studies providing insights into HIV-1 pathogenesis in infected Chinese are urgently needed to design and test an effective HIV-1 vaccine that prevents infection or attenuates disease in this population. METHODS: HIV-1 spec
324 Cross-reactive HIV-1 Clade B CD8+ T-lymphocytes in Patients Infected with HIV-1 Subtype A/G (CRF02) Living in Ivory Coast (West Africa).
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 324
Inwoley A, Recordon P, Minga A, Gaston J, Dupuis M, Masquelier B, Fleury H, Rouet F, Guillet JG, Andrieu M; CeDReS/PAC-CI, Abidjan, Cote d'Ivoire
Most of HIV vaccine trials are conducted with clade B subtype while the majority of infected individuals living in Africa are contaminated with non-B clade HIV. An efficient vaccine against HIV must induce good cellular immune responses. In order to evaluate the feasibility of a HIV vaccine trial in
325 Nef-specific CD8+ T-cells in HIV-1 Subtype C Infected Individuals Target a Highly Conserved Epitope-rich Central Region Restricted by Novel and Unpredicted HLA Class I Alleles Common in Southern Africa.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 325
Mashishi T, Nyoka S, Mohube P, Khoury G, Paximadis M, Puren A, Donovan R, Williamson C, Sheppard H, Gray C; Natl Inst for Communicable Diseases, Johannesburg, South Africa
Identity of epitope-specific CD8 + T-cell responses to subtype C Nef is important for clade-specific vaccine development. We report on Nef-specific CD8 + T-cell responses of subtype C HIV-1 infected southern Africans restricted by HLA alleles common to this region. Method: A combination of the IFN&#947;
326 Tools for Searching Optimal CTL Epitopes in Reactive Regions.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 326
Yusim K, Calef C, Kommander K, Szinger JJ, Korber BT; Los Alamos Natl Lab, NM
The HIV-1 Immunology Database at www.hiv.lanl.gov is a repository of information about HIV-1 T-cell and antibody epitopes, integrated with the sequence variability data from the HIV-1 Sequence Database. The Immunology database includes tables, maps, and alignments of HIV-specific CTL epitopes that are updat
327 HIV Adaptation to HLA-restricted Immune Responses-Implications for Vaccine Design and Evaluation.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 327
Mallal SA, Moore CB, Carvalho F, Patterson A, Liu C, Goodridge D, Sayer D, James I, John M; Ctr Clin Immunology and BioMed Statistics, Perth, Australia
HIV and ancestral retroviruses have evolved under intense selective pressure from HLA restricted immune responses, consistent with recent evidence of HLA Class I associated viral polymorphisms at a population level. The efficacy of an HIV vaccine will depend on the breadth and strength of HLA restricted imm
328 Sequence Analysis and Identification of CTL Escape.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 328
Liu Y, Nickle DC, Cao J, Zhao H, Genowati I, McNevin J, Davis K, Rose L, McElrath MJ, Mullins JI; Univ of Washington, Seattle
CD8 + cytotoxic T-lymphocyte (CTL) responses are likely to play a critical role in effecting the course of HIV-1 infection. To better understand this role, it is important to identify CTL recognition sites on autologous virus. However, generation and testing of peptides specific to autologous virus is prohi
329 Frequency of CD8 T-cell Responses to Novel HIV-1 Specific Epitopes Among Individuals of Different Racial Backgrounds.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 329
Sabbaj S, Bansal A, Ritter D, Perkins C, Edwards B, Gough E, Tang J, Korber B, Wilson C, Kaslow R, Mulligan M, Goepfert P; Univ of Alabama at Birmingham
Versatile application of vaccines designed to bring forth CD8 + T-cell responses in different racial or ethnic groups will require inclusion of immunodominant T-cell epitopes presented by a variety of class I HLA molecules recognized by a high frequency of individuals. METHODS: To facilitate development of
330 Decreased Immune Activation Drives Naive CD4 T-cell Reconstitution after HAART.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 330
Matthews LT, Sereti I, Natarajan V, Jones E, Chow C, Yoder K, Metcalf JA, Lane HC, Polis MA, Kovacs JA; Natl Inst of Allergy and Infectious Diseases, NIH, Bethesda, MD
HAART therapy leads to substantial reconstitution of HIV induced CD4 lymphopenia and the associated preferential decreases in naïve CD4 populations. However, the contribution of thymic output vs enhanced survival and cell redistribution to this reconstitution are unclear. METHODS: Nineteen (19) HIV-1 infect
331 Modeling the Dynamics of T-cells and TREC After Early and Late Treatment of HIV-1 Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 331
Ribeiro RM, Lewin S, Perelson AS; Los Alamos Natl Lab, NM
The immune processes involved in lymphocyte changes observed under HIV therapy are still controversial. In particular, the relative contributions of decreases in activation (as measured by death and proliferation rates), lymphocyte redistribution, and thymic output are not well understood. METHODS: To quant
332 S Phase Lymphocytes Have a Central Memory Phenotype in HIV Disease.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 332
Sieg S, Valdez H, Lederman M; Case Western Reserve Univ, Univ Hosp of Cleveland, OH
These studies were designed to examine the phenotype of circulating S phase lymphocytes in HIV-infected individuals. METHODS: Whole blood from HIV-infected individuals and healthy donors were incubated with bromodeoxyuridine (BrdU) for 1 h ex vivo and subsequently examined by flow cytometry for the expressi
333 Shortness Lifespan of CD4+ T-cells in SIV-infected Macaques.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 333
Estaquier J, Monceaux V, Cumont MC, Ho Tsong Fang R, Hurtrel B; Inst Pasteur, Paris, France
The dynamic basis for CD4 T-cell depletion in AIDS remains controversial. METHODS: To address this major issue, we explored T-cell dynamic using a new sensitive fluorescent assay to determine direct measurement of circulating T-cell kinetics in peripheral blood of pathogenic and apathogenic SIV-infected mac
334 Early Primary HIV Infection Disrupts Thymic Function as a Result of Impaired Intrathymic Proliferation.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 334
Dion ML, Bordi R, Poulin JF, Sylvestre M, Corsini R, Kettaf N, Boulassel MR, Routy JP, Sekaly RP, Cheynier R; Ctr de Recherche du CHUM, Montreal, Canada
BACKGROUND:The thymus is the main site where thymocytes mature into functional T-cells and has been reported to be affected in HIV pathogenesis. In thymopoiesis, TCRB and TCRA chromosomal rearrangement gives rise to distinct excised DNA molecules, TRECs, a surrogate marker of thymic output. Proliferation-induced TREC d
335 Faster CD4-cell Decline in Individuals with Low TREC Levels before Infection with HIV.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 335
van Asten L, Hazenberg M, Danisman F, Otto S, Roos M, Hamann D, Schuitemaker H, Prins M, Coutinho R, Miedema F; Municipal Hlth Svc, Amsterdam, The Netherlands
Recent thymic emigrants are identifiable by measuring TCR excision circles (TRECs) which are diluted during T-cell division and have been shown to be lower in individuals with chronically stimulated immune systems. TREC content declines with age and is lower in some but not all HIV infected patients (pts).
336 Persistent Immune Activation in HIV-1 Infection is Associated with Naive T-cell Depletion and Progression to AIDS.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 336
Hazenberg M, Otto S, van Benthem B, Roos M, Coutinho R, Lange J, Hamann D, Prins M, Miedema F; Sanquin Res at CLB and Academic Med Ctr, Amsterdam, The Netherlands
HIV-1 infection is characterized by chronic, generalized hyperactivation of the immune system. It was previously shown that increased CD8 + T-cell activation has predictive value for disease progression, but the biological effect of hyperactivation on the immune system in HIV-1 infection is not understood.
337 T-cell Dynamics in HIV-1 Infected Children: A Longitudinal Study on TRECs, T-cell Numbers and Peripheral T-cell Division before and during Antiretroviral Therapy.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 337
Hazenberg M, Borghans J, Otto S, van Rossum A, Scherpbier H, de Groot R, Kuijpers T, Lange J, Hamann D, de Boer R, Miedema F; Sanquin Res at CLB and Academic Med Ctr, Amsterdam, The Netherlands
Interference of HIV-1 with thymic function may be more easily demonstrable in pediatric HIV-1, because thymic output is higher in infants compared to adults. Measurement of T-cell receptor excision circles (TRECs) has been thought to allow quantitative analysis of thymic function. However, apart from thymic
338 CD4 and CD8 T-cell Receptor Repertoire Perturbations with Normal Levels of T-cell Receptor Excision Circles in Therapy Naive, HIV-infected Adolescents.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 338
Pahwa S, Chitnis V, Mitchell RM, Fernandez S, Chandrasekharan A, Wilson CM, Douglas SD; North Shore Long Island Jewish Res Inst, New York Univ Sch of Med, Manhasset
The REACH Project (Reaching for Excellence in Adolescent Care and Health) of the Adolescent Medicine HIV/AIDS Research Network is an observational study of HIV-infected- and high-risk HIV-uninfected adolescents, ages 13-18 yrs at enrollment from 15 different clinical sites in 13 U.S. cities. These youth acq
339 Bone Marrow Is a Preferential Anatomic Site for Homeostatic Proliferation of Mature T-cells in Primates.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 339
Paiardini M, Cervasi B, Muthukumar A, Barry A, Sumpter B, McClure H, Mittler R, Piedimonte G, Staprans S, Sodora DL, Feinberg MB, Silvestri G; Emory Univ, Atlanta, GA
The numeric homeostasis of T-cells is maintained by virtue of a balance between thymic differentiation (TD), antigen-driven proliferation (ADP), and homeostasis-driven proliferation (HDP). We hypothesize that perturbations of HDP may be involved in the pathogenesis of AIDS in HIV-infected humans and SIV-inf
340 SIV-induced T-cell Depletion in Macaques is Followed by Elevated IL-7 Levels and T-cell Proliferation at Times Prior to Simian AIDS and Death.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 340
Muthukumar A, Gauduin MC, Johnson RP, McClure HM, Silvestri G, Sodora DL; Univ of Texas Southwestern Med Ctr, Dallas
Interleukin (IL)-7 levels are elevated as a homeostatic response to various T-cell depleting conditions. T-cell depletion in HIV-infected patients (pts) has been correlated with increased IL-7 levels. Furthermore, elevated IL-7 levels have been touted as an indicator of HIV disease progression. Studies pres
341 Intermittent IL-2 Administration to HIV-infected Patients Leads to Polyclonal Expansion of the CD4 T-cell Pool.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 341
Sereti I, Matthews L, Hahn B, Imamichi T, Berg S, Davey R, Lane HC; Natl Inst of Allergy and Infectious Diseases, NIH, Bethesda, MD
Intermittent administration of IL-2 cycles to HIV-infected patients (pts) leads to preferential expansion of CD4 + /CD25 + cells, a large proportion of which have a naïve phenotype. It is currently unclear if IL-2 cycles induce polyclonal expansion with CD25 expression and proliferation of previously CD4
342 Perforin-Expressing CD4+ T-cells are Found in Oligoclonal Expansions and Decline in the Setting of HAART.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 342
Goodwin L, Bennett S, Connick E, Kotzin B; Univ of Colorado Hlth Sci Ctr, Denver
Perforin-expressing CD4 + T-cells have been reported quite recently in HIV infection. We previously described two HIV-infected individuals with expansions in CD4 + cells that express T-cell receptor variable-beta chains (VB) 2.1 and 6.7 that contained multiple clones, which persisted over 3 years of HAART a
343 Different Levels of Immune Activation in Naive and Memory Subsets of CD4 and CD8 T-lymphocytes in Chronic HIV Infection-Effects of Antiretroviral Therapy.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 343
Benito J, Lopez M, Lozano S, Martinez P, Gonzalez-Lahoz J, Soriano V; Inst de Salud Carlos III, Madrid, Spain
Expression of CD38 on T-lymphocytes has been used as a marker of immune activation in HIV infection and has prognostic value on disease progression, independently of CD4 + counts. However, little is known about the differential expression of this molecule in naïve versus memory subsets of both CD4 and CD8 T
344 Spontaneous Apoptosis of T-lymphocytes Fails to Normalize on Long-term HAART and Strongly Predicts the Recovery of CD4 T-lymphocytes.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 344
Kaufmann G, Hansjee N, Strub C, Weber R, Battegay M, Erb P; Univ Hosp Basel, Switzerland
The depletion of CD4 T-lymphocytes is a hallmark of HIV-1 infection and mostly the result of T-cell apoptosis. The long-term effect of potent antiretroviral therapy (HAART) on T-cell apoptosis was investigated. METHODS: Spontaneous apoptosis (SA) and cellular apoptosis markers were evaluated in 55 HIV-1 inf
345 Lymphoproliferative Responses to HIVp24 in Chronically HIV-1 Infected Patients Treated with HAART Reflect Low-level Viral Replication but Not an Improvement in Indices of Immune Phenotype or Function.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 345
Lange CG, Patterson BK, Harnish B, Medvik K, Xu Z, Asaad R, Valdez H, Lee SJ, Landay A, Lieberman J, Lederman MM; Ctr for AIDS Res, Case Western Reserve Univ, Univ Hosp of Cleveland, OH
While CD4 + T-cells may be needed to sustain CD8 + T-cell activity in chronic viral infection, it has been difficult to dissect the cause-and-effect relationship between preservation of CD4 + T-cell helper function and control of HIV-replication. METHODS: Functional immune responses to vaccination (immune r
346 Older Age is Associated with Reduced Naive T-cell Responses to Antiretroviral Therapy: 48-week Results of ACTG Protocol 5015.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 346
Kalayjian R, Lederman MM, Pollard RB, Pu M, Spritzler J, Stocker V, Chernoff M, Fiscus S, Taub D, Valcour V, Mantz N, Rousseau F, Olsen J, Brun S, Landay A; MetroHlth Med Ctr, Cleveland, OH
Objective: Older age is a strong predictor of accelerated HIV-disease progression, both in the presence and in the absence of HAART. To identify potential immune correlates of this interaction, we compared the viral and immune responses to a uniform antiretroviral regimen according to age. METHODS: Multi-center, prospe
347 Shifting Pressure Affects the Frequency of CD8+ T-cell Escape Variants with Initiation of HAART.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 347
Casazza J, Betts M, Hill B, Brenchley J, Ambrozak D, Douek D, Koup R; Vaccine Res Ctr, NIH, Bethesda, MD
In HAART-treated patients (pts), HIV is under pressure from the immune response and antiretroviral therapy. The varying pressures exerted by these 2 entities may be reflected in the viral quasispecies. Method: Five (5) pts were screened for CD8 + T-cell responses to HIV using intracellular cytokine staining
348 Suppression of HIV Replication with HAART Can Induce de novo Appearance of HIV-specific CTLs in Patients with Chronic HIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 348
Lopez M, Soriano V, Benito J, Lozano S, Martinez P, Gonzalez-Lahoz J; Inst de Salud Carlos III, Madrid, Spain
Most previous studies have shown that HIV-specific cytotoxic CD8 + lymphocytes (CTLs) tend to decline after suppressing viral replication with HAART. However, in some individuals CTL activity can be maintained or even develops after beginning HAART. Herein, we used tetrameric complexes to analyze the effect
349 Repertoire of HIV-1 p24 Epitopes Targeted by CD4+ T-cells in HIV-1 Infected Subjects Either Receiving or Not Receiving Antiretroviral Therapy.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 349
Boritz E, Palmer B, Wilson C; Univ of Colorado Hlth Sci Ctr, Denver
CD4 + T-cell recognition of multiple HIV-1-derived epitopes during HIV-1 infection may contribute to effective HIV-1-specific immunity. In a pilot study, we found a diverse repertoire of HIV-1 p24-specific CD4 + T-cell clones in a subject who began ART during advanced HIV-1 disease. To pursue this further,
350 HIV-specific Cytotoxic T-lymphocyte Epitope Responses in HIV-infected Children on HAART.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 350
Ching N, Ank B, Yang O, Nielsen K, Deville J, Bryson YJ; Univ of California at Los Angeles
HIV-specific Cytotoxic T-lymphocyte (CTL) epitope responses have been reported in adults treated early in HIV infection associated with containment of acute viremia and in those with chronic infection. However, data on HIV CTL responses in infants and children have been limited with detection rare in young
351 Predictors of HIV-specific Immune Responses in Chronically HIV-infected Subjects on Antiretroviral Therapy.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 351
Siddique A, Dragileva E, Hartman KE, Campagna J, Cherng DW, Dondero M, Peiperl L, Valentine F, Kalams SA; Partners AIDS Res Ctr and Massachusetts Gen Hosp, Boston, MA
The identification and longitudinal follow-up of cell-mediated immune responses to HIV proteins will be important for evaluating the effect of immunotherapeutic vaccines. Some current protocols exclude subjects with low CD4 T-cell nadirs out of fear that these subjects will not be able to respond to vaccine
352 Protease Inhibitor-containing HAART is Associated with Decreased In Vivo T-cell Activation Independent of its Effects on Viral Replication.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 352
Hunt P, Martin J, Bangsberg D, Moss A, Sinclair E, Bredt B, Deeks S; Univ of California at San Francisco
A reduction in T-cell activation may mediate the immunologic benefit of HAART in HIV-infected patients (pts), even among those with sub-optimal virologic responses. While protease inhibitors (PI) directly inhibit activation-induced T-cell apoptosis in vitro, it is unknown whether PI-based HAART decreases in
353 HAART Alters the Natural Evolution of the Pattern of HIV-specific Immune Responses in Subjects Starting HAART in Primary HIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 353
Alter G, Hatzakis G, Tsoukas CM, Rouleau D, LeBlanc RP, Baril JG, Dion H, Lefebvre E, Thomas R, Cote P, Routy JP, Sekaly RP, Bernard NF; McGill Univ Hlth Ctr, Montreal, Canada
HIV-specific CD8 + T-cell responses that appear early in HIV primary infection (PI) are believed to play a role in controlling viral replication, although they fail to clear virus. Host-virus interactions early in HIV infection are thought to impact on subsequent HIV course of disease. Hypothesis: HAART alt
354 Treatment, Immunological Changes, and Pregnancy Outcome.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 354
Fiore S, Newell ML, Trabattoni D, Savasi V, Tibaldi C, Lanzani C, Conserva V, Ferrazzi E, Clerici M; Univ Coll of London, UK
It has been shown that type 2 cytokines increase and type 1 cytokines decrease during normal pregnancy, and that weak type 2 cytokine production may adversely affect pregnancy outcome. Progression of HIV infection is also suggested to be associated with a type 1-to-type 2 shift, and antiretroviral therapy (
355 Immunologic Evidence that Start of ART can be Deferred for CD4 T-cell Count < 200/mul.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 355
Nobile M, Correa R, Ellefsen-Lavoie K, Aschwanden E, Spasojevic M, D'Agostino C, Codarri L, Khonkarly M, Pantaleo G; Lab of AIDS Immunopathogenesis, CHUV, Lausanne, Switzerland
Recent studies have shown that ART is still effective in patients (pts) with CD4 T-cell counts down to 200 cells/micro-l in preventing the progression of HIV disease and in the recovery of CD4 T-cells, thus indicating that start of ART can be deferred for CD4 T-cell counts > 200/micro-l. The immunologic mec
356 The Interaction of DC-SIGN with HIV-1 gp120.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 356
Lekkerkerker A, van Vliet S, van Kooyk Y, Geijtenbeek T; Free Univ Med Ctr, Amsterdam, The Netherlands
DC-SIGN, a novel dendritic cell (DC) cell-surface C-type lectin, plays a key role in the dissemination of HIV-1. DC-SIGN captures HIV-1 at mucosal sites of entry through binding of the gp120 envelope glycoprotein of HIV-1, facilitating the transport to lymphoid tissues, where DC-SIGN on the DC can transmit
357 Transmission of Cell-surface Bound Human Immunodeficiency Virus Type 1: Interaction Between Cell-surface LFA-1 and Virus-bound ICAM-1 Take Over Interactions Between Cell-surface DC-SIGN and Virus-anchored gp120/ICAM-3.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 357
Bounou S, Giguere JF, Cantin R, Tremblay MJ; Infectious Diseases Res Ctr, CHUL, Faculty of Med, Laval Univ, Quebec, Canada
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. The primary objective of this study was to define whether the nature o
358 DC-SIGN Interactions with Feline Immunodeficiency Virus.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 358
de Parseval A, Su SV, Elder J, Lee B; Scripps Res Inst, La Jolla, CA
DC-SIGN, a specific C-type lectin expressed on dendritic cells, binds and transmits multiple strains of primate immunodeficiency viruses to susceptible cells. Under limiting amounts of cognate viral entry receptors, DC-SIGN can also facilitate the efficiency of virus infection when expressed in cis. Feline
359 HIV Envelope (gp120) Binding to DC-SIGN and Primary Dendritic Cells is Carbohydrate Dependent but Does Not Involve 2G12 or Cyanovirin Binding Sites: Implications for Structural Analyses of gp120 DC-SIGN Binding.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 359
Hong PW, Flummerfelt K, de Parseval A, Gurney K, Elder J, Lee B; Univ of California at Los Angeles
The calcium-dependent lectin, DC-SIGN, binds to HIV (and SIV) gp120 and mediates the binding and transfer of HIV from monocyte-derived dendritic cells (MDDCs) to permissive T-cells. However, it has been recently reported that DC-SIGN binding to HIV gp120 may be carbohydrate independent. Here, we formally de
360 DC-SIGN Mediated Transmission of HIV-1 is Cell Type Restricted.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 360
Wu L, Martin TD, Han YC, Breun SK, KewalRamani VN; NCI-Frederick, MD
DC-SIGN, an ICAM-3 receptor that is expressed on the surface of dendritic cells (DC), is the first known example of a virus attachment receptor that works most potently in trans. Through a high affinity interaction with primate lentiviral envelope glycoproteins, DC-SIGN captures virus and promotes the trans
361 Structure-function Studies of DC-SIGN Interactions with gp120, ICAM-2, and ICAM-3.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 361
Stephen V. Su SV, Hong P, Flummerfelt K, Negrete O, Lee B; Geffen Sch of Med at UCLA, Los Angeles, CA
DC-SIGN, a mannose-specific C-type lectin that binds avidly to the gp120 of HIV/SIV, is implicated in the transmission of HIV from dendritic cells (DCs) to permissive T-cells. ICAM-2 and ICAM-3, endogenous ligands for DC-SIGN, mediate transendothelial migration of DCs and T-cell/DC clustering, respectively.
362 Mechanisms of HIV-1 Attachment to Immature Dendritic Cells.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 362
Gummuluru R, Rogel ME, Emerman M; Fred Hutchinson Cancer Res Ctr, Seattle, WA
Background. In contrast to the CD4/chemokine receptor complex that mediates virus-cell fusion and entry, HIV-attachment factors do not mediate fusion of the virus and the host cell membranes, but rather could internalize virus particles by receptor-mediated endocytosis. Such mechanisms of virus accumulation not only ha
363 Role of pH in the DC-SIGN/HIV Interaction.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 363
Davis C, Pohlmann S, Leslie G, Baribaud F, Doms R; Univ of Pennsylvania Sch of Med, Philadelphia
DC-SIGN, a type II membrane protein with a C-type (calcium dependent) lectin domain that is highly expressed on mucosal dendritic cells (DCs) and certain macrophages in vivo, binds to the glycoproteins of human and simian immunodeficiency viruses (HIV and SIV), Ebola virus, and Hepatitis C virus. HIV captur
364 HIV-1 and Other Pathogens Target DC-SIGN to Affect Immune Responses.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 364
Geijtenbeek T, van Vliet S, Koppel E, Sanchez-Hernandez M, Appelmelk B, van Kooyk Y; VU Med Ctr, Amsterdam, The Netherlands
The dendritic cell (DC)-specific C-type lectin DC-SIGN play an important role in the HIV-1 pathogenesis. HIV-1 is efficiently captured by DC-SIGN on DC at mucosal tissues. HIV-1 escapes the DC-SIGN-mediated antigen presentation route, and hides as infectious particles in non-lysosomal compartments during tr
365 Variations of Dendritic Cells Subsets, NK Cells Proportions and Functions in the First Days of Rectal SIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 365
Petitprez K, Kahi S, Couedel-Courteille A, Lebon P, Hosmalin A, Butor C; Cochin Inst, Paris, France
Dendritic cells (DC) are absolutely required to activate naïve T-cells and play a role in antiviral innate immunity by secreting type I interferon (IFN). A cross-talk between DC and resting NK cells may also contribute to the innate defense during viral infections. Two (2) major populations of DC are found
366 Development of Soluble DC-SIGN and Characterization of HIV Binding Activity.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 366
Jia H, Li J, Butera ST; HIV and Retrovirology Branch, CDC, Atlanta, GA
The contribution of dendritic cells to mucosal HIV transmission may be largely mediated via surface expression of DC-SIGN, a C-type lectin, to which HIV envelope proteins selectively adhere. The adherence processes may be sensitive to inhibitors that interfere with the DC-SIGN-gp120 interaction. METHODS: A
367 DC-SIGNR Oligomers Binding to gp120, Deglycosylated gp120 and ICAM-3.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 367
Snyder GA, Colonna M, Sun PD; Natl Inst of Allergy and Infectious Diseases, NIH, Rockville, MD
DC-SIGN and related DC-SIGNR bind high mannose oligosaccharides on HIV-1 viral particle envelope glycoprotein gp120 enhancing virus infection efficiency by a mechanism that is not completely understood. DC-SIGN is a C-type lectin containing a short intracellular signaling domain, a transmembrane domain, a r
368 Characterization of DC-SIGNR Transcript Isoforms from Human Dendritic Cells and Rectum Biopsies.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 368
Liu H, Hladik F, Nelson PJ, Lee J, Corey L, McElrath MJ, Zhu T; Univ of Washington, Seattle
DC-SIGNR and DC-SIGN may bind HIV-1 and mediate efficient infection of CD4 + T-lymphocytes in trans. It was reported that alternative splicing of DC-SIGNR and DC-SIGN pre-mRNA generated a wide repertoire of transcripts encoding membrane associated and soluble isoforms. Total of 9 DC-SIGNR transcript isoform
369 Cytokine Regulation of DC-SIGN Expression in Human Monocytes and Effect on HIV-1 Transmission.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 369
Chehimi J, Azzoni L, Luo Q, Shawver L, Ngoubilly N, June R, Jerandi G, Papasavvas E, Montaner L; Wistar Inst, Philadelphia, PA
Originally described by its binding properties to HIV envelope glycoproteins, Dendritic Cell Specific ICAM3 Grabbing Nonintegrin (DC-SIGN) plays a key role in the initiation of immune responses through DC-T-lymphocytes clustering. In addition, DC-SIGN, expressed in a variety of DC mediates efficient HIV tra
370 Attempt to Localize the Binding of DC-SIGN on gp120.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 370
Ford J, Atibalentja D, Arthos J, Sun P; Natl Inst of Allergy and Infectious Diseases, NIH, Rockville, MD
The binding of DC-SIGN to HIV envelope protein gp120 facilitates and enhances HIV infection to T-cells. It is known that DC-SIGN binds to some of the 12 high mannose moieties on gp120 through its carbohydrate recognition domain. Carbohydrates on gp120 can be visualized in 2 sections, one on the silent face
371 Mutational Analysis of the DC-SIGN Cytoplasmic Tail in the Mechanism of HIV-1 Transmission.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 371
Breun S, Baumann J, Martin T, KewalRamani V; NCI-Frederick, MD
Dendritic cells (DCs) are among the first cells that encounter HIV-1 when it penetrates the mucosa. DCs pulsed with low amounts of HIV-1 efficiently transmit it to primary CD4 + T-cells. Molecular insight to this process was obtained in the characterization of the dendritic cell-restricted molecule known as
372 Study of the Role of Mannose Binding Lectine and DC-SIGN in Discordant Partners in a Haiti Cohort.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 372
Mohri H, Sakai T, Mushtaq N, Fitzgerald D, Pape JW, Johnson WD, Ho DD; Aaron Diamond AIDS Res Ctr, New York, NY
The envelope protein of HIV-1, gp120 is enriched in high-mannose oligosaccharides. Therefore, glycoprotein-lectin interactions may be crucial for HIV-1 transmission. Mannose binding lectin (MBL) is known to delay the disease progression. However, its role in HIV-1 transmission is well characterized. At muco
373 Genetic Polymorphisms in DC-SIGNR Repeat Region Affect HIV-1 Transmission.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 373
Liu H, McElrath MJ, Holte S, Celum C, Lee J, Corey L, Zhu T; Univ of Washington, Seattle
DC-SIGN and DC-SIGNR efficiently bind and transmit HIV-1 to susceptible cells in trans. Both DC-SIGN and DC-SIGNR are organized into 3 domains: an N-terminal cytoplasmic region, a neck region containing 7 repeats of the 23 amino acid sequence, and a C-terminal domain with homology to C-type lectins. DC-SIGN
374 Increased Natural Killer Cell Activity in HIV-1 Exposed but Uninfected Vietnamese Intravascular Drug Users.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 374
Scott-Algara D, Truong LX, Versmisse P, David A, Tram LT, Ngai NV, Theodorou I, Barre-Sinoussi F, Pancino G; Inst Pasteur, Paris, France
Innate immunity might contribute to protection from HIV-1 infection. We addressed this question by studying NK cell function in a population of Vietnamese HIV-1 exposed intra-vascular drug users (IDU) who, despite more than 10 years of high-risk behaviours, remain apparently uninfected (EU). METHODS: Thirty
375 Innate Immunity in HIV Infection: Effect of HIV Envelope-NK Cell Interactions.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 375
Kottilil S, Shin K, Planta AM, Arthos J, Fauci AS; Lab of Immunoregulation, NIAID, NIH, Bethesda, MD
We have previously demonstrated that NK cells from HIV-infected individuals are defective in their ability to suppress endogenous HIV replication. We further analyzed the molecular mechanisms involved in NK-cell HIV interactions in vitro using HIV envelopes derived from primary isolates as well as R5 and X4
376 Enhancement of Natural Killer Cell Number and Cytokine-driven Activation in HIV-1+ Patients Recieving Growth Hormone and HAART.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 376
Goodier M, Imami N, Moyle G, Rennalls L, Gazzard B, Gotch F; Imperial Coll Faculty of Med, Chelsea and Westminster Hosp, London, UK
Natural Killer (NK) cells are reduced in number, have altered surface expression of inhibitory receptors (CD94-NKG2A), and have impaired functional capacity during chronic untreated HIV infection. As observed for CD4 + T-cells, NK cell numbers are recovered, at least in part, during highly active anti-retro
377 Critical Role of NKp44L, the Ligand of the Activated Natural Cytotoxicity Receptor NKp44 in the CD4+ T-cells Depletion During HIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 377
Viellard V, Strominger JL, Debre P; INSERM U543, Hosp Pitie-Salpetriere, Paris, France
Natural killer (NK) cells participate in the innate immune responses against HIV. The ability of NK cells to kill virus-infected cells is regulated by a balance between inhibitory and activating receptors. A novel emerging group of receptors, the natural cytotoxicity receptors (NCRs) are responsible for NK
378 Tight Regulation of Primary Cytotoxic Response by Innate Helper Cells and its Impairment by Persisting Viruses.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 378
Rouzine IM, Murali-Krishna K, Ahmed R; Tufts Univ, Boston, MA
Knowing exactly how different CTL types interact with each other when responding to a viral threat, and why they fail to clear some viruses, would be very instrumental in developing vaccines and antiviral drugs. In addition to experimental studies of particular cases, this requires finding a mathematical mo
379 HIV Infection is Associated with Expanded Mucosal gamma delta T-cells, which may Explain Changes in Peripheral gamma delta T-cell Counts.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 379
Poles MA, Barsoum S, Sun P, Ho D, Zhang L; New York Univ Sch of Med, New York
Gamma delta T-cells, potentially important components of the innate immune response against HIV, are primarily found in the gastrointestinal mucosa. METHODS: We utilized flow cytometry to phenotype lymphocytes derived from the peripheral blood and from colonic biopsies of HIV-infected and uninfected subject
380 Local Delivery of CpG ODN Induces a Mucosal Innate Antiviral State and Prevents Genital HSV-2 Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 380
Ashkar AA, Rosenthal KL; McMaster Univ Hlth Sci Ctr, Hamilton, Canada
Mucosal surfaces are the entry site for the vast majority of infectious pathogens and provide the first line of defense against infection. In addition to the epithelial barrier, the innate immune system plays a key role in recognizing and rapidly responding to invading pathogens. Since CpG oligodeoxynucleot
381 The Role of Cytokines which Signal through the Common Gamma Chain Cytokine Receptor in the Reversal of HIV-1 Specific CD4+ and CD8+ T-cell Anergy.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 381
Gu J, Kovacs C, Ostrowski M; Univ of Toronto, Canada
There is increasing evidence that HIV-1 specific T-cells are anergic in vivo. The frequencies of HIV-1 specific IFN-g producing CD4 + T-cells detected in natural infection are markedly lower when compared to other viral infections, like CMV . HIV-1 specific IFN-g producing CD8 + T-cells are demons
382 Association of Mannose-binding Lectin B Allele with Slower Progression to AIDS in Perinatally HIV-1 Infected Children but Not with HIV-1 Vertical Transmission.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 382
Mangano A, Mecikovsky D, Lusso S, Bologna R, Sen L; Hosp Natl de Pediatria "Prof Dr Juan P Garrahan," Buenos Aires, Argentina
When the specific immune system is damaged, innate immunity might take a leading role in combating infections. Mannose binding lectin (MBL) is one of the most important components of innate immunity. Thus, the participation of MBL as a host factor in HIV-1 infection should to be evaluated mainly in children
383 Reductions of Serum Melatonin Levels in HIV-1 Infected Individuals Parallel Disease Progression: Correlation with Serum Interleukin-12 Levels.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 383
Nunnari G, Nigro L, Palermo F, Leto D, Pomerantz RJ, Cacopardo B; Thomas Jefferson Univ, Philadelphia, PA
During the natural history of human immunodeficiency virus type I (HIV-1) infection, an impairment of interleukin-12 (IL-12) production precedes a switch from a T-helper 1 to a T-helper 2 stage of cellular immunity. Melatonin, the main hormone produced by the pineal gland, seems to promote a T-helper 1 resp
384 Comparison of the Efficacy of gp120-based Immunogens in Transgenic Mice Producing Human IgGs.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 384
He Y, Honnen W, Kayman SC, Pinter A; Publ Hlth Res Inst, Newark, NJ
An effective approach for identifying epitopes that mediate neutralization of primary HIV-1 isolates is the isolation of monoclonal antibodies with neutralizing activities. Recently, we demonstrated that transgenic mice engineered to produce human IgGs (XenoMouse from Abgenix, Inc.) produced a broad range o
385 Morphine Enhances HIV Infection of Human Blood Mononuclear Phagocytes through Modulation of beta-Chemokines and CCR5 Receptor.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 385
Guo CJ, Li Y, Tian S, Wang X, Douglas SD, Ho WZ; Children's Hosp of Philadelphia, PA
Injection drug use (IDU) remains a significant risk for acquiring human immunodeficiency virus (HIV) infection. Although it is known that opiates such as morphine suppresses immune system and promotes HIV infection in vitro, the mechanisms by which morphine enhances HIV infection of human immune cells remai
386 Differential Regulation of IL-7 Receptor (CD127) by TNFalpha and IL-7: Implications for HIV Immunopathogenesis.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 386
Komsic A, Young CD, Angel JB; Ottawa Hlth Res Inst, Ottawa, Canada
IL-7 and its signaling via the IL-7 receptor (IL-7R/CD127) are required for normal CTL activity. Our previous observation that down-regulation of this receptor is observed on CD8 + T-cells of HIV infected individuals and is restored with effective therapy suggests that this may contribute to impaired CTL ac
387 A Non-secreted Variant of Interleukin-4 is Associated with Apoptosis-Implication for Th2 Polarization in HIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 387
Ledru E, Fevrier M, Lecoeur H, Garcia S, Boullier S, Gougeon ML; Inst Pasteur, Paris, France
The cytokine network and the apoptotic pathway exhibit multiple regulatory interactions. In HIV-infected persons, both death receptor induced apoptosis and deprivation apoptosis are increased and have been proposed to contribute to T-cell deletion associated to this disease. Deprivation apoptosis is related
388 HIV Inhibition of IL-12 Synthesis is Mediated by Altering MAPK Activity and Nuclear Factor Binding to the IL-12p40 Promoter.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 388
Frappier FM, Chambers KA, Angel JB; Ottawa Hlth Res Inst Univ of Ottawa, Canada
IL-12 is critical for the generation of cellular immune responses and its production is impaired in HIV infection. LPS and other agents can stimulate IL-12 synthesis, but the signaling pathways that lead to its production are not well characterized. We have previously shown that HIV directly inhibits IL-12p
389 HIV gp120 and CD4 Binding Induces Activation of STAT1, STAT3, and STAT5 in Promonocytes and Macrophages.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 389
Kohler J, Gavegnano C, Sleasman J, Goodenow M; Univ of Florida, Coll of Med, Gainesville
Signal transducer and activator of transcription (STAT) proteins are cytoplasmic transcription factors that translocate to the nucleus when activated and regulate gene expression as mediators of cytokine and growth factor stimulation. Several viruses, including Human Immunodeficiency Virus (HIV-1), have bee
390 Increased Sensitivity of Peripheral Lymphocytes from HIV-1 Infected Individuals to CD4- and CXCR4-mediated Apoptosis.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 390
Ritsou E, Breitkreutz R, Benner A, Bohler T, Weigand MA, Walczak H, Gougeon ML, Krammer PH; Inst Pasteur, Paris, France
Stimulation of the CD4 and CXCR4 receptors by the HIV-1 envelope glycoprotein gp120 or specific antibodies has been previously shown to induce a novel type of apoptosis in T-cells. This was induced via both the CD4 and CXCR4 receptors and was CD95 (Apo-1/Fas) and caspase independent. In this study, we inves
391 Increased hEKLF Levels in HIV-1 Infected Macrophages: A Differential Role for hEKLF in Regulating IL-12 p40 Promoter through Newly Identified CACCC Region and Modulation of the NFkB Pathway.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 391
Luo Q, Ma X, Ngoubilly N, Wahl S, Bieker J, Crossley M, Montaner LJ; Wistar Inst, Philadelphia, PA
The mechanism for suppression of IL-12 production in HIV infection remains undetermined. Here we describe a CACCC box (-224 to -220) as a newly identified transcriptional cis-element on the IL-12 p40 proximal promoter associated with constitutive repression, which is modulated in IFNg/LPS and IL-10 regulati
392 No Changes in Immune Activation Phenotypes, Response to Antigen, or CD8+ T-cell Mediated HIV Suppression in Transplant Recipients Receiving Immunosuppression.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 392
Roland M, Stablein D, Bredt B, Munoz-Marino B, Carlson L, McCune J, Levy J, Rogers R, Stock P; Univ of California at San Francisco
HIV infection is associated with loss of naïve T-cells, activation of memory T-cells, loss of CD4 + T-cell proliferative responses to recall antigens and T-cell mitogens, and loss of normal responses to antigen by activated CD8 + T-cells. Cyclosporine (CsA) may reduce immune activation-associated HIV pathog
393 Promoter Analysis of Early Response Genes Induced by Chemokine Receptor Signaling.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 393
van 't Wout AB, Westreich DJ, He H, Nickle DC, Mullins JI; Univ of Washington, Seattle
Most HIV-1 variants can be divided into 2 groups based on their chemokine coreceptor usage, with CCR5 and CXCR4 identified as the coreceptors for HIV-1 R5 and X4 variants, respectively. These variants have biological significance, since the emergence of X4 variants predicts a more rapid disease progression.
394 Prostratin Induces Internalization and Degradation of HIV-specific Receptor and Co-receptor through Activation of Novel PKCs.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 394
Hezareh M, Dudognon P, Pondarzewski M, Brown SJ, Carpentier JL, Foti M; AIDS Res Alliance, West Hollywood, CA
Prostratin, a non-tumor promoting phorbol ester exhibits potent antiviral activity against acute infection by multiple strains of HIV. It also activates viral gene expression from latently infected cells. Prostratin s lack of tumor and its ability to up-regulate latent HIV-1 provirus expression could be exp
395 HIV-1 Tat Reprograms Immature Dendritic Cells to Express Chemoattractants for Activated T-cells and Macrophages.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 395
Izmailova E, Bertley F, Huang Q, Makori N, Miller CJ, Young RA, Aldovini A; Children's Hosp, Harvard Med Sch, Boston, MA
Immature dendritic cells are among the first cells infected by retroviruses after mucosal exposure, and pathogen-host interactions during early stages of infection can have a profound influence on later stages of infection. METHODS: We explored the effects of HIV-1 and its Tat transactivator on these primar
396 Adjuvant Effects of an NKT Ligand, alpha-Galactosylceramide, on DNA Vaccination.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 396
Huang Y, Chen Z, Zhang W, Song Y, Gurner D, Gardiner D, Chen A, Tsuji M, Ho DD; Aaron Diamond AIDS Res Ctr, Rockefeller Univ, New York, NY
DNA vaccines show great promise as an alternative to conventional vaccination in numerous animal models; however, results from human trials suggest that their immunogenicity may be limited. Recently, the natural killer T-cell (NKT) ligand, alpha-galactosylceramide (alpha-GalCer), has been shown to have adju
397 CTLA4-mediated APC Targeting Enhanced the Humoral and Cellular Immune Responses of an SIV DNA Vaccine in Mice.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 397
Zhang W, Chen Z, Huang Y, Song Y, Ho DD; Aaron Diamond AIDS Res Ctr, Rockefeller Univ, New York, NY
DNA vaccines can elicit both humoral and cellular immune responses, and offer a useful approach to preventing HIV-1 infection. However, results from clinical trials to date suggest that DNA-based vaccines are only weakly immunogenic in humans. We sought to improve the immunogenicity of a DNA vaccine by targ
398 CpG Stimulation of Interferon-gamma Production In Vitro is Modified by IL-10 and B-cells.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 398
Kuruppu JC, Lore K, Ross RW, Seder RA, Koup RA; Vaccine Res Ctr, NIH, Bethesda, MD
Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs are potent immunomodulators and are of great interest as potential adjuvants in HIV vaccine development. ODN have been shown to activate cells carrying Toll-like receptor 9 (TLR-9) found on plasmacytoid dendritic cells (PDC), B-cells,
399 IL-15 Enhances both Prophylactic and Immunotherapeutic Vaccines When Used in Combination with HIV-1 DNA Vaccines.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 399
Weiner DB, Kutzler M, Robinson T, Lewis M, MacGregor RR, Boyer JD; Univ of Pennsylvania, Philadelphia
We have tested HIV-1 DNA vaccines in both non-human primates studies as well as phase I clinical studies. We have demonstrated HIV-1 DNA vaccines are safe and immunogenic. However, these studies have also demonstrated that the induced HIV-1 specific CD8 cellular immune response must be increased above the c
400 Enhancement of Immune Responses to HIV-1 by DNA Vaccination Using the Complement Protein, C3d.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 400
Ross T, Green T, Sodroski J, Bower J; East Carolina Univ, Sch of Med, Greenville, NC
A central problem for the development of DNA vaccines has been to identify immunogens capable of raising high titer, long lasting, neutralizing antibody to surface viral glycoproteins. HIV-1 envelope (Env) has proven to be a weak immunogen, raising low titer antibodies that are slow to undergo affinity matu
400a Safe and Effective Use of CpG as Adjuvant for HBV Vaccination in HIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 400a
Cooper CL, Davis HL, Morris ML, Seguin I, Angel JB, Elfer SM, Cameron DW; Univ of Ottawa at the Ottawa Hosp, Ottawa, Ontario, Canada
Non-protective response to HBV vaccine occurs in HIV infection. CpG oligodeoxynucleotide 7909 activates plasmacytoid dendritic cell function and promotes Th-1 biased immune response, may greatly increase immunogenicity of vaccination in general, and may restore vaccine responsiveness in hyporesponsive perso
401 Molecular Epidemiology of HIV-1 Among Northern Thai Drug Users: Implications for HIV Vaccine Efficacy Trials.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 401
Beyrer C, Tovanabutra S, Suriyanon V, Juttiwutikarn J, Razak MH, Celentano DD, Birx D, McCutchan F; Johns Hopkins Univ, Baltimore, MD
We conducted a large cross-sectional (n = 1865) and seroincidence (n = 880) cohort study among Thai drug users (IDU and non-IDU) in Chiang Mai Province to assess risks for HIV, identify prevention targets, prepare for HIV vaccine and other intervention trials, and assess current HIV-1 molecular epidemiology
402 Early Markers of HIV-1 Disease Progression in a Prospective Cohort of Seroconverters in Bangkok, Thailand: Implications for Vaccine Trials.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 402
Buchacz K, Hu D, Vanichseni S, Chaowanachan T, Srisuwanvilai L, Mock P, Kitayaporn D, van Griensven F, Tappero J, Keawkungwal J, Choopanya K, Mastro T; CDC, Atlanta, GA
Some new candidate HIV-1 vaccines may not prevent HIV-1 infection, but may mitigate the course of disease. Phase III efficacy trials of such vaccines will require the evaluation of surrogate endpoints among HIV-1-infected persons before the initiation of antiretroviral therapy (ART). Since high HIV-1 RNA le
403 Vaccine-induced Positive HIV Serology Among Participants in 10 Clinical Trials of Canarypox-vectored HIV Vaccine Trials in the U.S.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 403
Sullivan P, Rossini T, deBruyn G, Russell N, Chiu Y, Belshe R, Keefer M, Guranathan S, Eastman D; Fred Hutchinson Cancer Res Ctr, Seattle, WA
Preventive HIV vaccines may stimulate recipient immune responses which result in positive HIV serology results (vaccine-induced positivity, VIP). VIP responses are important because they may result in social harm, discrimination, or distress to recipients and may necessitate further laboratory testing. METH
404 PACTG 326: A Phase I/II Study to Evaluate the Safety and Immunogenicity of Alvac HIV Vaccines Alone and with AIDSVax B/B in Children Born to HIV-infected Mothers: Preliminary Results.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 404
Johnson D, McFarland E, Muresan P, Fenton T, Lambert J, McNamara J, Hawkins E, Bouquin P, Read J, Estep S, Gunurathan S, Gurwith M; Mt Sinai Hosp, Chicago, IL
ALVAC-HIV vCP1452 (1452) (Aventis Pasteur) vaccine is a modified recombinant Canarypox virus expressing products of HIV-1 env, gag, nef and pol genes. AIDSVAX B/B (B/B) ( VaxGen ) is a bivalent vaccine containing 2 different subtype B gp 120 antigens. METHODS: PACTG 326, a randomized, placebo controlled, do
405 Vaccination in Humans Generates Broad T-cell Cytokine Responses.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 405
Rosa SC, Lu FX, Perfetto SP, Moser S, Miller CJ, Evans TG, Roederer M; Vaccine Res Ctr, Natl Inst of Hlth, Bethesda, MD
Determining in vitro T-cell responses to candidate vaccines is one measure of immunogenicity and may also be a potential indicator of vaccine efficacy. T-cell responsiveness is commonly determined by in vitro stimulation with antigenic proteins or peptides followed by assaying for an effector cytokine such
406 Improving the Quality of the CTL Response with Peptide Mimetopes of an HIV Native Epitope.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 406
Kan-Mitchell J, Wilson DB, Rinaldo CR, Hegde R, Cao T, Blondelle S, Wong C; Wayne State Univ Sch of Med, Detroit, MI
Background. Virus-specific CTL responses are critical in the control of HIV-1 infection and their induction will play an important part in therapeutic and prophylactic HIV vaccines. The high levels of HIV-specific CTLs induced by the natural infection are clearly inadequate to eradicate the virus, with the majority of
407 The Protective Effect of Passively Transferred Neutralizing Antibody in the Setting of Active Cellular Immunity.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 407
Mascola J, Lewis M, VanCott T, Stiegler G, Katinger H, Shiver J, Poignard P, Burton D, Letvin N; Vaccine Res Ctr, NIAID, NIH, Bethesda, MD
Current HIV vaccine candidates elicit reasonably potent cellular immune responses, but only low levels of neutralizing antibodies. Such CTL based vaccines (e.g., those based on DNA immunization) do not prevent infection, but can have a beneficial effect on disease course. In contrast, passively infused anti
408 Induction of Broadly Cross-reactive Primary Isolate Neutralizing Antibodies by Env-CD4 Complexes.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 408
Srivastava IK, Kan E, Sharma V, Sun Y, Ulmer JB, Barnett SW; Chiron Corp, Emeryville, CA
The successful HIV vaccine should induce strong humoral and cellular responses at appropriate sites. HIV Env protein is the target for inducing broad primary isolate neutralizing antibody responses. However, gp120 monomer is rather limited in its ability to induce R5 isolate-specific neutralizing antibody r
409 Ancestral HIV-1-B Env Protein Induces Broadly Neutralizing Antibodies in Rabbits.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 409
Learn G, Doria-Rose N, Mahalanabis M, Rodrigo AG, Li F, Haigwood NL, Mullins JI; Univ of Washington, Seattle
HIV-1 has proven to be an extremely difficult target for vaccine development, in part because of its capacity to mutate to escape immunologic recognition. Furthermore, circulating strains are becoming more and more divergent with time. Thus, one conundrum facing vaccine developers is the choice of viral str
410 Development of a Consensus Env Immunogen for HIV-1 Group M.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 410
Gao F, Li Y, Rodenburg CM, Alam M, Beddows S, Moore JP, Liao HX, Haynes BF, Korber BT, Hahn BH; Duke Univ Med Ctr, Durham, NC
Globally circulating strains of HIV-1 exhibit an extraordinary degree of genetic variation, which constitutes a major obstacle to AIDS vaccine development. To test whether immunogen based on a consensus sequence could minimize this diversity, we generated a universal env gene (gp160) from the consensus sequ
411 Dichotomy in Cross-clade Reactivity of Sera: Implications for the Development of Active and Passive Immunotherapy.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 411
Cavacini L, Duval M, Wood C, Mayer K, Posner M; Beth Israel Deaconess Med Ctr and Harvard Med Sch, Boston, MA
Using sera and virions from clade B infected individuals, we have shown previously that serum antibodies reactive with primary isolate virions correlates with virus neutralization and stable disease. While clade B is responsible for the vast majority of infections in North America and parts of Europe, infec
412 Maturation of Humoral Antibody in HIV-1 Subtype B or E Infections Following Seroconversion.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 412
Parekh B; CDC, Atlanta, GA
A better understanding of maturation of humoral immune response in HIV infection may help in the evaluation of antibody responses in different subtype infections and development of subtype-independent serologic assays for detecting recent HIV infection for incidence estimates. METHODS: Longitudinal specimen
413 The Nature of Heterologous Neutralization by HIV+ Serum.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 413
Gibson M, Skema C, McDanal C, Kurtzer J, Smith C, Tomaras G, Montefiori D, Jack N, Cleghorn F, Blattner W, Weinhold K, LaBranche C; Duke Univ Med Ctr, Durham, NC
Eliciting relevant neutralizing antibodies (nAbs) is a major challenge of HIV vaccine research. NAbs to autologous virus arise in most HIV-infected individuals, and sera from some individuals neutralize heterologous primary isolates. However, the epitopes recognized by nAbs in vivo are not well understood,
414 Identification of Epitopes Involved in Escape from Neutralizing Antibody.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 414
Tomaras GD, Goodman DG, McDanal CB, Jack N, Cleghorn F, Blattner WA, Weinhold KJ, Mathews TJ, Greenberg ML; Duke Univ, Durham, NC
The detection of viruses that evolve to escape antibody neutralization in HIV infection indicates that neutralizing antibodies are exerting immunological pressure on the virus in vivo. We hypothesize that particular regions of the HIV envelope involved in this escape can be mapped through a direct compariso
415 Enhanced Immunogenicity to HIV-1 Envelope Using DNA Vaccines.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 415
Bower JF, Sodroski J, Ross T; East Carolina Univ, Sch of Med, Greenville, NC
Recent studies suggest that HIV-1 envelope (Env) is a trimer on the native virus particle. In addition, it has been proposed that oligomeric/trimeric envelope vaccines may elicit better neutralizing antibodies because they more closely mimic the native conformation of gp160 Env. Two soluble, trimeric envelo
416 Creating Novel HIV-1 gp120 and gp120Core Molecules Sharing Similar Antigenicity to the Native Trimeric Envelope Complex Using DNA Shuffling Technology.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 416
Du X, Xu L, Zhang W, Parren P, Zwick M, Burton D, Whalen R; Maxygen, Inc, Redwood City, CA
An efficient prophylactic vaccine is the ultimate solution to the rapidly emerging AIDS/HIV epidemic. Although HIV-1 gp120 is highly immunogenic, most antibodies induced by monomeric gp120 hardly recognize the trimeric envelope complex on primary isolates and fail to block viral infection. Creating novel gp
417 A Single-round, Recombinant-based Viral Infectivity Assay Allows for the Sensitive and Specific Detection of Biologically Relevant Neutralizing Antibodies to HIV-1.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 417
Decker J, Wei X, Wang S, Wu X, Hahn B, Kappes J, Shaw G; Howard Hughes Med Inst, Univ of Alabama at Birmingham
Infection of human cells by R5 and X4 HIV-1 viruses is a complicated, multi-step process that lies at the heart of viral persistence and pathogenesis. Furthermore, inhibition of virus infection represents a primary objective in HIV-1 vaccine design. Assay methods are needed which measure biologically-releva
418 Defining Mechanisms of Antibody-mediated Neutralization of SIV.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 418
Cole KS, Steckbeck J, Miller K, Orlov I, Bruno J, Werkman J, Polansky N, Puffer B, Doms R, Montelaro R; Univ of Pittsburgh, PA
The ability of neutralizing antibodies to block infection from both parenteral and mucosal infections in passive protection experiments has been demonstrated. However, the mechanisms of this neutralization process remain unclear. One hypothesis is that neutralization sensitivity is related to the density of
419 SIV env gp140 "Domain-specific" Antibody Responses in Rhesus Macaques Inoculated with Attenuated SIV/17E: A Novel Strategy to Understanding Delayed Humoral Maturation.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 419
Rowles J, Cole KS, Sturgeon T, Jin J, Murphey-Corb M, Montelaro RC; Univ of Pittsburgh Sch of Med, PA
The identification of reliable immune correlates of AIDS vaccine protection in the SIV/monkey vaccine model has proven elusive. Using qualitative assays of antibody conformational dependence and avidity, we have previously described a complex evolution of envelope-specific antibody responses associated with
420 Defined Sequence Variants of Simian Immunodeficiency Virus Strain 239 Reveal Global Effects on Sensitivity to Antibody-mediated Neutralization.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 420
Johnson W, Sanford H, Lifson J, Parren P, Burton D, Robinson J, Desrosiers R; New England Reg Primate Res Ctr, Southborough, MA
Primary isolates of HIV and SIV are highly resistant to antibody-mediated neutralization. We used SIV239, a molecularly cloned pathogenic SIV, to investigate the factors that determine the neutralization-resistant phenotype. METHODS: We studied a collection of genetically altered derivatives of the neutrali
421 CD4-independent Co-receptor Use of Sequential SIVsm Isolates Varies with the Neutralizing Antibody Response.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 421
Vodros D, Thorstensson R, Doms RW, Fenyo EM, Reeves JD; Karolinska Inst, Stockholm, Sweden
Co-receptor use of sequential SIVsm re-isolates from experimentally infected cynomolgus macaques with fast or slow disease progression and known neutralizing antibody pattern was previously tested in GHOST(3) indicator cells. We found that CCR5 use was highly efficient and stable over time. BOB/gpr15 and CX
422 Tat Protein Production in Plants; A New Approach to Mucosal Delivery of an HIV-1 Vaccine Candidate.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 422
Karasev AV, Shon KJ, Aiamkitsumrit B, Zwierzynski I, Koprowski H; Thomas Jefferson Univ, Doylestown, PA
The HIV-1 Tat protein has been recently explored as a prospective vaccine candidate with broad, subtype non-specific action. We approached the problem of delivery of Tat through the mucosal route, e.g., mimicking the normal route of HIV-1 entry into the body, by expressing Tat in an edible plant, like spina
423 Evaluation of MHC Alloimmunization as an HIV Vaccine Strategy Using SIV/Macaque Model.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 423
Guan Y, Luscher MA, Rakasz E, Watkins DI, Rustam T, Candido M, Tartaglia J, MacDonald KS; Univ of Toronto and Mount Sinai Hosp, Canada
The molecules of the major histocompatibility complex (MHC) are prominent among cellular proteins incorporated in the virion of both HIV and SIV. MHC molecules are immunogenic and vary significantly between individuals, yet are not subject to rapid mutation unlike viral proteins, so they are potential immun
424 Study of Allo-immunization in Humans During Sexual Intercourse and Effects on HIV Infectivity.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 424
Peters BS, Whittal T, Bubaahmady K, Gray K, Vaughan R, Lehner T; King's Coll, London, UK
The potential for HLA antigens to elicit an allo-immune response deserves study, particularly as allo-immunization induces potent immune responses, and there is evidence that allo-immunization in macaques may protect against SIV. This study aims determine whether unprotected (UP) vaginal intercourse in wome
425 Comparison between Intradermal and Intramuscular Routes of Administration in the Induction of Multispecific CD8+ Lymphocytes in Rhesus Macaques Vaccinated with NEF and GAG Derived Lipopeptides.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 425
Coutsinos Z, Villefroy P, Gras-Masse H, Beyer C, Guillet JG, Bourgault-Villada I; Cochin Inst, Paris, France
The importance of cytotoxic T-lymphocytes (CTLs) in the control of HIV/SIV replication is well documented. Magnitude and breadth of CTL responses are factors that are likely to influence the effectiveness of CTLs. Indeed broad multi-specific CTLs, induced by vaccination, control viral load, and appear to re
426 Long-term Specific Immune Responses Induced in Humans by an HIV-1 Lipopeptide Vaccine: Immunodominance Ranking of CD8+ T-cell Epitopes.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 426
Gahery-Segard H, Pialoux G, Figueiredo S, Igea C, Surenaud M, Gras-Masse H, Levy JP, Guillet JG, Guillet JG; INSERM U567, Paris, France
We have shown previously that an anti-HIV lipopeptide vaccine using large peptides derived from regulatory or structural HIV-1 proteins (Nef, Gag, and Env) injected alone or with QS21 adjuvant to HIV-uninfected volunteers is well tolerated and is able to induce immune responses already after three injection
427 Preclinical Testing of an HIV-1 Envelope-containing Heat-treated Pseudovirion Vaccine.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 427
Poon B, Hsu JF, Gudeman V, Negrete O, Chen IS, Grovit-Ferbas K; David Geffen Sch of Med at UCLA, Los Angeles, CA
One of the major obstacles in the development of vaccines to target neutralizing antibody responses is the relative neutralization-resistance of primary HIV-1 isolates. The use of pseudovirions provides a complex antigen source with close to native conformation is one approach that could be taken to develop
428 Transduction of Human Dendritic Cells Using Attenuated Salmonella typhimurium as a Vaccine Strategy against HIV-1.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 428
Gurner D, Huang Y, Ho DD; Aaron Diamond AIDS Res Ctr, Rockefeller Univ, New York, NY
The promise of genetic immunization is limited in part because of its invasive, untargeted administration. Here we describe successful refinement of the strategy by incorporating attenuated bacteria that deliver DNA plasmids directly to antigen presenting cells. Specifically, we show that human dendritic ce
429 High Cellular Immune Responses to SIV Antigens following Recombinant DNA Prime and Listeria Monocytogenes Boost in the Rhesus Macaque Model.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 429
Boyer JD, Robinson T, Lewis M, Carlarota S, Weiner DB, Paterson Y; Univ of Pennsylvania, Philadelphia
There is a pressing need for an effective vaccine against human immunodeficiency virus (HIV) type 1. Furthermore, an HIV-1 specific cell mediated immune response will most likely be important in the ultimate control of HIV-1 replication. Recombinant Listeria monocytogenes has demonstrated the ability to ind
430 Recombinant Yeast Vaccine Induces Maturation of Human Dendritic Cells in HIV-1 Infected Patients.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 430
Barron M, Blyveis N, Wilson C; Univ of Colorado Hlth Sci Ctr, Denver
Despite the success of HAART in the treatment of individuals with HIV-1, such therapeutic combinations have limitations. The application of HAART with a therapeutic vaccine has the potential to improve HIV-1 specific immunity. Dendritic cells (DCs) are likely to play a critical role in the induction of cell
431 Ancestral State Reconstructions in the Formulation of HIV Vaccines.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 431
Mullins JI, Learn GH, Li F, Rodrigo AG; Univ of Washington, Seattle
HIV replication results in a high mutation rate that permits rapid generation of viruses that can escape immune recognition. HIV sequences sampled from a population of infected individuals recapitulate a star burst-like evolutionary tree pattern; most of the variants sampled at the same time are positioned
432 New Murine Model for HIV-1 Infection and Rapid Vaccine Screening.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 432
Ayash-Rashkovsky M, Borkow G, Davis H, Moss RB, Bentwich Z; Hebrew Univ Med Sch, Jerusalem, Israel
Abstract not available.
433 AIDS Vaccines That Allow HIV-1 to Infect and Escape Immunological Control: A Mathematical Analysis of Mass Vaccination.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 433
Bogaards JA, van Ballegooijen M, Boerlijst MC, Weverling GJ, Goudsmit J; Academic Med Ctr, Univ of Amsterdam, The Netherlands
HIV vaccine concepts shown to reduce viremia and postpone disease, but not prevent infection in monkeys, are currently in human Phase I trials. The key question is if widespread application of such vaccines could have a significant impact on the AIDS epidemic in the developing world. To study their potentia
434 Parasitic Infection Alters the Quality of the Immune Response to HIV-1 Vaccines.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 434
Boyer JD, Robinson T, Artis D, Weiner DB, Scott P; Univ of Pennsylvania, Philadelphia
More than 95% of all HIV-infected people now live in the Developing World, and 95% of all deaths have occurred among its people. In these countries, chronic parasitic infection adds another level of complexity to AIDS vaccine development. Helminthic and protozoan infections are common in developing countrie
434a Prime-Boost Vaccination with Recombinant Mycobacterium bovis Bacillus Calmette-Guerin and Vaccinia Strain DIs Elicits Protective Immunity against Pathogenic SHIV Infection in Macaques.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 434a
Yamamoto N, Nakasone T, Izumi Y, Matsuo K, Ami Y, Yamazaki S, Honda M; National Institute of Infectious diseases,Japan
Currently, many candidate vaccines against HIV-1 utilize multi-component viral proteins for the induction of strong HIV-specific immune responses. However, the potential of SIV candidate vaccines expressing single viral proteins has not been fully explored. Mycobacterium bovis bacillus Calmette-Guerin (BCG)
435 Using Immunostimulatory Cytokines Delivered by rSV40 Vectors to Generate Powerful and Long-lasting Cell-mediated Immune Responses Against HIV Envelope gp120.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 435
McKee HJ, Strayer DS; Jefferson Med Coll, Philadelphia, PA
Immunostimulatory cytokines (e.g., IL-12 and IL-15 into the regimen) may promote adaptive immune responses and cytotoxic memory, respectively, and so facilitate long-term non-progression to AIDS in HIV infection. A promising approach to anti-HIV vaccine development is use of live virus vectors to deliver HI
436 Immunization Against SIV Gag Using Recombinant SV40 Vectors Elicits Strong, Durable Cell-mediated Immune Responses.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 436
McKee HJ, Strayer DS; Jefferson Med Coll, Philadelphia, PA
A promising approach to anti-HIV vaccine development is the use of live virus vectors to deliver HIV antigens in vivo. The parameters of protective immunity against HIV infection remain unclear, but strong cell-mediated immune responses are likely to be very important. Since recombinant SV40 vectors (rSV40s
437 Construction and Characterization of Herpes Simplex Virus-derived AIDS Vaccine Vectors.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 437
Brockman M, Watanabe D, Mathews L, Knipe D; Harvard Med Sch, Boston, MA
Vaccines against HIV have not been developed. We observed that HSV vectors induced durable host immunity in mice and macaques. In addition, some macaques vaccinated with HSV vectors expressing SIV proteins were protected against SIV challenge. These results indicated that HSV might be a good vector for gene
438 Intranasal Vaccine Subunit Priming Followed by MVA Boosting Enhances the Induction of HIV-specific IFNgamma Spot-forming Cells and Tetramer Positive T-cells in the Female Reproductive Tract.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 438
Peacock J, Nordone S, Jackson S, Liao HX, Letvin N, Gomez-Yafal A, Gritz L, Mazzara G, Haynes B, Staats H; Duke Univ Med Ctr, Durham, NC
HIV-specific cytotoxic T-cells in the female reproductive tract (FRT) may contribute to vaccine-induced protection against sexually-transmitted HIV. METHODS: Various prime/boost immunization regimens using HIV Env Th-CTL peptide, DNA or MVA expressing an HIV-1 Env T-helper determinant and Env (p18) H-2D d
439 Towards Better Strategies for Poxvirus-based HIV Vaccines: Studies of the Cellular Tropism of Modified Vaccinia Ankara and Vaccinia Virus in Primary Human Cells.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 439
Chahroudi A, Chavan R, Liu L, Waller EK, Silvestri G, Feinberg MB; Emory Univ, Atlanta, GA
Attenuated pox viruses such as Modified Vaccinia Ankara (MVA) have generated significant interest as vectors for HIV vaccines. However, many features of MVA s interaction with the host immune system are poorly understood. In particular, the range of cellular targets within the immune system and the immediat
440 Design, Construction, and Testing of a Multi-valent Recombinant Modified Vaccinia Ankara Vaccine for Use Against the Dominant Circulating C/B Recombinant Form of HIV-1 in China.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 440
Chen Z, Huang Y, Zhao X, Ba L, Zhang W, Song Y, Gurner D, Ho DD; Aaron Diamond AIDS Res Ctr, New York, NY
The rapid spread of HIV-1 in China has called for the urgent development of a prophylactic vaccine. Using live Modified Vaccinia Ankara (MVA) as a vehicle, we have successfully designed and constructed a multivalent vaccine specifically for Yunnan, China, where a circulating C/B recombinant form of HIV-1 is
441 Efficient Human Immunodeficiency Virus-like Particles Formation from a Single Semliki Forest Virus Replicon.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 441
Kim E, Shin HJ, Shin KS, Kim HS, Kim CJ; Coll of Veterinary Med, Chungnam Natl Univ, Soeul, Korea
Future AIDS vaccine candidates should generate strong, broad and long-lasting CTL and neutralizing antibody response. To ensure the safety and efficacy for AIDS vaccine, VLPs with native conformation could be the another candidate. We produced the replicative and non-replicative Human Immunodeficiency Virus
442 A Novel Adenovirus Recombinant Vaccine to HIV-1.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 442
Pinto AR, Gao G, Wilson JM, Ertl HC; Wistar Inst, Philadelphia, PA
Human recombinant adenovirus has been studied extensively as vaccine carrier for antigens from different pathogens including those from HIV-1. Although they can induce a very strong cellular and humoral immune response, giving promising results as vaccines, the pre-existing immunity of humans is expected to
443 Longitudinal Analysis of Vaccinated Macaques after Partial Control of Primary SIVmac239 Infections.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 443
Matano T, Lun W, Kano M, Takeda A, Nakamura H, Mori K, Sata T, Nagai Y, Sugiura W; Natl Inst of Infectious Diseases, Tokyo, Japan
We previously developed a DNA vaccine and a recombinant Sendai virus (SeV) vector vaccine and showed their potential for inducing virus-specific cytotoxic CD8 + T cells (CTL) efficiently in macaque AIDS models. Recent preclinical AIDS vaccine trials including ours showed CTL-associated control of immunodefi
444 SIV Promoter Exchange Results in a Highly Attenuated Strain that Strongly Protects Against Pathogenic Challenge Virus.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 444
Blancou P, Chenciner N, Ho Tsong Fang R, Monceaux V, Cumont MC, Guetard D, Hurtrel B, Wain-Hobson S; Harvard Univ, Boston, MA
Among the many simian immunodeficiency virus (SIV) immunogens only live attenuated viral vaccines have afforded strong protection to a natural pathogenic isolate. To date there has been a general inverse correlation between attenuation and protection. As the viral promoter is crucial to the tempo of replica
445 Innate and Adaptive Immune Responses to Infection of Macaques with Pathogenic and Attenuated SIV Strains.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 445
Fultz PN, Wei Q, Tao B, Vance P, Lifson J, Piatak M, Hoxie JA; Univ of Alabama at Birmingham
During the early phases of HIV or SIV infections, little is known about the role of innate immunity, its effects on viral replication, and the transition to adaptive immunity. To determine whether there are differences in immune responses elicited by pathogenic versus attenuated viruses during infection of
446 Molecular Biology and Immunobiology of Infection with a Replication Incompetent HIV-1.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 446
Wang B, Dyer W, Zaunders J, Kelleher A, Sullivan J, Saksena N; Westmead Hosp, Sydney, Australia
Truly non-progressive HIV-infected individuals comprise of only 0.8% of total HIV-infected population. These individuals have undetectable plasma viremia, high CD4 + and CD8 + T-cell counts, strong immune responses and remain therapy naïve. Here we have studied one such rare individual who displays strong a
447 Enhanced DNA Prime-protein Boost Vaccines Induce Potent and Protective Immune Responses Against HIV-1.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 447
Barnett S, Srivastava I, Stamatatos L, zur Megede J, Lian Y, Otten G, Montefiori D, Lewis M, Engelbrecht S, van Rensburg EJ, Widera G, O'Hagan D, Polo J, Ulmer J, Donnelly J; Chiron Corp, Emeryville, CA
Novel vaccine approaches will be required to induce potent and durable immunity against diverse HIV-1 strains. METHODS: Sequence-modified gene cassettes were constructed expressing the gag, pol, and env antigens derived from subtypes B and C HIV-1 strains. In addition to naked DNA, 2 different DNA vaccine d
448 Novel Forms of DNA Vaccines Decrease Viremia Upon SIVmac251 Challenge.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 448
Rosati MR, Carney P, von Gegerfelt A, Valentin A, Tryniszewska E, Franchini G, Markham P, Venzon D, Miller N, Felber BK, Pavlakis GN; Natl Cancer Inst, Frederick, MD
Efficient high-level expression of genes expressing HIV and SIV structural proteins independent of the Rev/RRE regulatory system has been achieved by RNA (codon) optimization. Although such vectors induce both humoral and cellular immune responses in mice, they induce good cellular immune responses but low
449 Specific, Efficient, and Short-lived DNA Expression in Lymph Node Dendritic Cells Mediates DermaVir's Immunotherapeutic Effects.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 449
Lori F, Trocio J, Galluzzi L, Markham P, Fox C, Lisziewicz J; Res Inst for Genetic and Human Therapy, Washington, DC
Based on the postulate that HIV pathogenesis is largely mediated by viral expression in the lymphoid organs, a DNA-based topical vaccine (DermaVir) was designed to target Langerhans cells (LC) and ultimately be expressed by dendritic cells (DC) in the lymph nodes, thereby eliciting a T-cell mediated immune
450 Vector Components and Intracellular Process that May Influence the Expression and Immunogenicity of Codon-optimized HIV-1 Env DNA Vaccines.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 450
Wang S, Farfan D, Shen S, Hirsch A, Xing Y, He F, Giehl T, Lu S; Univ of Massachusetts, Worcester
Optimized gene construction and expression are critical for the final immunogenicity of novel gene based HIV-1 vaccines. The current study is conducted to understand other vector components and intracellular process which can further influence the immunogenicity of codon-optimized HIV vaccines. METHODS: The
451 Design, Purification, and Immunological Testing of DNA Vaccines against HIV-1.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 451
Murashev BV, Masharsky AE, Murasheva IV, Romanovich AE, Dukhovlinov IV, Pavlova MS, Dukhovlinova YN, Dorofeyeva YS, Galatchiants YP, Klimov NA, Kozlov AP; BioMed Ctr, St Petersburg, Russia
The development of the series of plasmid constructions based on the LAI HIV-1 and Russian region-specific HIV-1 subtype A. METHODS: Standard methods of DNA cloning were employed. The pNL4-3 (NY5/LAI) and plasmids containing Russian region-specific HIV-1 subtype A genes were used. Codon preference of the A s
452 The Effect of Single-site versus Multiple-site DNA vaccination on Immune Responses in Mice.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 452
Gardiner D, Huang Y, Chen Z, Gurner D, Leung L, Song Y, Tsuji M, Ho D; Aaron Diamond AIDS Res Ctr, New York, NY
Immune responses to antigens encoded by DNA vaccines generated in small animals are robust. However, studies in humans typically show limited immunogenicity, possibly due to dose limitations. We hypothesized that vaccination at different anatomical sites might improve the responses seen with low-dose DNA in
453 Effective Induction of Virus-specific Immunity Induced by Rectal or Nasal DNA-MVA Vaccination and its Effect on SHIV Challenge.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 453
Bertley FM, Wang SW, Kozlowski P, Carville A, Mansfield KG, Johnson RP, Lifson J, Aldovini A; Children's Hosp, Harvard Med Sch, Boston, MA
Transmission of HIV infection occurs predominantly via mucosal routes. The ability of vaccines to induce mucosal immunity may be a necessary requirement for protection against HIV infection and AIDS. METHODS: We have investigated the immuno-stimulatory properties of a DNA vaccine, which produces SHIV partic
453a Magnitude and Diversity of Cytotoxic T-lymphocyte Responses Elicited by Multiepitope DNA Vaccination in Rhesus Monkeys.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 453a
Subbramanian RA, Kuroda MJ, Charini WA, Barouch DH, Costantino C, Santra S, Schmitz JE, Shiver JW, Letvin NL; Harvard Medical School, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, Massachusetts
During the course of HIV/SIV infection, CTL responses develop a predictable bias in their pattern of epitope recognition with most of the CTL response being focused on only a very limited number of epitopes. Accumulating evidence suggests that an effective HIV vaccine must elicit a high frequency CTL respon
454 Seminal Super Shedding of HIV: Implications for Sexual Transmission.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 454
Taylor S, Sadiq T, Sabin C, White D, Cane P, Drake S, Pillay D; Univ of Birmingham and Birmingham Heartlands Hosp, UK
HIV-1 is usually detected in seminal plasma (SP) less frequently than the corresponding blood plasma (BP) and usually at lower levels. However, in most cohorts there are a significant minority of men in which SP levels are equal to, or higher than BP levels. We have identified these individuals as seminal s
455 Seminal Reservoirs During an HIV-1 Eradication Approach.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 455
Nunnari G, Kulkosky J, Leto D, Sullivan J, Xu Y, Pomerantz RJ; Thomas Jefferson Univ, Philadelphia, PA
Despite of the reduction of the levels of HIV-1 virions in blood and seminal plasma of HIV-1-infected patients (pts), HAART does not eradicate HIV-1 disease. Low-levels of viral replication can be shown in pts with undetectable plasma HIV-1 RNA load, and viral rebound occurs after interruption of therapy. R
456 Differences in HIV-1 Replication Dynamics between Peripheral Blood and Vagina Suggest a Compartmentalized Viral Production in the Female Genital Tract.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 456
Andreoletti L, Chomont N, Gresenguet G, Matta M, Matta M, Coudol P, Belec L; Fac de Med de Reims, France
The female genital tract is suspected to be an independent compartment of HIV-1 replication, which would have significant implications for HIV-1 transmission and for the design of systemic and mucosal vaccination against HIV. METHODS: In the present study, the levels of cell-free HIV-1 RNA and proviral DNA
457 Determination of Viral DNA in T-cells and Monocytes/Macrophages in the Cervix and Blood of HIV+ Women.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 457
Prakash M, Patterson S, Gotch F, Kapembwa M; Imperial Coll, London, UK
Heterosexual transmission is the predominant route of HIV infection. To further understand the dynamics of sexual transmission and levels of virus persistence following the initiation of HAART, CD4 + bearing cells capable of harbouring virus were isolated and the level of viral DNA quantitated. METHODS:Twen
458 Human Urogenital Epithelial Cells Capture Cell-free HIV-1 and Transmit the Virus to CD4+ Cells-Implications to Mechanisms of Sexual Transmission.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 458
Wu Z, Chen Z, Phillips D; Univ of Pennsylvania, Philadelphia
Sexual transmission of HIV-1 has become the dominant route of the epidemic, especially in parts of the world where preventative resources are limited, therapeutics are inaccessible to the majority of the population, and genital-related illnesses are prevalent. However, despite profound understanding of the
459 Mucosal CCR5 Expression is Down-regulated in HIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 459
McGowan I, Elliott J, Taing P, Fuerst M, Boscardin J, Anton P; David Geffen Sch of Med at UCLA, Los Angeles, CA
CCR5 is a key receptor for HIV infection and has been identified on CD4 + lymphocytes in both blood and intestinal mucosa. In seronegative controls, CCR5 expression is increased in mucosa compared to in blood. Following HIV infection, the predominant viral tropism is for the CCR5 receptor and CCR5 expressio
459a The Prostate as a Reservoir for HIV-1.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 459a
Smith DM, Kingery JD, Ignacio CC, Wong JK, Richman DD, Little SJ; Univ of California, San Diego
Introduction: HIV in the genital tract is often genetically distinct from that in the bloodstream. This variation results from differing host cell selection, local immune responses, and varying penetration of drugs into the genital tract. Male genital secretions are a complex mixture of cells and secretions from the te
460 Resistance of HIV Infection in Resting Memory CD4+CD62L- T-lymphocytes In Vitro to Drugs Used in HAART.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 460
Gondois-Rey F, Biancotto B, Vigne H; INSERM, Marseille, France
The persistence of HIV in resting memory CD4 T-lymphocytes presents one of the major obstacle in the virus eradication. These cells form a reservoir of HIV that persists in infected individuals in spite of an early application of HAART and a successful control of plasma viremia. We previously demonstrated i
461 CD45RO+ Cells which are Latently Infected with HIV Co-express CD45RA.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 461
Cao Y, Saavedra-Lozano J, Xu J, McCoig X, Ramilo O, Vitetta ES; Univ of Texas Southwestern Med Ctr, Dallas
Despite the success of HAART, cells which are latently infected with HIV remain in treated individuals. These cells are predominately CD45RO + , but some reports suggest that CD45RA + cells can also act as an HIV reservoir. We have reported that latently-infected cells can be eliminated with an immunotoxin
462 An In Vitro Model for the Study of Latent/Persistent HIV-1 Infection in Primary CD4 Cells: Quantitation of Integrated Viral DNA Using Real-time PCR.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 462
Koelsch KK, Kawano Y, Wong JK, Richman DD, Spina CA; Univ of California at San Diego, La Jolla
Viral latency is a major obstacle in the treatment of HIV infection. In vivo studies of viral and host factors that contribute to the establishment of latent HIV infection in CD4 T-cells are hindered by the low frequency of latently infected cells (1-10 per 106 circulating CD4 cells). To circumvent this pro
463 Multiply Spliced and Extracellular PBMC-associated HIV-RNAs are Specific Cellular Correlates of Productive Infection Early after Cessation of HAART.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 463
Fischer M, Joos B, Hirschel B, Weber R, Gunthard HF; Univ Hosp Zurich, Switzerland
HIV-1 may replicate at low levels in patients (pts) successfully treated with HAART, but quantification of residual replication remains difficult. To identify potential correlates of ongoing HIV-1 replication, we studied kinetics of cell-associated multiply spliced and unspliced HIV-1 RNAs in PBMC during ea
464 Longitudinal Study of Replication Competent HIV from CD4 T-cell "Latent" Reservoirs in HIV-infected Children on HAART.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 464
Ching N, Wei LS, Deville J, Nielsen K, Wolinsky S, Dickover R, Bryson YJ; Univ of California at Los Angeles
CD4 T-cells have been shown to harbor replication competent HIV (RCV) in both children and adults on HAART with prolonged undetectable plasma viremia. METHODS: We prospectively evaluated 11 HIV-infected infants and children (35 days to 9-yrs-old) and 1 teenager (16 yrs) with durable plasma viremia suppressi
465 The Persistence of Morphological and T-lymphocyte Subsets Abnormalities in Lymphoid Tissue in HIV-1 Infected Patients Successfully Treated with HAART Correlate with Lymphoid Tissue Viral Replication.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 465
Alos L, Morente V, Garcia F, Caballero M, Mestre G, Cruceta A, Arnedo M, Pumarola T, Plana M, Gallart T, Martinez E, Mallolas J, Blanco JL, Miro JM, Gatell JM; Inst d'Investigacions Biomediques August Pi i Sunyer, Hosp Clin, Univ of Barcelona, Spain
Patients (pts) successfully treated with HAART still have abnormalities in lymphoid tissue (LT). A complete lymph node recovery may not be possible or may be linked to a persistence of viral replication. METHODS: Fourteen (14) HIV-infected persons in early stages (baseline lymphocytes T CD4 + > 500) treated
466 Persistence of Stable, Quantifiable Viremia in Patients on Antiretroviral Therapy Despite Suppression of Plasma HIV-1 RNA to less than 50 Copies/ml.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 466
Maldarelli F, Wiegand A, Palmer S, Kearney M, Boltz V, Polis M, Falloon J, Mican J, Davey R, Rock D, Liu S, Planta A, Metcalf J, Mellors J, Coffin J; HIV Drug Resistance Prgm, NCI, NIH, Frederick, MD
Potent antiretroviral therapy is effective in suppressing but not eradicating HIV-1 infection. Antiretroviral drug resistance leading to treatment failure can evolve despite initial suppression of HIV-1 RNA to below the limit of detection of current assays. HIV-1 RNA assays of greater sensitivity and precis
467 CCR7 Expression of T-cells and CD16 Expression on CD14+ Monocytes Determine the Predominant Cellular Reservoirs of HIV-1 In Vivo.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 467
Shults K, Derbin D, Flye L, Patterson B; Esoterix Ctr for Innovation, Brentwood, TN
Maximizing the response of specific HIV-1 cellular reservoirs to anti-retroviral therapy is critical for achieving the goal of minimizing or eliminating viral evolution. METHODS: Peripheral blood mononuclear cells from 29 individuals off anti-retroviral therapy were collected and stained with combinations o
468 Monocyte Subsets and HIV Reservoirs in Patients on HAART.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 468
Ellery P, Sonza S, Mills J, Crowe S; Macfarlane Burnet Inst for Med Res and Publ Hlth, Melbourne, Australia
Recent literature describes a minor subset of monocytes characterised by lower CD14 (LPS receptor) and higher CD16 (Fcg receptor III) surface expression than the major monocyte population. Our preliminary data support previous studies that the CD14 lo /CD16 hi subset is significantly expanded in HIV-infecte
469 Immunologic and Virologic Outcome in a Cohort of Long-term Non-progressors After More than 15 Years of HIV-1 Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 469
Rodes B, Toro C, Paxinos E, Fransen S, Wrin T, Bassani S, Poveda E, Soriano V; Inst Salud Carlos III, Madrid, Spain
A cohort of 19 long-term non-progressors (LTNP) was established in 1997. At that time, all had HIV infection proven for at least 10 yrs without antiretroviral therapy, CD4 counts > 500 cells/mm 3 , and lacked HIV-related symptoms. One of them was known to have stored sera already positive for HIV antibodies
470 A Unique Attenuating Deletion in the gp41 Cytoplasmic Domain of the HIV-1 from an Individual With Long-term Non-progressive Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 470
Haran J, Somasundaran M, Sullivan JL, Greenough TC; Univ of Massachusetts Med Sch, Worcester
Viruses from individuals with long-term, non-progressive HIV-1 infection are commonly found to have uniformly persistent, unique, and difficult-to-revert polymorphisms. Sequence analysis of a virus isolated from a remarkable long-term non-progressor showed a truncation involving the last 20 amino acids of t
471 Natural Resistance to Viral Replication in HIV-1 Infected Individuals.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 471
Kloosterboer N, Groeneveld P, Jansen CA, Brinkman K, Winkel CN, Duits AJ, van Baarle D, van Rij RP, Schuitemaker H; Sanquin Res at CLB and Academic Med Ctr, Amsterdam, The Netherlands
During normal HIV infection antibodies against HIV proteins, HIV RNA, and HIV proviral DNA can be found. In this study, we analyzed four HIV-1 infected individuals, who have antibodies against all HIV-1 proteins but who lack any detectable HIV p24 antigen, HIV-1 RNA and HIV-1 proviral DNA. The absence of pr
472 Co-receptor/HLA Class I Genetics and Cellular Immune Response in Patients with a Low Viral Set-point.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 472
Stahmer I, van Lunzen J, Rockstroh J, Fatkenheuer G, Staszewski S, Schneider C, Eiermann T, Tenner-Racz K, Racz P, Stellbrink HJ; Univ Hosp Eppendorf, Hamburg, Germany
To assess the impact of genetic vs immunological factors on control of virus replication in subjects with low viral loads. METHODS: Within a prospective cohort (FITS) of 710 untreated HIV + patients (pts), 34 subjects with viral load set points
473 Dynamic Gene Expression Profiling in Lymphatic Tissues Reveals Prominence of Innate Defenses in Controlling HIV-1 Infection In Vivo and Genes Involved in Inflammation, Tissue Damage, and Repair After Treatment.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 473
Li Q, Schacker T, Carlis J, Beilman G, Nguyen P, Haase AT; Univ of Minnesota Med Sch, Minneapolis
The progression of HIV-1 infection in secondary lymphoid organs, the main site of virus production and storage, is slow, in contrast to the rapid turnover of productively infected cells in vivo and dynamics of infection in vitro. METHODS: To identify host factors that slow the progress of infection in vivo,
474 Global Changes in Gene Expression During HIV Infection and Antiretroviral Therapy.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 474
Dennis G, Yang J, Bosch M, Hosack DA, Sherman BT, Sidorov IA, Dimitrov DS, Adelsberger JW, Metcalf JA, Stevens R, Baseler MW, Davey RT, Polis MA, Lane HC, Lempicki RA; Sci Applications Intl Corp, Frederick, MD
HIV-1 infection is associated with a decline in CD4 + T-cell numbers and a 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 better understand the transcriptional c
475 Modeling of Host Transcription during Acute HIV Infection Using SHIV-infected Cynomolgus Macaques.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 475
Bosinger SE, Cameron MJ, Hosiawa KA, Persad D, Ran L, Rud EW, Kelvin DK; Univ of Western Ontario, London, Canada
HIV modulates the expression of a vast array of host genes that drive pathogenesis. In order to better understand HIV pathogenesis macaques infected with SHIV89.6P were examined during acute infection using high density microarray. Hypothesis: Host expression during the period of severe CD4 + T-cell reducti
475a HIV-1 Induces Human Beta Defensin Expression in Oral Epithelial Cells and Inhibition of HIV-1 Replication In Vitro.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 475a
Quinones-Mateu ME, Lederman MM, Chakraborty B, Feng Z, Marotta ML, Jiang B, Rangel HR, Weber J, Mirza M, Medvick K, Weinberg A; Cleveland Clinic Foundation, Cleveland, OH
Mechanisms of resistance to R5 and X4 HIV-1 infection are incompletely understood. In particular, mechanisms underlying the infrequent transmission of HIV-1 through the oral mucosa are simply unknown. Here we evaluated the anti-HIV-1 activity of human beta defensins (hBDs), small cationic innate defense mol
476 HIV-1 Infection Is Associated with Changes in Drug Transporter Gene Expression In Vivo.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 476
De Pasquale MP, Hulgan T, Sutton L, Carlisle WF, Erdem H, Rueff M, McGowan C, Kim R, Donahue JP, Haas DW, D'Aquila RT; Vanderbilt Univ Med Ctr, Nashville, TN
Drug transporters P-glycoprotein (Pgp) and multi-drug resistance-associated protein 4 (MRP4) efflux protease inhibitors (PI) and nucleoside RT inhibitors (NRTI), respectively. This cross sectional study investigated whether Pgp or MRP4 expression in peripheral blood mononuclear cells (PBMC) in vivo varied b
477 Non-Replicating HIV-1 Virions Induce Increased Expression of Activation Markers in Primary T-cells in a Strain-dependent Manner.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 477
Holm G, Gabuzda D; Dana-Farber Cancer Inst, Boston, MA
During HIV-1 infection, both infected and uninfected CD4 and CD8 T-cells undergo apoptosis, contributing to T-cell depletion. The mechanism for apoptosis of bystander T-cells is controversial. Some groups propose that HIV-1 Env or other stimuli sensitizes T-cells to undergo activation-induced cell death whi
478 HHV-7 Enhancement of HIV Replication in Human Lymphoid Explants.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 478
Duus KM, Zhang Y, Su L, Webster-Cyriaque J; Univ of North Carolina, Chapel Hill
One of the most benign (and thus successful) human pathogens is human herpes virus 7 (HHV-7), a T-cell tropic herpes virus. HHV-7 infects up to 70% of infants prior to the age of 2, and 95% of children have seroconverted by age 5 and often shed the virus asymptomatically via saliva. The absence of HHV-7-med
479
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 477

Abstract not available.
480 SDF-1 Production by Dendritic Cells.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 480
Bermejo M, Pablos JL, Sanchez L, Alcami J; Inst de Salud Carlos III, Madrid, Spain
Emergence of X4 HIV strains occurs late in the course of HIV infection, suggesting that a selective pressure interferes with the switch from CCR5 to CXCR4 coreceptor tropism. We hypothesized that SDF-1 production could be involved in this process, and to this aim we have analyzed the expression of SDF-1 in
481 EBV Infection can Enhance IL-7 Production and Up-regulate the Replication of HIV.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 481
Okamoto Y, Douek D, Russo GB, Koup RA; Vaccine Res Ctr NIH, Bethesda, MD
IL-7 is an epithelial cell-derived lymphoid-specific cytokine known to regulate lymphocyte development and homeostasis. Recent data indicate that plasma IL-7 levels are strongly correlated with T-lymphopenia and viral load and may be associated with disease progression in HIV-infected individuals. Here we e
482 The Two Predominant HIV-1 Variants in Africa, CRF02-AG and Subtype C, Have Different Biological Characteristics.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 482
Bourgeois A, Mpoudi E, Liegeois F, Mognoutou R, Laurent C, Delaporte E, Peeters M; UR36, IRD and Univ of Montpellier, France
Classification of virus isolates as syncytium-inducing (SI) or non-SI (NSI) is considered to be important for the prognosis of disease progression. The appearance of SI variants is related to enhanced CD4 cell depletion and disease progression to AIDS in subtype B infections. Few data exist on the biologica
483 Early Extensive Viremia During SIVmnd-2 Infection in mandrillus sphinx is Associated with Transient Activation of Peripheral and Lymphnode T-cells.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 483
Onanga R, Souquiere S, Makuwa M, Simon F, Barre-Sinoussi F, Muller-Trutwin MC, Roques P; Ctr Intl de Res Med de Franceville, Gabon
The non-pathogenic nature of SIV infection in African non-human primates may be the result of co-evolution of the virus with its respective host. Conversely, cross-transmitted viruses can show increased pathogenicity, as observed for SIVsm/SIVmac in macaques. Mandrills are infected by 2 types of viruses SIV
484 Dysregulation of Chemokine and Dendritic Cell Networks in Lymphoid Tissues during Simian Immunodeficiency Virus Infection In Vivo: Mechanisms of Immunopathogenesis.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 484
Reinhart TA, Fallert BA, Choi YK, Schaefer TM, Sanghavi S, Murphey-Corb MA, Basu S; Univ of Pittsburgh, PA
Chemokines are small chemo-attractant cytokines that mediate cell trafficking during immune inductive and effector activities. Dysregulation of their expression might contribute to the pathogenesis of HIV-1 and the related simian immunodeficiency virus (SIV). Using the SIV/macaque model, we have examined th
485 HIV Superinfection in HIV+ Persons.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 485
Wong T, Kravcik S, Angel J, Gleeson T, Montpetit M; Hlth Canada and Univ Ottawa, Canada
HIV superinfection is the re-infection of an HIV + individual with a new HIV quasi-species. We hypothesized that superinfection is most likely to occur in persons with ongoing risky HIV transmission behaviours. METHODS: We conducted a retrospective cohort study of HIV patients followed for at least 2 yrs at
486 HIV-1 Superinfection with a CRF01_AE Strain: Cell-free RNA Levels are Significantly Lower than the Primary Infecting Subtype B Strain.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 486
Subbarao S, Ramos A, Srinivasan P, Hu D, Vanichseni S, Choopanya K, Chaowanachan T, Tappero J, Mastro T, Folks T; CDC, Atlanta, GA
We have previously described 2 cases of HIV-1 intersubtype superinfection identified from an HIV vaccine preparatory cohort in Bangkok, Thailand . In one case described here, the super-infecting CRF01_AE strain was detected by molecular and serologic analyses approximately 11 months (mos) after complete ser
487 Env is a Cytopathic Determinant of R5-AIDS HIV-1 in SCID-hu Mice.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 487
Olivieri K, Scoggins R, Matthews A, Brodick B, Taylot J, Chernauskas D, Camerini D; Univ of Virginia, Charlottesville
AIDS-associated R5 HIV-1 (R5-AIDS HIV-1) biological clones have greater cytopathic effects (CPE) for CD4 + thymocytes and replicate to higher levels than pre-AIDS R5 biological clones in SCID mice bearing human thymus/liver grafts (SCID-hu mice). We hypothesize that the env and nef genes encode the cytopath
488 Lymphocytes Isolated from Naturally SIV-infected Sooty Mangabeys Do Not Show Signs of Cell-cycle Perturbations or Increased Susceptibility to Apoptosis.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 488
Cervasi B, Paiardini M, Costantino G, Sumpter B, Radziewicz H, McClure H, Magnani M, Piedimonte G, O'Neill S, Staprans S, Feinberg MB, Silvestri G; Emory Univ, Atlanta, GA
The pathogenesis of AIDS is related to both the direct cytopathic effect of HIV on infected CD4 + T-cells and indirect mechanisms of lymphocyte depletion such as increased apoptosis of uninfected T-cells and impaired regeneration of lymphocytes. Naturally SIV-infected sooty mangabeys (SMs) do not progress t
489
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 477

Abstract not available.
490 The Intrinsic Difference in Susceptibility to AIDS-like Disease Induced by Simian Immunodeficiency Virus: Infection of Rhesus Macaques Is Associated with the Ability of Primary CD4+ Lymphocytes to Differentially Control Viral Reverse Transcription.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 490
Hartman A, Rajakumar P, Murphey-Corb M; Univ of Pittsburgh Sch of Med, PA
Rhesus macaques infected with Simian Immunodeficiency Virus (SIV) die of AIDS within an average of 2 yrs; however, survival can vary anywhere from 2 months (mos) to greater than 5 yrs. We have previously shown that PBMC from uninfected animals vary in the ability to produce virus after in vitro infection in
491 Pathogenesis of R5 HIV-1 in Fetal Thymic Organ Culture.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 491
Choudhary S, Kimbrell K, Colasanti J, Chernauskas D, Kwa D, Schuitemaker H, Camerini D; Univ of Virginia, Charlottesville
CCR5 tropic HIV-1 isolates (R5 HIV-1), predominate following transmission and during the clinically latent period of infection. Moreover, R5 HIV-1 strains persist throughout infection and are the only type of HIV-1 found in approximately half of AIDS patients. The pathogenesis of R5 HIV-1 is not well unders
492 Immunological and Virological Failure following Antiretroviral Therapy is Associated with Enhanced Thymic and Peripheral T-cell Pathogenicity.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 492
Solomon A, Cameron P, Bailey M, Dunne A, Crowe S, Hoy J, Lewin S; Univ of Melbourne, Australia
Following antiretroviral therapy (ART) some individuals achieve increases in CD4 T-cells despite persistent viremia. The pathogenesis of this discordant CD4 T-cell response has been explained by reduced thymic pathogenicity of HIV-containing mutations in the protease (PR) gene. If mutations in PR impair CD4
493 Genetic Diversity of HIV-1 Populations in Infected Persons.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 493
Palmer S, Maldarelli F, Kearney M, Kottilil S, Lucey D, Metcalf J, Rock D, VanHoutte M, Michels L, Hertogs K, Mellors J, Coffin J; HIV Drug Resistance Prgm, NCI, NIH, Frederick, MD
Characterization of the genetic diversity of HIV-1 in patients (pts) can provide insight into the mechanism of generation of diversity and resistance. We therefore studied the genetics of a conserved region of the genome using a limiting-dilution RT-PCR technique. METHODS: Plasma samples were obtained from
494 HIV-1 Genetics of Intermittent Low-level Viremia.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 494
Tobin NH, Wang Y, Learn GH, McKernan JL, Ellis GM, Mohan KM, Holte SE, De Vange SM, Pawluk DM, Melvin AJ, Lewis PL, Beck IA, Mahalanabis M, Mullins JI, Frenkel LM; Univ of Washington, Seattle
The causes and results of intermittent low-level viremia (50-500 copies/ml) during HAART are not well understood. We address these issues using viral genetic analysis in the evaluation of children with viremia blips while on HAART. METHODS: Regions of pol encoding PR and RT and env (C2-V5 region) were ampli
495 Early HIV-1 Viral Diversity Associated with Rapid Disease Progression.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 495
Gottlieb GS, Jensen MA, Nickle DC, Wong KG, Li F, Learn GH, Margolick JB, Mullins JI; Univ of Washington, Seattle
The high levels of global and intra-patient viral diversity observed in HIV infection are a direct consequence of the rapid turnover and high mutation rates intrinsic to the virus, as well as selective forces encountered within the host. How this extensive viral diversity impacts HIV disease progression is
496 Low Pretreatment Diversity of HIV-envelope Sequences in Chronically Infected Patients Predict Spontaneous Control of Plasma Viremia after Structured Treatment Interruptions.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 496
Joos B, Fischer M, Kuster H, Leemann C, Boni J, Oxenius A, Wong J, Price D, Phillips R, Hirschel B, Weber R, Trkola A, Gunthard H; Univ Hosp, Zurich, Switzerland
It is under debate whether HIV-disease progresses more rapidly in patients (pts) harboring viruses with low- or with high-viral diversity. For this reason, we studied plasma HIV-env diversity in HIV-infected pts prior to long-term combination antiretroviral therapy (ART). We then tested whether pretreatment
497 Maintenance of the Complexity of the env Gene Populations during Fixation of a Drug Resistance Marker at High but Not Low HIV-1 RNA Load: A Potential Role for Recombination.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 497
Kitrinos KM, Nelson JA, Resch W, Swanstrom R; Univ of North Carolina, Chapel Hill
The initiation of drug therapy can result in a reduction of virus load, causing a contraction in the virus population. This contraction represents a potential genetic bottleneck for HIV-1. While the bottleneck directly affects the gene targeted by the drug, it may also have an impact on other regions. We ha
498 A Bioinformatic Predictor of Coreceptor Usage Correlates with Markers of Disease Progression and Supports the Gradual Evolution of X4 Virus via R5X4 Intermediates.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 498
Jensen M, Gottlieb G, van 't Wout A, Li FS, Nickle D, Shriner D, Wong K, He HX, McLaughlin S, Shankarappa R, Margolick J, Mullins J; Univ of Washington, Seattle
HIV in primary infection is usually R5 in phenotype, e.g., it uses only CCR5 as a co-receptor. Often, the virus undergoes a genetic shift, leading to the outgrowth of CXCR4-using X4 virus, associated with increased pathogenicity and faster disease progression. We previously validated a bioinformatic predict
499 Compartment-specific Patterns Associated with CSF-derived V3 Sequences.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 499
Good B, Pillai S, Corbeil J, Wong J; Veterans Med Res Fndn, San Diego, CA
It has been hypothesized that the selective environment within the CNS compartment differs from that of peripheral tissues. Therefore, it is expected that virus replicating within the CNS should develop distinct genotypic and phenotypic characteristics from peripheral virus. V3 genotype is likely to differ,
500 High Diversity of Cell-associated Reservoirs of HIV-1 May Contribute to Viral Genetic Shifts in the Plasma.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 500
Liegler T, Harris J, Warmerdam M, Barbour J, Montaner LJ, McCune JM, Grant RM; J D Gladstone Inst of Virology and Immunology, San Francisco, CA
Viral variants that appear in blood plasma during STI are not always representative of those isolated from peripheral blood cells. We hypothesized that genetic diversity in replication-competent HIV-1 populations associated with blood cells is high, thereby requiring multiple isolates for characterization.
501 SIVcpz Prevalence and Genetic Diversity in Wild Communities of Eastern Chimpanzees.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 501
Santiago M, Lukasik M, Kamenya S, Li Y, Bibollet-Ruche F, Goldenberg D, Muller M, Emery M, Watts D, Wrangham R, Pusey A, Collins D, Goodall J, Shaw G, Hahn B; Univ of Alabama at Birmingham
Current knowledge of the prevalence and genetic diversity of simian immunodeficiency virus (SIVcpz) infection of wild chimpanzees (Pan troglodytes) is incomplete since only few isolates have been characterized; yet this information is critical for understanding the origins of HIV-1 and the circumstances lea
502 Antiretroviral Resistance Among Patients with Primary HIV Infection in the Southeastern U.S.-Impact on Treatment Outcome.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 502
Hicks C, Eron J, Lennox J, Pilcher C, Fiscus S, Weintrob A, Giner J, Menezes P, Patrick E, Alcorn T; Duke Univ Med Ctr, Durham, NC
The frequency of transmission of antiretroviral resistance in primary HIV infection (PHI) patients (pts) varies among different geographic regions. The clinical significance of such resistance is also incompletely defined. We assessed baseline (BL) genotypic and phenotypic resistance and its consequences in
503 Replication Characteristics of Drug-resistant and Drug-susceptible HIV-1 Variants Isolated during Primary Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 503
Simon V, Padte N, Vanderhoeven J, Murray D, Mascio MD, Markowitz M; Aaron Diamond AIDS Res Ctr, Rockefeller Univ, New York, NY
Drug-resistant HIV-1 variants generally display reduced replication capacity compared to drug susceptible viruses. Drug-resistant isolates derived from individuals during primary infection might display different properties since replication capacity is thought to be an important determinant for transmissio
504 Frequency of Transmitted Drug Resistance and Identification of Phylogenetic Clusters in a Homogenous Cohort of Newly Infected Individuals.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 504
Simon V, Hogan C, Louie M, Vasan S, Rowe L, Hurley A, Padte N, Vanderhoeven J, Dawson K, Balfe P, Markowitz M; Aaron Diamond AIDS Res Ctr, Rockefeller Univ, New York, NY
The frequency of transmitted drug resistant HIV-1 has varied in recent years. In addition, the degree to which these viruses are related has remained unexplored. METHODS: Baseline samples from 85 newly HIV-1 infected individuals (NI) identified in 2001-2002 were analyzed by sequencing (TruGene) and by drug
505 The Relative Transmissibility of Drug Resistant HIV-1 among Couples.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 505
Grant RM, Atchison R, Franses K, Rollins A, Warmerdam M, Kahn JO, Hecht FM; Gladstone Inst of Virology and Immunology, San Francisco, CA
Case series indicate that drug resistant HIV-1 can be transmitted, although the relative transmissibility is unknown. Partner studies directly assess the transmission of drug resistant viral mutants after well-characterized exposure. METHODS: The Options project evaluated persons who were recently exposed t
506 Pre-Exisiting HIV-specific CD8+ CTL Fail to Prevent HIV Infection in an HIV Sero-discordant Couple.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 506
Fidler S, Pinheiro S, Nicholson C, Dong T, Zhang HT, Clarke J, Phillips R, Rowland-Jones S, Weber J; Imperial Coll, London, UK
Despite repeated exposure to HIV-1, rare subjects persistently fail to become infected. Resistance to HIV maybe associated with HIV-specific CD8 + cytotoxic lymphocyte (CTL) responses. Therefore, HIV vaccine development has aimed at generating high frequency HIV-specific CD8 + CTLs. STUDY DESIGN: Longitudin
507 Evaluation of HLA Class II DRB1 and DQB1 Genotypes in Discordant Zambian Couples at Risk of Heterosexual HIV-1 Transmission.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 507
Tanga J, Penman-Aguilar A, Lobashevsky E, Zulu I, Allen S, Aldrovandi G, Kaslow RA; Univ of Alabama, Birmingham
Heterosexual transmission of HIV-1 predominates in sub-Saharan Africa. Objective: To identify immunogenetic determinants of viral transmission in a cohort of native Africans. METHODS: Cohabiting, HIV-1-discordant Zambian couples were enrolled for a longitudinal study between 1995-2002. Documented transmissi
508 Virus Load in HIV-1 Seroconverters Who Share HLA Class I and Class II Alleles with Their Respective Transmitting Partners.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 508
Tang J, Tang S, Lobashevsky E, Zulu I, Aldrovandi G, Allen S, Kaslow RA; Univ of Alabama at Birmingham
HIV-1 viruses readily evolve in response to host immunity. More rapid adaptation of the virus presumably accounts for the documented increased likelihood of viral transmission from a seropositive (index) to a seronegative (recipient) sexual partner in the presence of greater HLA allele concordance. We searc
509 Defining the 'Viral Setpoint' in HIV-1 Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 509
Frost SD, Holte S, Wang L, Daar ES, Richman DD, Little SJ; Univ of California at San Diego
Viral setpoint is a term used to describe the quasi-steady viral load during the asymptomatic period of HIV-1 infection with high setpoints correlated with rapid disease progression, high infectiousness, and poorer responses to treatment. Previous studies have used different ad hoc definitions of setpoint b
510 Influence of HLA-B57 on Clinical Presentation and Viral Control during Acute HIV-1 Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 510
Altfeld M, Addo MM, Rosenberg ES, Hecht FM, Lee PK, Vogel M, Draenert R, Yu XG, Johnston MN, Allen TM, Sekaly RP, Levy JA, Rockstroh JK, Goulder PJ, Walker BD; Massachusetts General Hosp, Boston
HLA-B57, as well as CTL responses restricted by this allele, have been strongly associated with long-term, non-progressive HIV-1 infection. However, their impact on viral replication during acute HIV-1 infection is not understood. In this study, we assessed clinical and immunological parameters during acute
511 The Role of Target Cells and Specific Immunity in Primary SIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 511
Regoes RR, Antia R, Garber D, Silvestri G, Feinberg MB, Staprans SI; Emory Univ, Atlanta GA
The virus load shortly after the primary infection is one of the best correlates of disease progression. Therefore, an understanding of the factors governing primary HIV infection is crucial for the design of rational treatment and vaccination strategies. Two main hypotheses of the driving force of primary
512 Structured Treatment Interruptions in Acute HIV Seroconverters: Preliminary Results of the Multicenter Prospective PRIMSTOP Pilot Trial (ANRS 100).
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 512
B. Hoen1, C. Lacabaratz2, I. Fournier3, I. Charreau3, M. Burgard4, F. Raffi5, P. Morlat6, T. May7, J. P. Aboulker3, A. Venet2, C. Rouzioux4, Primstop Study Group
Although viral rebound at wk 2 post-STI tended to decrease from 1st to 3rd STI, maximum viral rebound within each STI did not. So far, persistent control of HIV replication after cessation of a 2-year HAART/STI regimen was observed in a small minority of pts.
513 Predictors of Plasma HIV RNA Control after Discontinuation of HAART Initiated at Acute Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 513
A. Lafeuillade1, E. Counillon2, C. Poggi1, G. Hittinger1, D. Emilie3
In this series, the multivariate analysis identified a low proviral DNA level in PBMC at M24 and a strong proliferative response against p24 as independant predictors of viral control after cessation of therapy initiated at acute infection.
514 The Early Effect of Highly Active Antiretroviral Therapy During Acute Retroviral Syndrome is Associated with the Time of Starting and the Duration of Symptoms.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 514
Vanhems P, Voirin N, Routy JP, Baratin D, Legault M, Trepo C, Miaihles P, Boulassel MR, Livrozet JM, Touraine JL, Fabry J; Edouard Herriot Hosp and INSERM U271, Lyon, France
Background. Highly active antiretroviral therapy (HAART) during acute retroviral syndrome (ARS) provides effective suppression of HIV replication and may limits escape mutations. The time to initiate HAART during ARS is not clearly established. We explored the early effect of HAART on plasma HIV viral load (VL) and CD4
515 T-cell Subset Perturbations During the First Interruption Phase of Subjects Treated During Primary HIV Infection: Activation and CCR5 Expression Correlate with Viral Load.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 515
Zaunders J, Munier M, Cunningham P, Smith D, Grey P, Quan D, McFarlane R, Kelleher A, Cooper DA; St Vincent's Hosp, Sydney, Australia
Changes in CD4 and CD8 T-cell subsets during primary HIV infection (PHI) have been inferred from cross-sectional studies of symptomatic subjects at presentation. However, little is known about events in the very early period leading up to onset of symptoms. Prospective study of changes occurring during inte
516 Analysis of Treatment-associated Viral Load Change During Primary HIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 516
Grey P, Johnston M, Petoumenos K, Ramacciotti T, Cunningham P, Rosenberg E, Smith D, Robbins G, Finlayson R, Cooper D, Walker B, Kaldor J, Corcoran C, Carr A; Univ of New South Wales, Sydney, Australia
Primary HIV Infection (PHI) is often associated with high viral loads and transient CD4 decline, which may influence time to achieving an undetectable viral load on therapy. Therefore, we looked at what may be the determinants of viral suppression with treatment of PHI. METHODS: Both acute and early PHI pat
517 Impact of Therapeutic Interruptions in Patients Treated during Primary Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 517
C. Goujard1, C. Deveau2, M. Sinet3, C. Jacomet4, C. Lascoux5, T. Allegre6, H. Bazin7, C. Rouzioux8, J. F. Delfraissy1, L. Meyer2
Our results suggest that subject characteristics at the time of treatment initiation during primary infection, but not the duration of the treatment or the duration of the virological control, are associated with plasma viral load levels during treatment interruption. Although median viral load after treatment interruption was similar to that observed during natural history, there was a huge heterogeneity: 4 pts controlled their viremia after an interruption of more than 18 months.
518 CD4 Activation Predicts Virologic Failure in HAART for Primary HIV.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 518
Hecht FM, Gascon R, Liu L, Deeks S, Kahn J, Chesney M, Grant R, Busch M, McGrath M; Univ of California at San Francisco
The objective of this study was to assess the role of immune activation, after controlling for virologic factors and adherence, in predicting failure of HAART in persons with primary/early HIV infection (P/EHI). METHODS: We assessed persons in the UCSF Options cohort who started HAART within 12 months of HI
519 Is HAART for Primary/Early HIV Infection Associated with Improved Outcomes After Treatment Discontinuation?
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 519
F. M. Hecht1, L. Wang2, A. Collier3, J. Margolick4, S. Little5, M. Kilby6, C. Benson7, B. Conway8, E. Daar9, M. Markowitz10, S. Holte2
After controlling for baseline differences, the data suggest treating very early HIV was associated with lower VL and higher CD4 counts 24 wks after stopping treatment. However, the lack of clear benefit in unadjusted analyses and limitations of statistical adjustments to compensate for baseline differences suggest that randomized controlled trials would be useful to definitively assess the role of treatment in primary HIV infection.
520 The QUEST Cohort: Treatment of Primary HIV Infection with Quadruple HAART: Week 48 Preliminary Results.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 520
Kinloch S, Cooper D, Lampe F, Smith D, Janossy G, Hoen B, Sonnerborg A, Tsoukas C, Phillips A, Goh L, Perrin L; Royal Free Hosp and Univ Coll, London, UK
In the Quest study, primary HIV infection (PHI) patients (pts) initiate HAART for 3 18 months (mos), followed by randomization to 6 mos of HAART ± vaccine(s) before stopping treatment. This analysis describes treatment continuation rates and virological and immunological changes during the first 48 weeks
521 Viral Blips During HAART in Primary HIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 521
Mascio MD, Markowitz M, Louie M, Hogan C, Simon V, Hurley A, Ho DD, Perelson AS; Los Alamos Natl Lab, NM
We previously reported that chronically HIV-1 infected patients (pts) have a higher tendency to show viral blips during HAART than pts treated during acute and early HIV infection (PHI), with this tendency being independent of the drug regimen. METHODS: We analyzed 68 pts in 6 prospective studies [LPV/RIT/T
522 Impact of MDR1 (C3435T) Genetic Polymorphism in Patients Naive Treated with HAART including Indinavir.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 522
Verstuyft C, Marcellin F, Morand-Joubert L, Launay O, Peytavin G, Gerard L, Becquemont L, Aboulker JP; St Antoine Hosp, Paris, France
Abstract not available.
523 MDR-1 Genetic Polymorphism Does Not Influence the Response to Antiretroviral Therapy with Protease Inhibitors in Drug-naïve Patients with HIV Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 523
Nasi M, Borghi V, Pinti M, Bellodi C, Lugli E, Mussini C, Esposito R, Cossarizza A; Univ of Modena, Italy
P-glycoprotein (P-gp) is a membrane-localized transporter, codified by the gene MDR1, that pumps out from cells several drugs, including HIV- protease inhibitors (PI). A polymorphism exists in exon 26 (C3435T) that can influence the response to PI or non-nucleosidic reverse transcriptase inhibitors (NNRTI).
524 Regulation and Effects of T-lymphocyte P-glycoprotein Activity during HIV-1 Infection.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 524
Hulgan T, Donahue JP, Hawkins C, D'Aquila RT, Nicotera F, Rebeiro P, Rueff M, Erdem H, Unutmaz D, Haas DW; Vanderbilt Univ Sch of Med, Nashville, TN
The efflux pump P-glycoprotein (P-gp) decreases disposition of HIV protease inhibitors (PI) into selected cells. Causes and effects of variable lymphocyte P-gp activity are uncertain. We are studying a cohort of HIV-infected adults to identify pharmacologic, viral, and host factors regulating P-gp activity.
524a The Effect of ABCB1 (MDR1) Polymorphism on the Plasma and Intracellular Pharmacokinetics of Indinavir and Glucose Handling in Healthy Volunteers.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 524a
Maher B, Hoggard PG, Chandler B, Meaden ER, Owen A, Back DJ, Khoo SH, Pirmohamed M; Univ of Liverpool, Liverpool, UK
Use of Protease Inhibitors (PIs) is associated with dyslipidaemia and insulin resistance; these are observed even with short-term use of PIs. Since transport by drug efflux pumps such as P-glycoprotein (P-gp) influences the disposition of PIs, we have investigated indinavir
525 Lopinavir Drug Levels Predict the Virological and Immunological Outcome as well as Lipid Elevations.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 525
Gonzalez de Requena D, Gallego O, Blanco F, Valer L, Garcia-Benayas T, Mendoza CD, Jimenez-Nacher I, Soriano V; Hosp Carlos III, Madrid, Spain
Introduction: Response to Kaletra (LVP/r) based salvage regimens may be influenced by both the number of mutations at the protease and LPV plasma levels. Moreover, cholesterol (CHOL) and triglyceride (TG) levels may be related to LPV levels. METHODS: All HIV + patients (pts) with prior exposure to antiretrovi
526 Relation between Lopinavir Plasma Blood Concentrations and Hypertriglyceridemia in Naive and Protease Inhibitors-experienced Patients.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 526
Calboreanu A, Dimet J, Treluyer JM, Abad S, Pecqueux L, Krivine A, Sicard D, Salmon-Ceron D; Internal Med Dept, Cochin Hosp, Paris, France
In HAART treated patients (pts), a correlation has been found between plasma blood levels of several protease inhibitors (PI) and the occurrence of their side effects. Objective: To evaluate whether there is a relationship between lopinavir (LPV) plasma concentrations and the occurr
527 Population Pharmacokinetics of Lopinavir/Ritonavir in Experienced Patients.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 527
Best B, Haubrich R, Miller C, Witt M, Kemper C, Squires K, Diamond C, Heseltine P, Hellmann N, McCutchan JA, Capparelli E; Univ of California at San Diego
Published lopinavir (LPV) pharmacokinetic data, generated in treatment naïve patients (pts), may not adequately reflect LPV pharmacokinetics and its clinical variability. Our objective was to describe the pharmacokinetics of LPV at steady-state in treatment-experienced pts with population methods, and to re
528 Correlation of Viral Load Reduction and Plasma Levels in Multiple Protease Inhibitor Experienced Patients Taking Tipranavir/Ritonavir in a Phase IIB Trial: BI 1182.52.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 528
Yeni P, MacGregor T, Gathe J, Arasteh K, Jayaweera D, Jemsek J, Hawkins T, Cameron W, Bodsworth N, McCallister S, Kohlbrenner V, Quinson A, Leith J, Sabo J, Mayers D; Groupe Hosp Bichat-Claude Bernard, Paris, France
Tipranavir (TPV)-based therapy, has demonstrated a uniquely robust resistance profile with sustained viral load response during up to 48 wks of treatment in single and multiple Protease Inhibitor (PI)-experienced patients (pts). The preliminary target median plasma concentration for TPV has been set at 10X
529 Are Random Antiretroviral Drug Levels Associated with Objectively Measured Adherence Behavior?
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 529
C. Liechty1, C. Alexander2, R. Harrigan2, D. Guzman1, E. D. Charlebois1, A. R. Moss1, D. R. Bangsberg1
We found that a single abnormally low random drug level can predict adherence below 90%, but normal levels do not reliably indicate adherence above this threshold. This relationship is strong for all drugs studied except indinavir.
530 Differential Phosphorylation of Zidovudine and Lamivudine Between Semen and Blood Mononuclear Cells in HIV-1 Infected Men.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 530
Reddy S, Troiani L, Kim J, Rodriguez J, Fiscus S, Kempen AV, Cohen M, Kashuba A; Univ of North Carolina, Chapel Hill
Therapeutic concentrations of ARVs into the male genital tract may reduce viral replication and influence selection and transmission of resistant HIV-1 variants. We have previously reported that Zidovudine and Lamivudine (ZDV/ 3TC ) semina
531 Lopinavir/Ritonavir Combined with Twice-daily Indinavir: Pharmacokinetics in Blood, CSF, and Semen (The Protect Study).
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 531
Isaac A, Taylor S, Rubin G, Gibbon S, White D, Drake S, Back D; Birmingham Heartlands Hosp, UK
Combination therapy including 3 protease inhibitors may be an option for drug-experienced patients. However, drug interactions can lead to toxicities or sub-therapeutic drug concentrations. We hypothesised that adding indinavir (IDV) 400 mg BD to
532 Antiretroviral Proficiency Testing Program for the Adult AIDS Clinical Trials Group (AACTG) Pharmacology Laboratory Network.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 532
Holland D, DiFrancesco R, Hamzeh F, Morse GD; Univ of California at San Diego
The AACTG Pharmacology Laboratory Network has implemented a comprehensive quality assurance program including assay validation procedures, quality control monitoring and a proficiency testing program. Proficiency testing includes both adult (n = 6) and pediatric (n = 5) pharmacology laboratories. METHODS: T
533 Didanosine and Tenofovir DF Drug-drug Interaction: Assessment of Didanosine Dose Reduction.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 533
Kearney BP, Isaacson E, Sayre J, Namini H, Cheng A; Gilead Sci, Inc, Foster City, CA
Previous PK studies have identified increased drug exposure when didanosine (ddI) buffered tablet or enteric-coated capsule formulations are co-administered with tenofovir DF (TDF). These increases are such that ddI dose reduction may be appropriate to reduce the risk for ddI-associated adverse events.
534 Lack of Interaction between Stavudine Extended-release Formulation and Tenofovir Disoproxil Fumarate.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 534
Kaul S, Bassi K, Damle B, Smith R, Gale J, O'Mara E, Chaudhari U, Ryan K; Bristol-Myers Squibb Pharm Res Inst (BMSPRI), Princeton, NJ
A once daily formulation of stavudine ( d4T XR) was developed to simplify HIV treatment. This study was designed to investigate the effect of d4T XR and
535 A Two-way Drug Interaction Between Lopinavir/Ritonavir and Phenytoin.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 535
Lim ML, Min SS, Eron JJ, Bertz R, Robinson M, Gaedigk A, Kashuba AD; Univ of North Carolina, Chapel Hill
Lopinavir/ Ritonavir (LPV/r) inhibits CYP3A4 and Phenytoin (PHT) is a substrate for CYP2C9 and CYP2C19; both drugs are CYP450-inducers. The purpose of this study was to assess the multiple-dose pharmacokinetic (PK) interaction between LPV/r and PHT. METHODS: An open-label, randomized, 2-period crossover, st
536 Assessment of the Multiple-dose Pharmacokinetic Interaction of Lopinavir/Ritonavir with Nelfinavir.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 536
Klein C, Bertz R, Ashbrenner E, Chira T, Williams L, Hsu A, Bernstein B; Abbott Labs, Abbott Park, IL
The HIV PIs nelfinavir (NFV) and lopinavir / ritonavir (LPV/r) are substrates for and inhibitors of CYP3A, as well as metabolic inducers. The purpose was to assess the effects of co-administration of LPV/r and NFV on pharmacokinetic parameters of LPV, ritonavir (RTV), NFV, and the h
537 Pharmacokinetic Parameters of Atazanavir/Ritonavir when Combined to Tenofovir in HIV Infected Patients with Multiple Treatment Failures: A Sub-study of Puzzle2-ANRS 107 Trial.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 537
A. M. Taburet1, C. Piketty2, L. Gérard3, I. Vincent1, C. Chazallon3, F. Clavel4, V. Calvez5, J. P. Aboulker3, P.M Girard6
At wk 2, ATV pk parameters when combined with RTV are in agreement with data obtained in healthy volunteers. After TDF introduction, both ATV and RTV parameters seemed to be reduced. These preliminary findings suggest that decrease in ATV concentrations at wk 6 could result from lowered RTV concentrations, even though the differences on most parameters did not reach statistical significance. The impact of TDF on ATV pk when given alone is unknown. Mechanism of this interaction, likely to occur at the absorption level, needs further investigation.
538 Pharmacokinetics and Pharmacodynamics of Low-dose Mycophenolate Mofetil in Early Stage HIV-infected Patients Successfully Treated with HAART.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 538
Martorell J, Brunet M, Garcia F, Mestre G, Plana M, Libois A, Gallart T, Pumarola T, Miro J, Blanco JL, Martinez E, Mallolas J, Lange J, Pantaleo G, Gatell JM; Inst d'Investigacions Biomediques August Pi i Sunyer, Hosp Clin, Univ of Barcelona, Spain
Mycophenolate mofetil, has been proposed to potentiate the inhibition of human immunodeficiency virus (HIV) replication mediated by some antiretroviral agents. We compare pharmacokinetic and pharmacodynamic of two doses 0.25 g BID and 0.5 g BID. METHODS: MPA plasma levels (HPLC), and the capacity of patient
539 Mycophenolate Mofetil Lowers Plasma Nevirapine Concentrations but Has No Effect on Intracellular Triphosphate Concentrations.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 539
Sankatsing S, Hoggard P, Back D, Kewn S, Huitema A, Crommentuyn K, Beijnen J, Lange J, Prins J; Intl Antiviral Therapy Evaluation Ctr, Amsterdam, The Netherlands
Recent studies suggest a potential role for mycophenolate mofetil (MMF) in the treatment of HIV-1. MMF interferes with cellular guanosine nucleotide biosynthesis, thereby limiting lymphocyte proliferation. This might limit the availability of target cells for HIV-1 infection. In vitro MMF has a direct anti
540 Two-year Evaluation of the Interactions between Antiretroviral Medication and Cyclosporine in HIV+ Liver and Kidney Transplant Recipients.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 540
Frassetto LA, Baloum M, Roland ME, Carlson L, Stock P, Benet LZ; Univ of California at San Francisco
Solid organ transplantation in HIV + patients (pts) is complicated by the interactions between antiviral therapy (ARV) and immunosuppressive agents, e.g., cyclosporine (CsA). High drug levels could result in increased toxicity; low levels could result in organ rejection or HIV viral breakthrough. Pharmacoki
541 Enfuvirtide: Investigations on the Drug Interaction Potential in HIV-infected Patients.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 541
M. Boyd1, K. Ruxrungtham1, X. Zhang2, E. Bellibas2, N. E. Buss3, I. H. Patel2
Co-administration of ENF with SQV/r, RTV, or rifampicin did not lead to a clinically relevant interaction and was well tolerated over the duration of the studies. Consistent with the expectations of a peptide drug, low potential for drug-drug interaction is confirmed for ENF by these investigations.
542 Pharmacokinetic Interaction between Rifampin and the Twice-daily Combination of Indinavir and Low-dose Ritonavir in HIV-infected Patients.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 542
Justesen U, Andersen A, Klitgaard N, Brosen K, Gerstoft J, Pedersen C; Univ of Southern Denmark, Odense, Denmark
Indinavir (IDV) is primarily metabolized by cytochrome P450 (CYP) 3A4. Rifampin is known to be a strong inducer of CYP3A4, which makes treatment of tuberculosis in HIV-infected patients (
543 Atazanavir: A Summary of Two Pharmacokinetic Drug Interaction Studies in Healthy Subjects.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 543
Tackett D, Child M, Agarwala S, Geiger M, Geraldes M, Laura B, O'Mara E; Bristol-Myers Squibb Pharm Res Inst, Princeton, NJ
Atazanavir (ATV) is a potent, safe, and effective once-daily (QD) azapeptide protease inhibitor (PI) currently in Phase III development. Two individual pharmacokinetic (PK) drug interaction studies were conducted. The first study was conducted to assess whether efavirenz (EFV),
544 Pharmacokinetics of Nelfinavir (Viracept 250 mg tablet): Effect of Food Intake on Single-dose PK Parameters.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 544
Petersen C, Pun E, Strada R, Daniels E, Bramson C, Randinitis E; Agouron Pharmaceuticals, Inc, a Pfizer Co, La Jolla, CA
Highly active antiretroviral therapy has led to markedly improved survival and decreased disease related morbidity in HIV + individuals. Current efforts to improve therapy include optimizing the use of established agents, identifying new agents and new classes of drugs and decreasing the side effects of t
545 The Effect of Ethanol on Protease Inhibitor Exposure in Chronic Heavy Ethanol Users.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 545
Aweeka F, Lizak P, Karan L, Kosel B, Au S, Weiner M, Lu M; Univ of California at San Francisco
The effect of ethanol on the pharmacokinetics (PK) of drugs has not been fully investigated. Of HIV-infected subjects, 25% are heavy drinkers and susceptible to drug-drug interactions between ethanol and antiretroviral therapy. Ethanol may induce cytochrome p450 (CYP) metabolism when used chronically. Howev
546 High Indinavir Plasma Concentrations in HIV-1 Patients Co-infected with Hepatitis B or C Virus Receiving Indinavir and Ritonavir Low Dosages: A GENOPHAR Substudy.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 546
Bossi P, Peytavin G, Lamotte C, Ait-Mohand H, Bonmarchand M, Ktorza N, Simon A, Delagerre C, Calvez V, Bricaire F, Costagliola D, Katlama C; Pitie-Salpetriere Hosp, Paris, France
To evaluate the efficacy and safety of the combination of indinavir / ritonavir (IDV/RTV) low dose (400/100 mg bid) with two NRTI in patients (pts) with chronic HepatitisC (HCV) or Hepatitis B (HBV). METHODS: We have analyzed this combination in pts co-inf
546A The Preclinical Pharmacokinetics and Safety Pharmacology of the Anti-HIV CCR5 Antagonist, UK-427, 857.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 546-A
Napier C, Dorr P, Gladue R, Halliday R, Leishman D, Machin I, Mitchell R, Nedderman A, Perros M, Roffey S, Walker D, Webster R; Pfizer Global R&D, Sandwich Labs, Kent, UK
Abstract not available.
547 Pharmacokinetics of Single and Multiple Oral Doses of UK-427,857-A Novel CCR5 Antagonist in Healthy Volunteers.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 547
Abel S, Van der Ryst E, Muirhead GJ, Rosario M, Edgington A, Weissgerber G; Pfizer Global Research and Dev, Sandwich Labs, Kent, UK
UK-427,857, an antagonist of the CCR5 receptor with potent anti-HIV activity in vitro, is being developed for the treatment of HIV infection. Studies in healthy volunteers were conducted to evaluate the pharmacokinetics, safety and toleration of the compound. METHODS: Healthy male volunteers received single
548
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 548

Abstract not available.
549 TMC114, A Next Generation HIV Protease Inhibitor: Pharmacokinetics and Safety Following Oral Administration of Multiple Doses With and Without Low Doses of Ritonavir in Healthy Volunteers.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 549
Hoetelmans R, Van der Sandt I, Pauw MD, Struble K, Peeters M, Van der Geest R; Tibotec, Mechelen, Belgium
TMC114 is a next generation protease inhibitor (PI) with potent in vitro antiviral activity against wild-type and PI-resistant HIV-1. The objective of the study was to evaluate the pharmacokinetics (PK) and safety/tolerability of TMC114 with and without low doses of ritonavir
549a Quality-Control Analysis of Generic Nevirapine Formulations in the Developing World: An Initial Report.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 549a
Penzak S, Tavel J, Acosta E, Turner M, Masur H; Clin Ctr, NIH, Bethesda, MD
To our knowledge, this data represents the first publicly available account of drug content among generic ARV preparations. The results are encouraging and consistent with stringent manufacturing standards ( é 3% of labeled drug amount). These data are reassuring given the widespread use of NVP-containing products in the developing world. Quality assurance analyses such as this one, must be conducted on a large-scale basis and include all generically available ARVs. When this information is available, health care providers and governmental agencies can determine which ARV formulations are most likely to provide HIV-infected patients in the developing world with the greatest possibility for clinical benefit.
550 Long-term Efficacy and Safety of Emtricitabine in HIV+ Adults Switching from a Lamivudine Containing HAART Regimen.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 550
Wakeford C, Shen G, Hulett L, Quinn JB, Rousseau F; Triangle Pharm, Inc, Durham, NC
Emtricitabine (Coviracil, FTC) is a cytosine analog that has demonstrated superior antiviral activity and safety compared to stavudine in a randomized, double-blind clinical trial. FTC-303 was a randomized, 48-week (wk), open label equivalence trial in which patients (pts) with HIV-1 RNA &#8804; 400 cop
551 Once-daily Combination of Emtricitabine, Didanosine, and Efavirenz vs Continued PI-based HAART in HIV-infected Adults with Undetectable Plasma HIV-RNA: 48-week Results of a Prospective Randomized Multicenter Trial (ALIZE-ANRS 99).
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 551
J M Molina1, F Ferchal1, C Rancinan2, P Yeni3, W Rozenbaum4, V Journot2, L Morand-Joubert5, S Fournier1, P Morlat 6, B Dupont 7, JF Delfraissy8, P Dellamonica9, I Poizot-Martin10, E Rosenthal9, G Chene2
The substitution of a PI-based regimen by a simple once-daily combination of emtricitabine, didanosine, and efavirenz maintained full control of plasma HIV-RNA levels and continued increases in CD4 counts for 48 wks.
552 Sustained Anti-HIV-1 Effect of Racivir Combined with D4T and Sustiva Following a 14-day Treatment of Infected Volunteers.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 552
Otto MJ, Arasteh K, Kreckel P, Drauz D, Beard A, Cartee L, Hurwitz SJ, Liotta DC, Schinazi RF, Murphy RL; Pharmasset, Inc, Tucker, GA
Racivir (RCV, [±]-2-hydroxymethyl-5-[5-fluorocytosine-1-yl]-1,3-oxathiolane) is a nucleoside analog with potent and selective activity against both HIV and HBV in cell culture and in animal models. It is well tolerated in preclinical safety assessment studies in dogs (> 100 mg/kg/day for 28 days) and rat
553 TMC114 (UIC96017): A Novel Nonpeptidic Protease Inhibitor Potent Against Multi-PI Resistant HIV In Vitro.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 553
Koh Y, Nakata H, Maeda K, Kincaid JF, Bilcer G, Thippeswamy D, Ghosh AK, Mitsuya H; Kumamoto Univ Sch of Med, Japan
The rapid rise of multi-protease inhibitor (PI)-resistant HIV variants urges the development of new classes of PIs which are potent against existing resistant HIV variants and do not allow or delay the emergence of resistance. We designed, synthesized, and identified TMC114 (UIC96017), a novel non-peptidic
554 Preliminary Results of Dosing of Amdoxovir in Treatment-experienced Patients.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 554
Thompson M, Richmond G, Kessler H, Bae A, Sorbel J, Sista N, Adda N, Rousseau F; Atlanta, GA
Amdoxovir (DAPD), a dioxalane guanosine analog, and its deaminated metabolite DXG are nucleoside reverse transcriptase inhibitors (NRTIs). DAPD 150 is a 96-week study designed to evaluate the long-term safety, tolerability, and antiviral activity of DAPD. METHODS: In an on-going nonrandomized, open-label, P
555 Long-term Efficacy and Safety of Atazanavir with Stavudine and Lamivudine in Patients Previously Treated With Nelfinavir or ATV: 108-week Results of BMS Study 008/044.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 555
Murphy R, Pokrovsky V, Rozenbaum W, Wood R, Percival L, Odeshoo L, Giordano M; Northwestern Univ, Chicago, IL
Atazanavir (ATV) is a potent, safe, well-tolerated, once-daily azapeptide protease inhibitor (PI) in Phase III development that does not result in clinically relevant elevations in serum lipids. The objectives of the Phase II trial BMS AI424-044 are to assess the long-term efficacy and safety of ATV beyond
556 Distinct Antiviral Resistance Profiles for the Authentic HIV Integrase Inhibitors; the Diketo Compounds L-708,906 and S-1360 and the Pyranodipyrimidine V-165.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 556
Fikkert V, Maele BV, Remoortel BV, Michiels M, Vercammen J, Pannecouque C, Engelborghs Y, Clercq ED, Debyser Z, Witvrouw M; Rega Inst for Med Res, Katholieke Univ Leuven, Belgium
Diketo compounds, such as the diketo acid (DKA) L&#8209;708,906 and S&#8209;1360, inhibit HIV replication in cell culture through inhibition of the strand transfer step of the integration process. S&#8209;1360 is in a phase I/II clinical trial. Recently, the pyranodipyrimidines have been identif
557 Analysis of Baseline Enfuvirtide (T20) Susceptibility and Co-receptor Tropism in Two-phase III Study Populations.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 557
Whitcomb JM, Huang W, Fransen S, Wrin T, Paxinos E, Toma J, Greenberg M, Sista P, Melby T, Matthews T, DeMasi R, Heilek-Snyder G, Cammack N, Hellmann N, Petropoulos C; ViroLogic, San Francisco, CA
Enfuvirtide (ENF) is the first fusion inhibitor to undergo Phase III clinical trials. Novel technologies have been developed to assess entry inhibitor susceptibility, co-receptor tropism, and HIV-1 envelope genotype. Objectives: To describe baseline (BL) ENF susceptibility, co-receptor tropism and genetic v
558 Lack of Influence of gp41 Antibodies that Cross-react with Enfuvirtide on the Efficacy and Safety of Enfuvirtide in TORO 1 and TORO 2 Phase III Trials.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 558
Walmsley S, Henry K, Katlama C, Nelson M, Lazzarin A, Reynes J, Clotet B, Salgo M, Demasi R, Delehanty J; Univ of Toronto, Canada
Enfuvirtide (ENF) is derived from HIV-1 gp41. Most infected patients (pts) have antibodies to gp41 that could cross-react with ENF. When ENF is administered to pts, potential exits for neutralization and hypersensitivity. Here we analyze the effects of gp41 antibody that cross-react with ENF on the efficacy
559 Development of a Novel Fusion Inhibitor, SC34EK: High Susceptibility to HIV Variants Resistant to Fusion Inhibitors In Vitro.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 559
Kodama E, Nameki D, Ikeuchi M, Otaka A, Tamamura H, Fujii N, Matsuoka M; Kyoto Univ, Japan
Peptide-based HIV fusion inhibitors derived from gp41 block entry of various HIV strains. To elucidate the inhibitory mechanism in detail, induction and analyses of the resistant variants were performed. Susceptibility of the synthesized peptides to the resistant variants was also investigated. METHODS: Fus
560 HIV-gp41 Peptides Based on IL-2 Structural Homologies are More Potent Inhibitors of HIV-1 Replication.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 560
Mosca JD, Lewis MG, Sattentau Q, Serres PF, McCann PP; Mymetics Corp, Annapolis, MD
We have constructed a gp41 molecule from a consensus sequence of 32 different strains of HIV-1 as a source for peptides that inhibit HIV replication across multiple HIV-1 isolates. Our modified peptides have been designed to capitalize on the 3-D molecular mimicry we have discovered between HIV-gp41 and
561 Viral Resistance and Pharmacologic Analyses of Phase I/II Study Patients Treated with the HIV-1 Entry Inhibitor PRO 542.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 561
Olson W, Israel R, Jacobson J, Vassilatos L, Tran D, Stambler N, Barish M, O'Hara B, Ketas T, Sullivan B, Moore J, Petropoulos C, Maddon P; Progenics Pharm, Inc, Tarrytown, NY
HIV-1 entry into target cells proceeds via a cascade of events involving viral attachment, coreceptor interactions, and membrane fusion. Each step of this process has been validated as a target for therapy, and HIV-1 entry inhibitors represent an emerging mode of antiretroviral therapy. PRO 542 (CD4-IgG2) i
562 TAK-220, A Novel Small Molecule Inhibitor of CCR5 has Favorable Anti-HIV Interactions with Other Antiretrovirals In Vitro.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 562
Tremblay CL, Giguel F, Hicks JL, Chou TC, Lizawa Y, Sugihara Y, Hirsch MS; CHUM, Montreal, Canada
Because of increasing viral resistance and persisting viral replication despite the use of reverse transcriptase and protease inhibitors , attachment/entry inhibitors represent a promising new class of antiretrovirals. TAK-220 is an orally bioavailable small molecule CCR5 antagonist with anti-HIV activity i
563 Anti-HIV Activity Profile of AMD070, an Orally Bioavailable CXCR4 Antagonist H.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 563
Schols D, Claes S, Hatse S, Princen K, Vermeire K, Clercq ED, Skerlj R, Bridger G, Calandra G; Rega Inst for Med Res, Katholieke Univ Leuven, Belgium
The antiviral efficacy of the CXCR4 antagonist AMD3100 was recently shown in a phase IIa clinical study, where the compound was given as a 10-day continuous infusion. This study demonstrated that CXCR4 is a viable target for antiretroviral therapy. Here, we evaluated the in vitro anti-HIV activity profile o
564 Biological and Biochemical Characterization of a Highly Polymerized CD4-Ig Fusion Protein that Mediates Efficient Antibody Dependent Cell Mediated Cytotoxicity Against HIV-infected Cells.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 564
Gupta NS, Steenbeke TD, Ryk DV, Sun P, Radaev S, Schuck P, Mavilio D, Kottilil S, Chaikin MA, Khazanie P, Rabin R, Cicala C, Arthos J, Fauci AS; Howard Hughes Med Inst (HHMI)-NIH Res Scholars Prgm, Bethesda, MD
A principal challenge in the development of an effective HIV vaccine is the elicitation of high titer neutralizing antibodies directed against the viral envelope protein gp120/41. METHODS: Effective antibody responses rely upon both F(ab)2 which confers antigen specificity and the Fc domain which mediates a
564a Potent in vivo anti-R5-HIV effects of AK602, a novel spirodiketopiperazine (SDP)-containing HIV-specific CCR5 inhibitor, in hu-PBMC-NOD-SCID mice.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 564a
Nakata H, Maeda K, Kawano Y, Miyakawa T, Shibayama S, Matsuo M, Takaoka Y, Koyanagi Y, Mitsuya H; Kumamoto University School of Medicine, Kumamoto,Japan
CCR5 represents a major chemokine receptor which R5-HIV exploits in its entry to target cells, thus serving as an attractive target for possible intervention of HIV infection. AK602, a novel agent (MW: 614) containing a unique SDP group, which potently blocks in vitro the infectivity and replication of a wi
564b Efficacy and safety of tenofovir DF (TDF) versus stavudine (d4T) when used in combination with lamivudine and efavirenz in antiretroviral naïve patients: 96-week preliminary interim results.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 564b
S Staszewski1, JE Gallant2, AL Pozniak3, JMAH Suleiman4, E DeJesus5, B Lu6, J Sayre6, A Cheng6
Through 96 weeks, combination therapy with TDF was comparable to d4T for efficacy and safety in ART-naïve patients. Patients in the TDF arm had differences in cholesterol (total, LDL and HDL) and triglycerides which were statistically significant compared to the d4T arm.
565 Response to LPVr in Experienced Patients: Effect of a Treatment Interruption.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 565
Haubrich R, Best B, Miller C, Witt M, Kemper C, Squires K, Diamond C, Heseltine P, Hellmann N, Rigby A, Capparelli E, McCutchan JA; Univ of Southern California, San Diego
Controversy exists about the impact of a treatment interruption on response to a salvage regimen. The objective of this analysis was to explore factors associated with short-term virologic response to LPVr in experienced patients (pts) who were currently on or off therapy when a LPVr regimen was begun. METH
566 Dual Therapy with Indinavir/Ritonavir 800/100 mg BID and Efavirenz 600 mg QD Effectively Treats Patients with Combination Nucleoside Analogue Failure: HIV-NAT 009 48-week Analysis.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 566
Boyd M, Duncombe C, Srasuebkul P, Hassink E, Chomchey N, Methanukroh T, Ubolyam S, Ruxrungtham K, Stek M, Lange J, Cooper D, Phanuphak P; HIV Netherlands Australia Thailand Res Collaboration
The optimal strategy for patients (pts) failing combination nucleoside analogues (NRTI) is not known. This study investigated the use of ritonavir boosted indinavir with efavirenz alone in pts failing NRTI therapy.
567 Response to a Second Treatment Regimen Following Virologic Failure.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 567
Fischl M, Ribaudo H, Collier A, Feinberg J, Rajicic N, Erice A; Univ of Miami, FL
Success of second-treatment regimens following virologic failure (VF) with a first potent treatment regimen in patients (pts) with advanced HIV infection is not well known. We examined the outcomes of second antiretroviral regimens among subjects with VF treated with zidovudine and lamivudine, plus either
568 Summary of Pooled Efficacy and Safety Analyses of Enfuvirtide Treatment for 24 Weeks in TORO 1 and TORO 2 Phase III Trials in Highly Antiretroviral Treatment-experienced Patients.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 568
Delfraissy JF, Montaner J, Eron J, DeMasi R, Chung J, Drobnes C, Delehanty J, Delfraissy JF, Montaner J, Eron J, DeMasi R, Chung J, Drobnes C, Delehanty J, Salgo M;
Primary analyses of TORO 1 and 2 established efficacy and safety and provided an assessment of treatment response among demographic, baseline (BL) characteristics, and viral sensitivity subgroups. Pooled analyses gives a more precise estimation of treatment benefit and summary of the safety of enfuvirtide (
569
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 569

Abstract not available.
570 Improved Outcomes with Earlier Initiation of HAART: Longer Follow-up of an Observational Cohort Study.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 570
Sterling T, Chaisson R, Keruly J, Moore R; Johns Hopkins Univ Sch of Med, Baltimore, MD
A number of treatment guidelines currently recommend that HAART be initiated in asymptomatic HIV-infected persons when the CD4 + lymphocyte count is = 200 cells/mm3. These recommendations are based on data from observational cohort studies, which have been limited by relatively short follow-up time. We asse
571 Possible Beneficial Effect of Sequential Use of HAART Regimens in Individuals with Undetectable Viral Load Changing Therapy Due to Drug Intolerance.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 571
Khanna N, Kaufmann G, Weber R, Furrer H, Telenti A, Vernazza P, Bernasconi E, Hirschel B, Battegay M; Univ Hosp Basel, Switzerland
Adverse events are common in individuals receiving potent antiretroviral therapy (HAART) and frequently necessitate therapy changes. The sequential use of multiple drug regimens may increase the risk of drug resistance. We studied the characteristics of individuals with frequent changes of HAART due to drug
572 Pre-treatment Factors that Predict Responses to Potent Antiretroviral Therapy: Findings from AACTG A5001.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 572
Benson CA, Collier AC, Bosch R, Bennett K, Zackin R, Team P; Univ of Colorado Hlth Sci Ctr, Denver
Defining immunologic, virologic, and host factors that influence response to Antiretroviral Therapy (ART), and their impact on long-term outcomes is key to individualizing therapy for HIV + pts. METHODS: We analyzed baseline (BL) factors associated with ART response in HIV + , ART-naïve pts in AACTG A5001 (
573 Assessing the Relative Efficacy of HAART Regimens Using Early Changes in Plasma Viremia.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 573
Hogan C, Louie M, Vasan S, Hurley A, Horowitz A, Chung C, Kim A, DiMascio M, Perelson A, Ho D, Markowitz M; Aaron Diamond AIDS Res Ctr, New York, NY
The relative efficacy of a regimen can be determined by comparing slopes of HIV-1 RNA decay in comparable patient (pt) populations. Stated mathematically antiviral efficacy (e) is proportional to the first phase slope of decay assuming d, the decay constant of virus-producing T-cells, is constant. Objective
574 Viral Dynamics and Their Relationship to Baseline Factors and Week 24 Virological Response in Non-perinatally HIV-1 Infected Adolescents Receiving HAART.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 574
Wu H, Lathey J, Spector S, Ruan P, Lindsey J, Hughes M, Douglas S, Rudy BJ, Flynn PM; Frontier Sci and Tech Res Fndn, Boston, MA
HIV dynamics have been established for HIV-1 infected adults and infants. No data have been reported on non-perinatally HIV-1 infected adolescents. In a non-randomized observational study of non-perinatally HIV-1 infected adolescents receiving highly active antiretroviral therapy (HAART), we characterized v
575 Allelic Variants of MDR1, CYP2C19, and CYP3A5: Distribution and Associations in Patients Receiving Nelfinavir or Efavirenz-containing HAART.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 575
Petersen C, Pun E, Myrand S, Lin C, Paulauskis J, Bleavins M, Johnson S, Daniels E, Haubrich R; Agouron Pharmaceuticals, Inc, a Pfizer Co, San Diego, CA
Patients (pts) receiving Highly Active Antiretroviral Therapy (HAART) have differing responses to therapy that are attributed to variable adherence and individual differences in viral and host genetic factors. Host factors have not been well-characterized. The MDR1 gene encodes P-glycoprotein, a drug efflux
576 Evidence of Low-level Viral Replication (< 50 copies/ml) Predicts Eventual Virologic Failure.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 576
Pozniak AL, Gazzard BG, Yehya M, Pillay D, Wildfire A, Cox A; Chelsea and Westminster Hosp and Imperial Coll, London, UK
A viral load between 50 and 400 copies/mL in patients (pts) previously undetectable (
577 Relationships among Four Measures of Medication Adherence and Virologic Response in ACTG 359.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 577
Fletcher CV, Testa MA, Haubrich R, Brundage R, Jiang H, Ickovics J, Martinez A, Snyder S, Gulick R; Univ of Colorado Hlth Sci Ctr, Denver
Medication adherence is a critical determinant of antiretroviral drug effectiveness, yet the optimal way to assess patient adherence is unknown. We studied 3 measures of adherence, and quantified drug concentrations in ACTG 359, a study of saquinavir soft gel (SQV) with
578 Cytokine Profiles of Antiretroviral-Naive HIV+ Patients Treated with Lopinavir/Ritonavir (Kaletra)-based Therapy for Three Years.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 578
Landay A, Tokimoto D, King M, Murphy R, Hicks C, Eron J, Gulick R, Glesby M, Wolfe P, Thompson M, White C, Benson C, Albrecht M, Kessler H, Brun S; Rush-Presbyterian-St Luke's Med Ctr, Chicago, IL
Kaletra is a co-formulation of lopinavir (LPV), an HIV protease inhibitor, and ritonovir (r), which inhibits CYP3A. On therapy, plasma cytokine levels associated with immune activity were quantitatively measured in the patient cohort treated with LPV/r for the longest
579
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 579

Abstract not available.
580 Use of Uracil N-glycosylase Negative E. Coli to Clone dUTP-containing HIV-1 DNA Generated Using a Commercial HIV-1 Genotyping System.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 580
Eshleman SH, Jones D, Petrauskene O, Jackson JB; Johns Hopkins Med Inst, Baltimore, MD
The Celera Diagnostics (formerly Applied Biosystems) ViroSeq HIV-1 Genotyping System is a commercial system for analysis of drug-resistance mutations in HIV-1. This system uses population sequencing to analyze protease and RT sequences in DNA amplified from plasma HIV-1. A dUTP/uracil N-glycosylase (UNG) co
581 Evaluation of a Rapid Phenotypic Assay for Nevirapine Resistance in Ugandan Women who Received Single-dose NVP Prophylaxis in HIVNET 012.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 581
Eshleman SH, Cheingsong R, Garcia-Lerma G, Paxinos E, Jackson JB, Heneine W; Johns Hopkins Med Inst, Baltimore, MD
The HIVNET 012 trial in Uganda demonstrated that single-dose nevirapine (NVP) can prevent HIV-1 mother-to-child transmission. NVP resistance (NVPR) can emerge in women and infants following single-dose NVP. HIV-1 genotyping can be used to detect NVPR mutations.
582 Performance of Celera Diagnostics ViroSeq HIV-1 Genotyping System on Genetically Diverse HIV-1 Strains.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 582
Marlowe N, Swanson P, Drews B, Hackett J; Celera Diagnostics, Alameda, CA
Genotyping to assess drug resistance is critical to optimal management of HIV-infected patients (pts) undergoing antiretroviral therapy. Given the increasing prevalence of non-subtype B strains in the AIDS pandemic, it is important to evaluate performance of genotyping assays on genetically divergent HIV-1
583 New Real-time RT-PCR Assay Quantifies K103N NNRTI-resistant Variant at a Frequency as Low as 0.01%.
Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 583
Palmer S, Boltz V, Maldarelli F, Halvas E,