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13th Conference on Retroviruses and Opportunistic InfectionsDenver, Colorado - February 5-8, 2006 |
Cite as: Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13:abstract no. xx
| Session 1—Workshop Program Committee Workshop for New Investigators and Trainees |
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| 1 | HIV Molecular Virology: Mechanisms of Evasion Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 1) Ned Landau Abstract not available. |
| 2 | Principles of HIV Disease Pathogenesis Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 2) John Coffin Abstract not available. |
| 3 | Advances in Eliciting HIV-Specific Immunity Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 3) Richard Koup Abstract not available. |
| 4 | NIH Funding Opportunities for Young Investigators Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 4) Opendra Sharma Abstract not available. |
| 5 | New Developments in Antiretroviral Therapy Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 5) Scott Hammer Abstract not available. |
| 6 | Pathogenesis and Management of HIV Complications Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 6) Judith Currier Abstract not available. |
| Session 2—Workshop Hands-On Computer Workshop on HIV Sequence, Immunology and Vaccine Databases |
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| 7 | Hands-On Computer Workshop on HIV Sequence, Immunology and Vaccine Databases Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 7) Ming Zhang, Bette Korber, Thomas Leitner, and Brian Gaschen Abstract not available. |
| Session 3—Symposium Dangerous Liaisons - HIV and Associated Epidemics |
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| 8 | HIV AND MALARIA-WHEN ELEPHANTS COLLIDE Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 8) Laurence Slutsker1 and B Marston2 Expanded resources are available for both malaria and HIV control, for example through the Global Fund for AIDS, Tuberculosis, and Malaria, and United States Government Initiatives. The public health response to the two diseases should include integration of programs where feasible. Available interventions include protection of blood supplies, provision of cotrimoxazole to people with HIV, and provision of insecticide-treated bed nets, particularly to HIV-infected pregnant women. |
| 9 | HIV AND TUBERCULOSIS Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 9) Anthony Harries Strategies have been devised to decrease the joint burden of HIV and TB. First, mechanisms need to be established for collaboration between HIV/AIDS and TB programmes. Second, the burden of TB in people living with HIV/AIDS should be reduced by intensified case finding, isoniazid preventive therapy, and TB infection control in health care and congregate settings. Third, the burden of HIV in TB patients should be reduced by counselling and HIV testing, care and support of HIV-related disease, cotrimoxazole preventive therapy, and HAART. The scaling-up of HAART in sub-Saharan Africa may help to decrease case fatality and recurrence rates of TB, and may lead to a decrease in the incidence of TB, provided the difficulties of combining HAART and TB treatment can be resolved. The main difficulties include additive adverse reactions, drug interactions, and management of immune reconstitution disease. The challenge ahead lies in translating TB/HIV strategies into action. |
| 10 | PREVENTION OF PNEUMOCOCCAL DISEASE IN HIV INFECTED ADULTS AND CHILDREN Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 10) Keith Klugman While mortality and multilobar disease are related to diminishing CD4 counts, mortality comparisons with HIV-uninfected patients are confounded by severity of disease and age. Response to appropriate antimicrobial therapy is generally good if such therapy is instituted early. While trimethoprim–sulphamethoxazole prophylaxis confers significant protection from mortality, the effect of this prophylaxis on pneumococcal disease is controversial as resistance emerges rapidly. The polysaccharide pneumococcal vaccine is not protective in HIV-infected adults who are not receiving ART, but studies are underway to evaluate the protective efficacy of pneumococcal conjugates in adults. Among HIV-infected children, pneumococcal conjugate vaccine protects against invasive disease due to vaccine serotypes and has been shown to reduce the burden of lower respiratory tract infections and clinical pneumonia. |
| 11 | HIV AND CANCER Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 11) Robert Newton In resource-rich settings, the widespread use of HAART has resulted in a substantial reduction in the incidence of Kaposi’s sarcoma and non-Hodgkin lymphoma among HIV-infected people but, so far, little change in the incidence of other cancers. In resource-poor settings, where HAART is still not widely available, the incidence of HIV-associated malignancies continues to increase. For example, in Africa, where the underlying viral cause of Kaposi’s sarcoma is widespread, there has been an explosion in the incidence of the tumour with the spread of HIV. In many countries in sub-Saharan Africa, it is now the most frequently reported malignancy, more common among men in some places than all other cancers combined. In contrast, in the United States, Europe, and Australia, the incidence of Kaposi’s sarcoma among HIV-infected people has declined by at least 70% since 1997, when HAART became widely available. The risk of cancer among long-term users of HAART remains uncertain. |
| Session 4—Opening Plenary and Keynote Session |
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| 12 | GREETINGS FROM THE PROGRAM COMMITTEE Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 12) Mario Stevenson Abstract not available. |
| 13 | GLOBAL HIV-1 VARIATION AND ITS IMPLICATIONS FOR VACCINE DESIGN Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 13) Bette Korber Several promising approaches from different groups will be reviewed. Building on these concepts, a new design strategy has been developed by a team at Los Alamos that utilizes machine learning methods to create sets of artificial proteins specifically designed to maximize the number of potential T-cell epitopes in proteins incorporated in a vaccine cocktail. Theoretical results suggest a small number of proteins may have the potential to give global coverage. |
| 14 | 25 YEARS OF THE HIV PANDEMIC: LESSONS LEARNED Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 14) James Curran Key biologic, behavioral, and social factors have defined the HIV/AIDS epidemic. Lessons learned from breakthroughs and barriers will be reviewed. |
| Session 5—Plenary |
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| 15 | LESSONS LEARNED FROM IN VITRO CULTIVATION OF HEPATITIS C Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 15) Takaji Wakita This infectious HCV system provides for the first time a powerful tool with which to study the viral life cycle, to construct anti-viral strategies and to develop effective vaccines. |
| Session 6—Plenary |
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| 16 | TEN YEARS OF HAART: PRINCIPLES FOR THE FUTURE Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 16) John G Bartlett The future will bring new drugs from one of medicine's richest pipelines, simplified regimens, opt-out testing, a healthcare infrastructure in developing counties, and the potential for 30,000,000 life-years saved. |
| Session 7—Oral Abstracts Treatment and Clinical Complications in Pediatric and Adolescent HIV |
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| 17 | PHASE I/II STUDY OF A ONCE-DAILY REGIMEN OF EMTRICITABINE, DIDANOSINE, AND EFAVIRENZ IN HIV-INFECTED, THERAPY-NAÏVE CHILDREN AND ADOLESCENTS: PACTG PROTOCOL 1021 Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 17) Ross McKinney1, M Rathore2, C Hu3, P Britto3, M Smith4, L Serchuck4, J Rodman5, L Draper6, L Reynolds7, G Chittick8, and Pediatric ACTG Protocol 1021 Team A once-daily regimen of FTC, ddI, and EFV proved to be safe and effective in this 37 subject, 2-year phase I/II study. By intent-to-treat analysis, 72% of subjects demonstrated sustained HIV viral load suppression to <50 copies/mL through week 96. |
| 18 | 3-NRTI HAART SIMPLIFICATION IN CHILDREN IS EFFECTIVE IN MAINTAINING VIROLOGICAL AND IMMUNOLOGICAL CONTROL AFTER 108 WEEKS Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 18) Guido Castelli-Gattinara1, M Amicosante2, P Palma1, C Cancrini2, M Romiti2, S Bernardi1, A Martino1, E Caropreso1, and P Rossi1,2 HAART simplification after an induction therapy allows to maintain a complete and long-term immunological and virological control with significant improvement of dyslipidemia. The progressive increase of specific cytotoxic T lymphocyte response observed in some patients can be related to an enhanced viral replication in lymph nodes or an increased frequency of blips. |
| 19 | REPEATED SUPERVISED TREATMENT INTERRUPTION WITH PROGRESSIVE INCREASES IN "OFF-TREATMENT" DURATION RESULTS IN ENHANCED VIROLOGIC CONTROL IN A SUBSET OF PEDIATRIC INDIVIDUALS Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 19) William Borkowsky1, E McFarland2, R Yogev3, P Muresan4, L Frenkel5, T Fenton4, J Moye6, E Capparelli7, P Harding2, N Ellis8, and the Pediatric AIDS Clinical Trials Group 1015 Team A subset of pediatric patients undergoing progressively lengthening STI demonstrated improved virologic control despite longer periods off therapy. This effect is seen in those who have had ≥13 interruptions, resulting in STI that eventually exceed 27 days in length. Enhanced HIV-specific immune responses may have played a role in this phenomenon. Selection of less replication competent virus may have played a role in one of the individuals. |
| 20 | DENDRITIC CELL FUNCTION IN SURVIVING CHILDREN AND ADOLESCENTS WITH LONG-TERM HIV INFECTION ACQUIRED PERINATALLY Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 20) Seema Desai, A Chaparro, H Liu, G Scott, P Haslett, R Pahwa, and S Pahwa The most striking finding was a reduced expression of CCR7 in TLR-stimulated pDC of HIV-infected children who have poor immunologic response or ongoing, active viral replication while on ART. A defect in homing of the pDC to lymph nodes could break the link between innate and adaptive immune response to HIV. |
| 21 | PREVALENCE OF PRIMARY HIV DRUG RESISTANCE AMONG RECENTLY INFECTED ADOLESCENTS; A MULTICENTER ADOLESCENT TRIALS NETWORK STUDY: ATN029 Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 21) Rolando Viani1, L Peralta2, G Aldrovandi3, B Kapogiannis4, R Mitchell5, S Spector1, Y Lie6, J Weidler6, M Bates6, and C Wilson7 The prevalence of primary HIV resistance, particularly to NNRTI (18%), in these recently infected youth is among the highest reported in the United States. These data support the extension of current guidelines for resistance testing in HIV-infected adults, to adolescents prior to initiating HAART. |
| 22 | INCIDENCE OF TUBERCULOSIS IN HIV-INFECTED CHILDREN: THE INFLUENCE OF HAART Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 22) Neil Martinson1,2, H Moultrieh1, G Barry1, A Violari1, M Cotton3, R Van Niekerk1, L Kalete1, A Coovadia1, T Meyers1, and G Gray1 Incidence of TB in HIV-infected children is high but few cases are confirmed. Overall, HAART protects HIV-infected children from TB but to a lesser extent than in adults. In this preliminary analysis, HAART was not protective for bacteriologically or biopsy confirmed TB. Prospective studies should confirm our findings. |
| 23 | INSULIN RESISTANCE, LIPODYSTROPHY AND ASSOCIATED METABOLIC CHANGES IN HIV-INFECTED CHILDREN Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 23) Raffaella Rosso1, A Parodi2, A Di Biagio1, L Di Stefano1, C Torrisi2, C Dentone1, G D'Annunzio2, C Viscoli3, and M Vignolo2 IR in HIV-infected children seems common and significantly different than in the control population. Fasting surrogate markers suggest increased IR as in the HIV-infected adults, which could be related to not only the cumulative ART exposure but the HIV infection itself. The association between type and duration of HAART and IR was not considered, due to the small group and the widely different type of therapy received by patients. |
| 24 | THE PRICE OF ANTIRETROVIRAL THERAPY IN CHILDREN: FOCUS ON METABOLIC MORBIDITIES Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 24) Grace McComsey This overview summarizes the epidemiology, clinical presentation, and management of lipodystrophy, dyslipidemia, insulin resistance, hyperlactatemia, and decreased bone mineral density in HIV-infected children. In addition to describing the available pediatric data, this presentation will summarize and put in perspective for pediatricians the reported data on these complications from studies of HIV-infected adults. |
| Session 8—Oral Abstracts New Insights into Transmission and Disease Progression |
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| 25 | ROUTINE HIV TESTING IN BOTSWANA: A POPULATION-BASED STUDY ON ATTITUDES, PRACTICES, AND HUMAN RIGHTS CONCERNS Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 25) Sheri Weiser1, M Heisler2, K Leiter3, F Percy-De Korte3, S Tlou4, S Demonner2, N Phaladze4, D Bangsberg5, and V Iacopino3 Routine testing is widely supported and may reduce barriers to testing in Botswana. As routine testing is adopted elsewhere, measures should be implemented to assure true informed consent, and human rights safeguards including protection from HIV-related discrimination, and protection of women against partner violence related to testing. |
| 26 | HLA-B Bw4 AND Bw6 ALLELES AND RISK FOR HIV-1 TRANSMISSION IN HIV-SERODISCORDANT HETEROSEXUAL COUPLES Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 26) Tania Welzel1, X Gao2, R Pfeiffer1, M Martin2, J Goedert1, M Carrington2, and T O'Brien1 The presence of HLA-Bw4 alleles in HIV-1- infected men was associated with a decreased risk of HIV transmission from HIV-positive men to their female sex partners. It might be possible that HLA-B Bw4 allele carriers have a decreased seminal HIV RNA load which leads to a decreased HIV-1 transmission risk. |
| 27 | TRENDS IN HIV DIAGNOSIS AMONG NON-HISPANIC BLACK AMERICANS, 2001-2004 Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 27) Tonji Durant, A Satcher, J Prejean, X Wei, and L Lee NHBs accounted for most HIV diagnoses from 2001 to 2004. Among NHBs, trends in transmission remained stable or declined in all categories analyzed except MSMs. However, a large disparity in HIV diagnoses remains between NHBs and other race/ethnic groups. These results underscore the impact of the HIV/AIDS epidemic on NHBs and the need to continue monitoring trends particularly among MSM, the largest transmission category. Accelerating the decline in HIV diagnoses among NHBs and narrowing the race/ethnic disparity remains a significant public health objective. |
| 28 | HIGH HIV PREVALENCE AND INCIDENCE OBSERVED AMONG AFRICAN-AMERICAN MEN WHO HAVE SEX WITH MEN (MSM) IN BALTIMORE: THE BEHAVIORAL SURVEILLANCE RESEARCH (BESURE) STUDY Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 28) Frangiscos Sifakis1, C Flynn2, R Montes De Oca1, M Hilton1, N Tomoyasu2, and D Celentano1 HIV prevalence (32.3%) and incidence (9.2% per year) are high among MSM in Baltimore and of particular concern among African American MSM (45.6% and 15.4% per year, respectively). Unrecognized infection among African American MSM remains high (63.4%). HIV prevention and education in Baltimore must promote HIV testing and better address the needs of African American MSM. |
| 29 | NON-AIDS RELATED MORTALITY RISK EXCEEDS AIDS-RELATED MORTALITY AMONG INJECTING DRUG USERS WITH CD4+ COUNTS ABOVE 200 CELLS/MM3 Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 29) Bryan Lau1,2, S Gange2, and R Moore1,2 Competing risk analyses indicate that non-AIDS related mortality exceeds AIDS-related mortality for those enrolling with higher CD4 counts, especially among IDU. Efforts to reduce mortality among HIV-infected populations will be hampered unless attention is also directed towards conditions that may not traditionally be considered HIV-related. |
| 30 | PRIMARY CAUSES OF MORTALITY IN HIV DISCORDANT ZAMBIAN COUPLES Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 30) Philip J Peters1,2, I Zulu1,3, N Kancheya1,3, S Lakhi1,3, E Chomba1,3, D J Kim1,4, I Brill1,4, J Meinzen-Derr1,4, A Fraser-Bell1,5, and S Allen1,5,6 HIV positive Zambians had comparable survival times to pre-ART cohorts in high-income countries. MKC staging is a powerful, low-cost tool to identify people at high risk for death who need urgent evaluation for ART. The burden of mortality due to tuberculosis and chronic gastroenteritis highlights the need for parallel investment in tuberculosis and diarrheal disease treatment as ART scales up. |
| 31LB | NATIONAL HIV PREVALENCE AND BED HIV INCIDENCE ESTIMATES: SOUTH AFRICA 2005 Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 31LB) Thomas Rehle1, A Puren2, K Zuma1, V Pillay1, P Dana1, and O Shisana1 The addition of HIV incidence testing to the survey protocol enables a more precise and timely analysis of the current HIV-transmission dynamics and a more relevant assessment of the effect of prevention programs in South Africa. |
| 32LB | PREVENTION OF RECTAL SHIV TRANSMISSION IN MACAQUES BY TENOFOVIR/FTC COMBINATION Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 32LB) J Garcia-Lerma, R Otten, S Qari, E Jackson, W Luo, M Monsour, R Schinazi, R Janssen, T Folks, and Walid Heneine TDF/FTC combination provides a high level of protection against repeated virus challenges, demonstrating that chemoprophylaxis with potent antiretrovirals is an effective strategy for preventing sexual HIV transmission. |
| 33LB | EFFECT OF HSV-2 SUPPRESSIVE THERAPY ON HIV-1 GENITAL SHEDDING AND PLASMA VIRAL LOAD: A PROOF OF CONCEPT RANDOMIZED DOUBLE-BLIND PLACEBO CONTROLLED TRIAL (ANRS 1285 TRIAL) Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 33LB) Nicolas Nagot1,2, A Ouedraogo2, P Mayaud1, I Konate2, L Vergne2, H Weiss1, V Foulongne3, D Djagbare2, M Segongy3, P Vande Perre3, and ANRS 1285 Study Group Active HSV-2 infection is causally related to increased HIV-1 genital shedding, with implications at the systemic level. HSV-2 control interventions may contribute to reduce sexual transmissibility of HIV-1 and may delay HAART eligibility in dually infected women. |
| 34LBa | ASSOCIATION BETWEEN GENITAL SCHISTOSOMIASIS AND HIV IN RURAL ZIMBABWEAN WOMEN Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 34LBa) Eyrun F Kjetland1, P Ndhlovu2,3, T Mduluza2,3, E Gomo2,3, N Midzi3, L Gwanzura2, P Mason2,4, L Sandvik5, H Friis6, and S Gundersen7 In S. haematobium-endemic areas, HIV may have spread with genital schistosomiasis, rather than STD, as an essential risk factor for heterosexual transmission. This study indicates that schistosomiasis control may perhaps be an important auxiliary in HIV prevention. The possibility of reduced HIV transmission in schistosomiasis-endemic areas adds new intervention points in the battle against HIV. Prospective studies are needed to confirm the association. |
| 34LBb | INVESTIGATION OF REPORTS OF EXCESSIVE FALSE-POSITIVE ORAL FLUID RAPID HIV TESTS Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 34LBb) Bernard Branson1, L Wesolowski1, K Delaney1, M Mavinkurve2, T Dowling3, and D Mackellar1 Specificity of the OraQuick test is slightly lower with oral fluid than with whole blood, but still well above the FDA’s minimum threshold of 98% for rapid HIV tests. Investigation continues to identify site-specific factors that may lead to more FP oral fluid test results than expected. |
| Session 9—Oral Abstracts Studies of Pathogenic and Non-Pathogenic Infection |
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| 35 | ENDEMIC INFECTION OF CENTRAL CHIMPANZEES (PAN TROGLODYTES TROGLODYTES) BY SIMIAN IMMUNODEFICIENCY VIRUS Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 35) Brandon Keele1, F Heuverswyn2, Y Li1, E Bailes3, S Loul4, J Brookfield3, G Shaw1, P Sharp3, M Peeters2, and B Hahn1 SIVcpz is widely, but unevenly distributed among wild P. t. troglodytes (but not P. t. vellerosus) apes in southern Cameroon, indicating an existing chimpanzee reservoir. Circulating SIVcpz strains exhibit extensive genetic diversity, but form geographically defined lineages, likely reflecting P. t. troglodytes populations with non-overlapping habitats. Two of these endemically infected populations gave rise HIV-1 groups M and N, and may still serve as a source of human infection. The geographic origin of group O remains to be identified. |
| 36 | SEVERE MUCOSAL DEPLETION OF CD4+ T CELLS IN ABSENCE OF GENERALIZED IMMUNE ACTIVATION DURING NON-PATHOGENIC SIV-INFECTED SOOTY MANGABEYS Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 36) Shari Gordon1, J Engram1, J Milush2, R Dunham1, N Klatt1, E Strobert3, I Pandrea4, S Staprans1, D Sodora2, and G Silvestri1 Natural, non-pathogenic SIV infection of sooty mangabeys is characterized by a significant depletion of CD4+ T cells in the MALT in the context of normal peripheral blood CD4+ T cell counts and the absence of generalized immune activation. These results suggest that the clinical onset of AIDS may require both the depletion of MALT-associated CD4+ T cells and the presence of significant mucosal or systemic immune activation. |
| 37 | DRAMATIC CD4+ T CELL DEPLETION IN THE INTESTINE IS A HALLMARK OF SIV INFECTION IN NATURAL HOSTS Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 37) Ivona Pandrea1, C Apetrei1, J Dufour1, N Dillon1, J Barbercheck1, N Katz1, P Marx1, V Hirsch2, A Lackner1, and R Veazey1 Our study demonstrates that, as in rhesus macaques, in natural hosts of SIV, CD4+ T cell depletion occurs preferentially in the gastrointestinal tract. We therefore show for the first time that a massive CD4+ T cell depletion during primary infection at the main site of lentiviral infection does not necessarily result in progressive infection and that in natural hosts of SIV, this depletion has no significant pathogenic consequences. In hosts controlling chronic SIV infection, such as rhesus macaques infected with SIVagm, the immune restoration in the intestine is only partial. These data call for further investigation of the mechanisms controlling the deleterious effects of SIV in both hosts. |
| 38 | HIGH FREQUENCIES OF INFECTED CD4+ T CELLS IN THE GASTROINTESTINAL TRACT IS ASSOCIATED WITH POOR MUCOSAL IMMUNE RECONSTITUTION AFTER HAART Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 38) Jason Brenchley1, T Schacker2, D Price1, M Larson2, A Khoruts2, G Beilman2, A Haase2, and D Douek1 These data strongly suggest that HAART does not adequately suppress viral replication at mucosal surfaces and this residual viral replication maintains the depletion of mucosal CD4+ T cells. Moreover, this continued depletion may be related to high levels of infection within blood CD4+ T cells with a mucosal homing phenotype. Taken together, these data explore the dynamics of reconstitution between different anatomical sites and suggest that ongoing viral replication at particular sites may impair immune reconstitution. |
| 39 | INITIATION OF HAART DURING PRIMARY HIV-1 INFECTION RESULTS IN BETTER RESTORATION AND MAINTENANCE OF MUCOSAL CD4+ T CELLS Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 39) M Guadalupe1, E Reay1, S Sankaran1, M George1, B Shacklett1, J Flamm2, J Wegelin1, T Prindiville1, Satya Dandekar1, and S Dandekar1 Our findings indicate that initiation of HAART during primary HIV-1 infection was more effective in restoring or maintaining mucosal CD4+ T cells and suppressing viral loads than initiation during chronic HIV-1 infection. Furthermore, these data emphasize the importance of monitoring clinical disease progression in lymphoid tissues as well as peripheral blood for a more accurate assessment of the efficacy of HAART. |
| 40 | RESTORATION OF MEMORY CD4+ CCR5+ T CELLS IN THE GASTROINTESTINAL TRACT DURING THE CHRONIC STAGE OF SIV INFECTION PREDICTS LONG-TERM NON-PROGRESSION Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 40) Binhua Ling, R Veazey, M Hart, M Kuroda, B Pahar, and P Marx Profound depletion of memory CD4+CCR5+ cells in GALT was indistinguishable between disease progressors and LTNP at the acute stage of infection. Restoration of mucosal memory CD4+CCR5+ cells during the chronic phase predicted LTNP. Sufficient CD8+ T cells may be essential for controlling SIV infection in GALT and required for restoration of memory CD4+CCR5+ T cells. |
| 41 | CD4+ T-CELL QUANTIFICATION WITHIN GUT LAMINA PROPRIA OF HIV PATIENTS AFTER HAART Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 41) Jason Baker, M Larson, A Khoruts, A Haase, and T Schacker The effector memory CD4+ T cells in GALT are rapidly depleted, and our data suggest a limited capacity for repletion with HAART. Further work is required to understand the reasons why repletion of the gut is limited compared to the peripheral expansion of the total CD4+ T-cell population, and if a longer duration of HAART would result in better recovery of CD4+ T cells in secondary lymphatic tissues. |
| 42 | AIDS-DEFINING CD4 T-CELL LEVELS CORRELATE WITH EXPANDED CO-RECEPTOR USAGE DURING NONPATHOGENIC SIVsm INFECTION OF SOOTY MANGABEYS Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 42) Jeffrey Milush1, J Reeves2, D Zhou1, A Muthukumar1, E Chacko1, S Gordon3, K Stefano-Cole4, S Staprans3, G Silvestri3, and D Sodora1 These data indicate that expanded co-receptor usage can occur in SIV-infected sooty mangabeys. Moreover, CD4 levels <100/mL blood are likely sustained by direct viral killing of T-cell targets; bystander-associated cell death does not appear to play a major role. The CD4low sooty mangabeys provide evidence that AIDS-defining CD4 levels and progression to clinical AIDS can be separated; increased immune activation that occurs in HIV+ humans, but not in sooty mangabeys, appears to be crucial for progression to AIDS. |
| 43 | CXCR4-TROPIC VIRUSES ARE COMMON AMONG ANTIRETROVIRAL TREATED PATIENTS WITH DETECTABLE VIREMIA AND ASSOCIATED WITH LOWER TREATMENT-MEDIATED CD4 GAINS Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 43) Peter Hunt1, J Martin1, M Bates2, W Huang2, S Spudich1, R Price1, D Williamson3, E Sinclair3, R Hoh1, and S Deeks1 Treated patients with partial viral suppression are more likely than untreated patients to harbor dual/mixed or X4-tropic viruses, independent of the extent of current or prior immunodeficiency. Dual/mixed or X4 tropism is also associated with fewer treatment-mediated CD4+ T cell gains, perhaps due to a greater ability to deplete resting memory and naïve CD4 cells. |
| 44LB | THE EFFECT OF HIV SUBTYPE ON RAPID DISEASE PROGRESSION IN RAKAI, UGANDA Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 44) Oliver Laeyendecker1, X Li2, M Arroyo3, F McCutchan3, R Gray2, M Wawer4, D Serwadda5, F Nalugoda6, G Kigozi6, T Quinn1, and Rakai Health Science Program Viral load had a significant effect on disease progression over longer follow-up time, but did not predict death within 24 months of infection. Subtype D and recombinant strains incorporating subtype D are pathogenic than subtype A, probably due to the increased frequency X4 co-receptor tropism in subtype D. These findings suggest that knowledge of HIV subtype might be useful in clinical management of HIV infection in Uganda. |
| Session 10—Oral Abstracts and Research Overview Antiretroviral Therapy I: New Agents and New Insights |
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| 45 | GS9148: A NOVEL NUCLEOTIDE ACTIVE AGAINST HIV-1 VARIANTS WITH DRUG-RESISTANCE MUTATIONS IN REVERSE TRANSCRIPTASE Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 45) Tomas Cihlar1, A Ray1, D Boojamra1, L Zhang1, H Hui1, D Grant1, K White1, M Desai1, N Parkin2, and R Mackman1 GS9148 exhibits a favorable in vitro pharmacological profile including lower levels of resistance than approved NRTIs, an indication of potential efficacy against existing NRTI-resistant viruses. The amidate prodrug of GS9148 is an attractive candidate for further development with potential for once daily dosing and activity in both treatment-naïve and NRTI-experienced patients. |
| 46 | 1-(β-D-DIOXOLANE) THYMINE IS EFFECTIVE AGAINST HIV-1-CONTAINING TAM AND M184V Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 46) Johan Lennerstrand1, G Bluemling1, M Ruckstuhl1, M Bennett1, C Chu2, and R Schinazi1 Compared with other RT inhibitors, DOT-TP was overall more effective against RT-containing TAM, M184V, and K65R. The 69-mutant demonstrated a lower level of resistance to DOT-TP than AZT-TP and TFV-DP. However, as expected for dioxolane nucleosides, an increased non-ATP-dependent resistance was found with the 151-mutant. These enzymatic studies indicate that DOT resistance mainly involves binding discrimination and only modest ATP-dependent excision. |
| 47 | NUCLEOTIDE-COMPETING REVERSE TRANSCRIPTASE INHIBITORS FORM A STABLE DEAD-END COMPLEX WITH THE HIV-1 ENZYME Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 47) M Ehteshami1, J Deval1, S Barry1, D Jochmans2, K Hertogs2, and Matthias Götte1 The results provide strong evidence to suggest that NcRTI-1 can partially occupy the nucleotide binding site of HIV-1 RT. The compound forms a dead-end complex that prevents the incorporation of dNTP substrates. Our biochemical data are consistent with cell-based inhibition measurements showing that the M184V change is associated with decreased susceptibility to NcRTI-1, while K65R confers hypersusceptibility. |
| 48 | NEXT GENERATION HIV PEPTIDE FUSION INHIBITOR CANDIDATES ACHIEVE POTENT, DURABLE SUPPRESSION OF VIRUS REPLICATION IN VITRO AND IMPROVED PHARMACOKINETIC PROPERTIES Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 48) Mary Delmedico1, B Bray1, N Cammack2, D Davison1, J Dwyer1, L Frick1, N Tvermoes1, S Wring1, H Zhang1, and M Greenberg1 TR-290999 and TR-291144 demonstrate: potent in vitro antiviral activity; durable in vitro control of virus replication; and slow, extended clearance properties in monkeys. The combination of potency, durability, and pharmacokinetic and appropriate physical properties enables the evaluation of sustained-release formulations to provide once/week dosing. Further study of these novel, next-generation fusion inhibitors is in progress. |
| 49LB | DEVELOPMENT OF NOVEL ORALLY BIOAVAILABLE CXCR4 ANTAGONISTS, KRH-3955 AND KRH-3140: BINDING SPECIFICITY, PHARMACOKINETICS AND ANTI-HIV-1 ACTIVITY IN VIVO AND IN VITRO Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 49LB) Yuetsu Tanaka1, K Okuma1, R Tanaka1, S Kumakura2, A Shimoyamada2, K Hirose2, M Yanaka2, T Murakami3, and N Yamamoto3 KRH3955 and KRH-3140 are orally bioavailable CXCR4 antagonists with potent anti-X4 HIV-1 activities in vivo, indicating that these drugs may be desirable additives to an anti-HIV-1 therapy. |
| 50LB | EXECUTION OF A HIGH THROUGHPUT HIV-1 REPLICATION SCREEN AND THE IDENTIFICATION OF A NOVEL SMALL MOLECULE INHIBITOR THAT TARGETS HIV-1 ENVELOPE MATURATION Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 50LB) Wade Blair, J Cao, L Jackson, Q Peng, J Isaacson, S Butler, H Wu, A Chu, and A Patick UK-201844 represents the prototype for a unique HIV-1 inhibitor class that directly or indirectly inhibits HIV-1 gp160 processing, resulting in the production of virions with non-functional Env proteins. |
| 51 | TOWARD GENE KNOCK-OUT THERAPY FOR AIDS/HIV: TARGETED DISRUPTION OF CCR5 USING ENGINEERED ZINC FINGER PROTEIN NUCLEASES Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 51) Yann Jouvenot1, E Perez2, F Urnov1, J Miller1, E Rebar1, M Holmes1, D Ando1, J Riley2, P Gregory1, and C June2 The frequency of gene disruption observed supports its examination as a possible method for the therapeutic modification of isolated patient cells to generate HIV-resistant T cells or hematopoietic precursors. |
| 52 | PHARMACOKINETICS/PHARMACODYNAMICS OF PA-457 IN A 10-DAY MULTIPLE DOSE MONOTHERAPY TRIAL IN HIV-INFECTED PATIENTS Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 52) Patrick Smith1, A Forrest1, G Beatty2, J Jacobson3, J Lalezari4, J Eron5, R Pollard6, M Saag7, J Doto8, and D Martin8 PA-457 demonstrated significant antiviral activity at the higher dose levels, with greater activity observed with increasing drug exposure. Additional antiviral activity is likely with doses higher than those used in this trial, as Emax was not reached at 200 mg. Similar to other available ART, pharmacokinetics/pharmacodynamics appears to be an important determinant of PA-457 activity. Additional studies to evaluate the potential role of PA-457 in the treatment of HIV-infection are warranted. |
| 53 | THE ROLE OF DRUG INTERACTION STUDIES IN EARLY ANTIRETROVIRAL DRUG DEVELOPMENT Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 53) Kimberly Struble Drug interaction information is important for the safe use of combination ART. Early identification of potential interactions and appropriate clinical management of these interactions can lead to more effective long-term therapy by reducing drug toxicity or by delaying the development of resistance in antiretroviral naïve and experienced patients. |
| Session 14—Symposium HIV Prevention Research: New Advances, Continued Challenges |
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| 54 | ANTIRETROVIRAL THERAPY TO PREVENT SEXUAL TRANSMISSION OF HIV Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 54) Myron Cohen These concerns notwithstanding, the public health opportunities for ART as prevention are substantial, and ongoing research is likely to improve this important application. |
| 55 | BEYOND CONDOMS: CHEMICAL AND PHYSICAL BARRIERS TO PROTECT WOMEN FROM HIV Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 55) Sharon Hillier There is a growing consensus that a highly effective female-controlled method will require a combination of products or methods, and combining cervical barriers and microbicides offers a compelling approach to HIV/ sexually transmitted infections prevention. Additional work is focused on development of microbicides, which are not coitally dependent. |
| 56 | VACCINES TO INDUCE CTL RESPONSES TO HIV IN IMMUNOCOMPETENT INDIVIDUALS: STATE OF THE FIELD Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 56) Lawrence Corey The 2 leading candidates are a recombinant Ad5 vector containing gag-pol-nef made by Merck Corporation, and a multivalent DNA followed by Ad5 vaccine made by the NIH Vaccine Research Center. These vaccines are entering advanced clinical trials and a review of their immunogenicity and approaches to evaluate their potential efficacy in humans will be discussed. |
| 57 | HIV VOLUNTARY TESTING AND COUNSELING (VCT) DIVIDES, BUT IT SHOULD UNITE Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 57) Thomas Coates The presentation will conclude with ongoing and needed research in HIV VCT, with an emphasis on the tension between the preventive and diagnostic aims of HIV VCT, and the kinds of research needed to resolve and eliminate such tension. |
| Session 15—Symposium Cellular Co-Factors and Innate Resistance |
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| 58 | HIV INFECTION OF NON-DIVIDING CELLS Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 58) Michael Emerman, and M Yamashita Thus, we showed that Gag is the major determinant for the ability of retroviruses to infect non-dividing cells, and suggest that uncoating, rather than nuclear import is the rate-limiting step. |
| 59 | RESTRICTION OF RETROVIRUS REPLICATION Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 59) Jonathan Stoye, M Yap, M Dodding, and S Okhura The critical interaction between CA and Trim-CypA appears to take place soon after viral entry. Quantitative PCR analysis on viral reverse transcriptase products revealed that the different fusion proteins block HIV-1 at two distinct stages of its lifecycle. Both blocks are distinguishable from that associated with Fv1. With Trim1 and Trim18, timing of replication arrest is dependent on the length of the Trim component of the fusion protein. These observations suggest that restriction factor binding can have different mechanistic consequences. |
| 60 | EVOLUTION OF INTRINSIC IMMUNITY AGAINST RETROVIRUSES IN PRIMATE GENOMES Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 60) Harmit Malik, S Sawyer, M OhAinle, J Kerns, L Wu, and M Emerman We have been able to use the signature of rapid evolution to identify a small “patch” in the TRIM5α protein that is responsible for antiviral specificity, highlighting the power of such evolutionary analyses. Screening human populations for genetic variation in TRIM5α, we uncovered an impaired allele at an unexpectedly high frequency (~50%) in certain ethnic groups. We can use the evolutionary insights gained from APOBEC3G and TRIM5α, as well as human population genetics, to identify other, novel restriction factors employed for retroviral defense by primate genomes. |
| 61 | NEW INSIGHTS INTO THE ANTIVIRAL ACTION OF APOBEC3G Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 61) Warner Greene, Y L Chiu, J Kreisberg, V Soros, M Santiago, K Stopak, and W Yonemoto These results indicate that the post-entry restricting activity afforded by LMM A3G is temporarily inactivated resting CD4 T cells present in lymphatic tissues. Our studies indicate that the local production of select cytokines including interleukin (IL)-2 and IL-15 in these lymphatic tissues plays a key role in the induced assembly of HMM A3G complexes. Addition of higher concentrations of IL-2, IL-15, or IL-7 as single stimuli also activates A3G gene expression leading to the induction of A3G mRNA and protein expression. |
| Session 16—Oral Abstracts Implementing Antiretroviral Therapy in Developing Countries |
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| 62 | ADHERENCE TO NNRTI-BASED REGIMENS AND VIROLOGIC OUTCOMES IN HIV-INFECTED SOUTH AFRICAN ADULTS Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 62) Jean Nachega1, M Hislop2, L Rengensberg2, R Chaisson3, and G Maartens4 High levels of adherence, as assessed by pharmacy claim data in a private-sector management program, strongly predict viral suppression in HIV-positive South African adults on NNRTI-based ART. Pharmacy records are a simple and a valid program-level adherence monitoring tool. |
| 63 | MORTALITY AND CAUSES OF DEATH IN ADULTS RECEIVING HAART IN SENEGAL: A 7-YEAR COHORT STUDY Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 63) J F Etard1,2, A Dieng2, A Diouf2, M Thierry-Mieg2, V Cilote2,3, B Taverne1,2, S Mboup4, I Ndoye5, Eric Delaporte1, P Sow4, and ANRS 1290 This study underlines the early mortality pattern after HAART initiation, reports long-term trend in mortality and its predictors among patients under HARRT in an African setting, and highlights the leading role of mycobacterial infections in the causes of death. |
| 64 | RAPID SCALE-UP OF ANTIRETROVIRAL SERVICES IN ZAMBIA: 1-YEAR CLINICAL AND IMMUNOLOGIC OUTCOMES Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 64) Moses Sinkala1, J Levy2, I Zulu3, A Mwango1, E Stringer2, B Chi2, S Reid2, T Ellerbrock4, M Bulterys5, and J Stringer2 Rapid initiation of ART in a programmatic setting led to favorable clinical outcomes at 6 and 12 months in Zambia. Advanced HIV disease was a very strong predictor of mortality in this population, suggesting that every effort should be made to identify and treat infected patients earlier in their disease course. |
| 65 | PERFORMANCE CHARACTERISTICS OF NON-CD4-BASED CRITERIA FOR INITIATION OF ART IN AN AMBULATORY CLINIC POPULATION IN PHNOM PENH, CAMBODIA Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 65) Chel Sarim1, J Elliott1, S Huffam1, H Chenda1, P Sophea1, S Vonthanak1, J Kaldor2, D Cooper2, and M Vun1 Basing initiation of ART on clinical criteria alone would have resulted in poor treatment decision-making in this population. Addition of lymphocyte count improved performance, but treatment misallocation remained substantial. These data strongly support the role of CD4 testing in criteria for initiation of ART in an ambulatory setting. |
| 66 | REGIMEN DURABILITY AND TOLERABILITY TO 36-MONTH DURATION ON ART IN KHAYELITSHA, SOUTH AFRICA Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 66) Andrew Boulle1, G Van Cutsem2, D Coetzee1, K Hilderbrand1,2, E Goemaere2, and G Maartens3 The substitution of AZT with d4T in the first-line regimen has resulted in fewer regimen changes due to anemia or neutropenia, and correspondingly a higher proportion of changes due to peripheral neuropathy and lactic acidosis. The incidence of symptomatic hyperlactatemia or lactic acidosis is higher in this cohort than that anticipated from the literature. There is generally a clinical delay in switching to second-line compared with the point that virological failure is confirmed on laboratory criteria. The Khayelitsha cohort provides an opportunity to reliably explore regimen durability and tolerability to 36 months in the context of treatment in a developing country. |
| 67 | WHEN ARE ADULTS IN RESOURCE-CONSTRAINED SETTINGS MOST LIKELY TO EXPERIENCE AN HIV-ASSOCIATED ILLNESS FOLLOWING HAART INITIATION AND WHAT IS IT RELATED TO? Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 67) Paula Braitstein1, M Brinkhof1, M Schechter2,3, N Kumarasamy4, D Nash5, A Boulle6, E Ekong7, F Dabis8, E Balestre8, M Egger1, and the Antiretroviral Treatment in Lower Income Countries (ART-LINC) Collaboration Although the completeness of ascertainment of HIV-associated illness events in ART-LINC is unclear at the moment, and diagnostic criteria differ across centers, these results indicate a considerably higher risk of new HIV-associated illness and TB events during months 1 to 2 than later months post-HAART. The increased risk early on may be associated with the immune reconstitution syndrome. Age, sex, baseline CD4 count, initial treatment regimen, and having a history of HIV-associated illness or TB at baseline were important predictive factors. |
| 68 | TUBERCULOSIS AMONG HIV-INFECTED PATIENTS RECEIVING HAART: LONG-TERM INCIDENCE AND RISK FACTORS IN A SOUTH AFRICAN COHORT Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no.68) Stephen Lawn1,2, M Badri1, and R Wood1 TB incidence continued to decrease during the first 5 years of HAART, with a 3.5-fold reduction occurring beyond the first year of treatment. HAART may therefore contribute more to TB control in low-income countries than has previously been estimated. Patients with advanced pre-treatment immunodeficiency had persistently increased risk of TB during HAART and TB occurred among those with poor immunological recovery during HAART. Advanced immunodeficiency among patients accessing HAART in low-income countries may limit immune recovery and lead to chronically heightened risk of TB. |
| 69 | PREVALENCE OF HIV AND UNDIAGNOSED TUBERCULOSIS IN A PERI-URBAN COMMUNITY IN SOUTH AFRICA Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 69) Linda-Gail Bekker1, K Middelkoop1, L Myer2, A Whitelaw2, A Grant3, G Kaplan4, S Lawn1,3, and R Wood1 This community has a very high prevalence of both TB and HIV and there are more individuals in the community with undiagnosed TB than individuals already on treatment. The majority of individuals with previously undiagnosed TB are HIV-uninfected, while the known cases are predominantly HIV-infected. |
| Session 18—Plenary |
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| 70 | WHERE AIDS CAME FROM Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 70) Paul Sharp The closest SIVcpz relatives of HIV-1 infect one particular subspecies of chimpanzees, Pan troglodytes troglodytes, in West Central Africa. We have now found widespread endemic infection in these apes, with SIVcpz prevalence rates over 20% in some communities. SIVcpz strains exhibit a local phylogeographic clustering, allowing us to trace the origins of pandemic (group M) and nonpandemic (group N) HIV-1 to distinct, geographically isolated chimpanzee communities in southern Cameroon. Thus, 25 years into the AIDS epidemic, the origins of this newly emerged disease have been elucidated. |
| Session 19—Plenary |
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| 71 | AIDS RESTRICTION GENES: DISCOVERY, ASSESSMENT AND IMPLICATIONS Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no.71) Stephen O'Brian This presentation will describe the validity, attributes, and applications of these genes for the AIDS epidemic. In addition, further applications of ARGs based on selection signatures, mitochondrial DNA, and Y-chromosome influences will be described. Finally, a preview of a whole genome scan for undiscovered ARGs in the context of the recently annotated human Hap Map will be discussed. |
| Session 20—Oral Abstracts and Research Overview Neuropathogenesis: Viral Dynamics and Host Responses |
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| 72 | HIGH CEREBROSPINAL FLUID NEUROFILAMENT PROTEIN LEVELS IN AIDS DEMENTIA COMPLEX Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 72) Magnus Gisslén1, P Cinque2, L Hagberg1, R Price3, L Rosengren1, and B Brew4 The findings of this study support the value of CSF NFL as a useful marker of CNS damage in HIV infection. In patients without central nervous system opportunistic infections or tumors, elevated CSF NFL concentrations are associated with ADC, follow the grade of severity, and decrease after initiation of effective ART. Virtually all previously suggested CSF markers of ADC relate to immune activation or HIV viral load. NFL is the first marker that directly reflects brain injury; as such, CSF NFL levels should prove to be useful in clinical practice as an objective marker of ADC. |
| 73 | LEPTIN AND NEUROPSYCHOLOGICAL PERFORMANCE: A NEW BIOMARKER FOR COGNITIVE FUNCTION? Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 73) Jeannie Huang, S Letendre, J Beck, M Cherner, S Kolakowski, R Ellis, and HIV Neurobehavioral Res Group Decreased CSFL and CSLR are associated with neurocognitive deficits, specifically in memory and learning. Leptin may be important for memory and learning in humans, and may be useful as a clinical biomarker for neurocognitive function. |
| 74 | BETTER ANTIRETROVIRAL PENETRATION INTO THE CENTRAL NERVOUS SYSTEM IS ASSOCIATED WITH LOWER CSF VIRAL LOAD Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 74) Scott Letendre1, E Capparelli1, B Best1, D Clifford2, A Collier3, B Gelman4, J McArthur5, J McCutchan1, D Simpson6, R Ellis1, and the CHARTER Group These findings support that better penetration of ART across the blood-CSF barrier leads to better control of HIV replication in CSF. Since inhibition of HIV replication in the CNS is important in treating patients who have HIV-associated neurocognitive disorders, they may benefit from CNS-targeted ART therapy. |
| 75 | DISCORDANCE OF GENOTYPIC RESISTANCE BETWEEN CSF AND PLASMA VIRUS IN A MULTICENTER OBSERVATIONAL COHORT Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 75) Joseph Wong1,2, S Pillai1,2, R Ellis3, D Clifford4, A Collier5, B Gelman6, J McArthur7, J McCutchan3, S Morgello8, I Grant3, and the CHARTER Group Discordant resistance between CSF and plasma virus were frequently observed in this North American cohort in the absence of active CNS co-morbidities. These findings indicate that compartmentalization of HIV replication is not wholly dependent on variable ART penetration because classes of poorly penetrating ART (i.e., PI) did not differ from others, and because genetic distances between CSF and plasma virus sequences were at times large even in the absence of drug resistance mutations. The clinical implications of these findings remain to be determined. |
| 76 | THE HIV ENV N283 GENETIC VARIANT IS ASSOCIATED WITH BRAIN INFECTION AND DEMENTIA Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 76) Rebecca Dunfee1,2, E Thomas1,2, P Gorry1,2, J Taylor3, K Kunstman3, J Bell4, S Wolinsky3, and D Gabuzda1,2 The HIV env N283 genetic variant is associated with brain infection and HAD. N283 enhances macrophage and microglia tropism by increasing gp120-CD4 affinity through contact with Q40 of CD4. These results lead to a better understanding of mechanisms that underlie HIV neurotropism. |
| 77 | LONGITUDINAL ANALYSIS OF ENV POPULATION DYNAMICS IN BLOOD AND CEREBROSPINAL FLUID OF SIVsm-INFECTED MACAQUES Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 77) Patrick Harrington1, M Connell2, P Johnson2, R Meeker1, and R Swanstrom1 SIVsm populations are present in CSF early in infection, with no evidence of a genetic bottleneck for CSF invasion from the periphery. Furthermore, SIVsm populations in CSF can emerge and turn over rapidly. Even so few animals, we observed different relationships between the blood plasma and CSF viral populations over the course of infection: close concordance over a prolonged period of time versus rapid discordance. |
| 78 | HEMOCHROMATOSIS GENE POLYMORPHISMS AND PERIPHERAL NEUROPATHY DURING ART: ANALYSIS NWCS 238 OF ACTG STUDY 384 Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 78) Asha R. Kallianpur1, T Hulgan1, J Canter2, M Ritchie2, J Haines2, G Robbins3, R Shafer4, D Clifford5, D Haas1, and the AIDS Clin Trials Group Iron-loading HFE polymorphisms may be associated with a decreased risk of NRTI-associated peripheral neuropathy. This finding has potential implications for the prevention and management of NRTI-associated peripheral neuropathy, particularly among populations at risk for iron deficiency. Further study of functional mechanisms and confirmation of this association in other cohorts are warranted. |
| 79 | CONTROLLED STUDY OF HIGH-CONCENTRATION CAPSAICIN PATCH FOR PAINFUL HIV-ASSOCIATED DISTAL SENSORY POLYNEUROPATHY Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 79) David Simpson1, S Brown2, S Chang3, J Jermano3, and C107 Study Group This controlled trial in painful HIV DSP shows that CDP produces significant and durable pain reduction with good tolerability. CDP may provide a new mode of effective treatment for this disabling disease. |
| 80 | UPDATE ON SENSORY NEUROPATHIES Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 80) Justin McArthur Currently, there are no effective therapies for HIV-SN except for symptomatic control with anticonvulsants, selective antidepressants, or topical capsaicin (in high concentration). The hormone erythropoietin (EPO) prevents sensory axonal degeneration and in vitro neuronal death by both gp120 and ddC. EPO may be useful in the treatment of HIV-SN, and a controlled trial is underway. |
| Session 21—Oral Abstracts Hepatitis Viruses Complicating HIV Infection |
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| 81 | UTILITY OF THE EARLY VIRAL RESPONSE TO INDIVIDUALLY ADJUST THE DURATION OF TREATMENT FOR CHRONIC HEPATITIS C, GENOTYPE 2 OR 3, IN HIV-CO-INFECTED PATIENTS Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 81) Manel Crespo, J Esteban, E Ribera, V Falcó, A González, S Villar Del Saz, I Ocaña, and A Pahissa Early viral response appears as a useful tool to individually adjust the duration of treatment for chronic hepatitis C, genotype 2 or 3, in HIV-co-infected patients. In our study, high SVR and low viral relapse rates were observed after 24 weeks of therapy among those patients with undetectable viral load at week 4. |
| 82 | SERUM IP-10 LEVEL IS ASSOCIATED WITH DISTINCT EARLY VIRAL DYNAMICS IN HCV AND HCV/HIV-INFECTED SUBJECTS TREATED WITH IFN-α Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 82) Benigno Rodriguez1, H Valdez2, K Milkovich1, N Yonkers1, A Post3, R Bonomo3,4, D Bobak3, L Jones4, S Giulianetti4, and D Anthony1,4 HIV co-infection is associated with reduced 2-day HCV decline in pegIFN-treated subjects despite high initial IFN-α doses and serum IP-10 level increases consistent with a preserved downstream IFN-α effect. This suggests greater resistance to the effect of IFN-α2b in co-infected patients. IFN-γ HCV-specific responses are also diminished in co-infected patients, perhaps reflecting synergistic immune impairments due to both infections. Because relationships exist both between baseline serum IP-10 level and HCV level and between serum IP-10 increase and early HCV RNA decline, host IFN-α responsiveness at baseline may be predictive of IFN-α therapy virologic outcome. |
| 83 | EFFECTS OF CYTOKINE GENE POLYMORPHISMS ON TREATMENT OF ACUTE HEPATITIS C INFECTION IN HIV-INFECTED PATIENTS Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 83) Jacob Nattermann1, M Vogel1, G Ahlenstiel2, M Schulz1, T Sauerbruch1, U Spengler1, J Rockstroh1, and Kompetenznetz HIV/AIDS Response rates to interferon-alpha therapy are enhanced in acute HCV-infected HIV+ patients carrying the IL6 high producer genotype. This might be explained by the IL-6 mediated activation of signal transducers and activators of transcription (STAT), which have been shown to be essential for the antiviral effect of interferons and induction of anti-HCV activity in liver cells. |
| 84 | VIRUS-SPECIFIC T-CELL RESPONSES AND LOSS OF SPONTANEOUS CONTROL OF HCV IN HIV+ INDIVIDUALS Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 84) Arthur Kim, J Schulze Zur Wiesch, T Allen, R Gandhi, B Davis, A Jones, G Robbins, R Chung, G Lauer, and B Walker HIV-1-infected individuals with spontaneous control of HCV are at risk for recurrence of HCV viremia. This finding highlights the need for repeat viral load testing for controllers of HCV, particularly if coinfected, and provides a possible explanation for the higher rate of HCV persistence observed in this population. Our results also suggest that avoidance of low nadir CD4 counts may preserve memory lymphocytes against HCV that contribute to HCV control in coinfected persons. |
| 85 | ENHANCED REPLICATION OF GB VIRUS C IN HIV-INFECTED PATIENTS RECEIVING HAART Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 85) Per Björkman1, V Letelier Molnegren1, A Marshall1, L Flamholc1, N Güner2, and A Widell1 GBV-C viral load increases during HAART-induced suppression of HIV replication and decreases during treatment interruptions. This suggests that replication of GBV-C could be suppressed during progressive HIV infection, and supports the hypothesis that GBV-C RNA status may be secondary to HIV disease progression. |
| 86 | EVIDENCE FOR SEXUAL TRANSMISSION OF HCV IN RECENT EPIDEMIC IN HIV-INFECTED MEN IN THE UK Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 86) Mark Danta1, D Brown1, G Dusheiko1, O Pybus2, M Nelson3, M Fisher4, A Johnson1, C Sabin1, and S Bhagani5 High-risk and mucosally traumatic sexual factors are significantly associated with the recent transmission of HCV. The co-circulating HCV lineages identified by phylogenetic analysis belong to different subtypes and genotypes, indicating that the epidemic is not caused by viral genetic change, but rather patient factors such as sexual or drug behavior. These patient factors should be the focus of education-based public health interventions. |
| 87 | RISE IN HCV INCIDENCE IN HIV-INFECTED MEN WHO HAVE SEX WITH MEN IN AMSTERDAM: SEXUAL TRANSMISSION OF DIFFICULT TO TREAT HCV GENOTYPES 1 AND 4 Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 87) R Coutinho1 and Thijs van de Laar2 The incidence of HCV has significantly increased in HIV+ but not in HIV MSM in Amsterdam. The high degree of clustering observed in phylogenetic analysis provides strong evidence for the introduction and sexual transmission of different co-circulating HCV lineages. HIV infection and/or mucosal trauma caused by extreme sexual techniques and concurrent STD might facilitate sexual transmission of HCV. Increased incidence of mainly difficult to treat HCV genotypes 1 or 4 in HIV+ MSM might have serious implications for both individual and public health. |
| 88 | SYSTEMIC OVERVIEW OF HAART-ASSOCIATED LIVER ENZYME ELEVATIONS IN PATIENTS INFECTED WITH HIV AND CO-INFECTED WITH HCV Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 88) Yves Benhamou1, V Mats2, and D Walczak3 HIV co-infection but not baseline ALT is a strong predictor of HAART-related LEE. Among HIV-infected patients, the percentage of LEE increased as follows: NRTI<BPI<PI<NNRTI. The same order exists in HCV co-infected patients, but differences were not significant. |
| Session 22—Oral Abstracts and Research Overview Immunological Correlates of Protection: What Works and What Doesn't |
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| 91 | LACK OF NEUTRALIZING ANTIBODY RESPONSE TO HIV-1 PREDISPOSES TO SUPERINFECTION Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 91) Davey Smith1, M Strain2, S Frost1, S Pillai3, J Wong3, T Wrin4, C Petropoulos4, E Daar5,6, S Little1, and D Richman1,7 All 3 individuals identified with HIV superinfection had less cross-protective and autologous neutralizing antibody response than their non-superinfected case-controls. These data identify cross-protective neutralizing antibody in the prevention of superinfection and elucidate important goals for protective vaccine design. |
| 92 | BROAD NEUTRALIZATION OF HIV-1 VARIANTS IN COUPLES WITHOUT EVIDENCE OF SYSTEMIC SUPERINFECTION DESPITE EXPOSURE Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 92) J McConnell1, Y Liu2, C Kreis1, J Marcus1, L Bragg1, C Chappey2, E Stawiski2, T Wrin2, F Hecht3, and Robert Grant1 We observed development of broad neutralization activity during the first 2 years of infection, including activity against viruses in sexual partners. Broad serum neutralizing responses may be a mechanism that blocks superinfection in chronically infected couples and other highly exposed individuals. |
| 93 | NON-NEUTRALIZING ANTIBODY THAT PREVENTS SIV INFECTION IN NEONATAL RHESUS MACAQUES POTENTLY INHIBITS SIV IN THE PRESENCE OF RHESUS MACAQUE EFFECTOR CELLS Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 93) Donald Forthal1, G Landucci1, K Stefano Cole2, J Becerra1, M Marthas3, and K Van Rompay3 These results demonstrate, for the first time, that antibodies that do not neutralize pathogenic strains of SIV may nonetheless have potent anti-viral activity mediated by interactions between antibody Fc and Fc receptors on rhesus macaque cells, such as monocytes and natural killer cells. Since infusion of SIV-HIS prevents SIVmac251 infection in the absence of neutralizing activity, these results suggest that antibody-dependent, cell-mediated virus inhibition is a protective immune function against primate lentivirus infection. |
| 94 | SIMIAN IMMUNODEFICIENCY VIRUS ENGRAFTED WITH HIV-1-SPECIFIC EPITOPES: REPLICATION, NEUTRALIZATION, AND SURVEY OF HIV-1+ PLASMA Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 94) E Yuste1, H Sanford1, J Bixby1, S Little2, M Zwick3, T Greenough4, D Burton3, D Richman2,5, R Desrosiers1, and Welkin Johnson1 We have confirmed by direct analysis that neutralizing activities of the 2F5 and 4E10 specificities are either rare among HIV-1+ individuals or, if present, represent a small fraction of the total neutralizing activity in a given plasma sample. The parental SIV239 and neutralization-sensitive SIV316 control viruses were also not neutralized, indicating that significant cross-reactive neutralizing activity is not present in HIV+ patient plasma. Our results also suggest that the Env spikes of SIV239 and HIV-1 are structurally similar, and that resistance of SIV239 and HIV-1 primary isolates to antibody-mediated neutralization arises from similar mechanisms. |
| 95 | DEFINING AND MEASURING HIV-1 ESCAPE FROM CTL: EPITOPE-DEPENDENT AVIDITY THRESHOLDS Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 95) M Bennet, H Ng, A Ali, and Otto O. Yang These data indicate that the functional avidity required for the antiviral activity of HIV-1-specific CTL varies depending on the epitope. When assessing for viral escape due to epitope mutation the absolute change in avidity is not sufficient; the relationship of avidity to the KE50 better reflects whether CTL recognize the variant. Furthermore, greater avidity above the avidity threshold does not yield greater antiviral activity, consistent with the function of T-cell receptor binding as a simple trigger for CTL activity. |
| 96 | LOCALIZED POPULATIONS OF CD8- SIV-SPECIFIC T CELLS IN LYMPHOID FOLLICLES AND VAGINAL EPITHELIUM Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 96) Pamela Skinner1, T Mattila1, C White1, A Hage1, R Sunderman1, D Watkins2, C Miller3, E Connick4, and A Haase5 We hypothesize that antigen-specific CD8+ T cells down-modulate CD8 upon entering B-cell follicles or upon entering the epithelial layer of tissues in macaques, perhaps preventing unwanted cellular lysis and modulating immune activation in these specific tissue locations. Future studies are needed to determine whether this phenomenon also occurs during HIV and other infections. |
| 97 | MAINTENANCE OF HIV-SPECIFIC CD4+ T CELL HELP DISTINGUISHES HIV-2 FROM HIV-1 INFECTION Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 97) Melody Duvall1,2, A Jaye3, T Dong1, J Brenchley2, D Jeffries3, D Douek2, A McMichael1, H Whittle3, R Koup2, and S Rowland-Jones1,3 HIV-2-infected individuals with non-progressive disease mount a functionally superior HIV-specific CD4+ T cell response compared with HIV-1+ individuals or HIV-2+ progressors. This response is principally distinguished by a non-terminally differentiated, polyfunctional population of cytokine-producing cells with preserved proliferative capacity. In contrast to the diminished or absent HIV-1-specific CD4+ T cell response, a strong, functionally diverse, and heterogeneous HIV-2-specific CD4+ helper T cell response may be a contributing factor in the attenuated clinical phenotype of HIV-2 infection. |
| 98 | IMMUNE CONTROL OF HIV INFECTION: PREDICTABILITY IN THE MIDST OF CHAOS Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 98) Bruce Walker Using transmission pairs to control for the infecting virus, acute infection to control for duration of infection, and large population studies to control for viral and host genetic heterogeneity, it is clear that there is considerable predictability in the virus–host interaction, and that there are constraints on viral evolution under immune selection pressure. Such studies indicate that adaptive immune responses vary in their antiviral efficacy, and suggest that it may be possible to develop immunogens that represent the predictable variants that will arise under immune selection pressure. |
| Session 23—Oral Abstracts Antiretroviral Therapy II: New Insights and Treatment Strategies |
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| 101 | PREDICTORS OF HIV DISEASE PROGRESSION IN PATIENTS WHO STOP ART WITH CD4 CELL COUNTS >350 CELLS/mm3 Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 101) Daniel Skiest1, D Havlir2, R Coombs3, E Adams4, P Cain5, T Petersen6, D Rusin7, C Jennings8, K Robertson9, D Margolis9, and the ACTG 5170 Team ART interruption was generally safe in this cohort. Low nadir CD4 count is the best predictor of CD4 decline or clinical events following ART cessation. |
| 102 | CD4-GUIDED SCHEDULED TREATMENT INTERRUPTIONS COMPARED TO CONTINUOUS THERAPY: RESULTS OF THE STACCATO TRIAL Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 102) Jintanat Ananworanich1, A Gayet-Ageron2, M Le Braz2, W Prasithsirikul3, P Chetchotisakd4, S Kiertiburanakul5, P Phanuphak1, D Cooper6, K Ruxrungtham1, B Hirschel2, and the Staccato Study Group During 484 patient-years of STI, little evidence of treatment resistance emerged. Treatment-related adverse effects were more frequent in continuous therapy, but minor manifestations of HIV infection were more frequent in STI. |
| 103 | FINAL RESULTS OF A RANDOMIZED, CONTROLLED TRIAL OF STRUCTURED TREATMENT INTERRUPTIONS VS CONTINUOUS HAART IN CHRONIC HIV-INFECTED SUBJECTS WITH PERSISTENT SUPPRESSION OF VIRAL REPLICATION Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 103) Lucia Palmisano, M Giuliano, R Bucciardini, M Andreotti, V Fragola, C Galluzzo, M Pirillo, M Mancini, L Weimer, S Vella, and the Italian ISS PART Clin Ctrs Potential candidates to structured treatment interruptions are subjects with high pre-HAART CD4 count, absence of archived mutations, and residual replication <2.5 copies HIV RNA/mL. For this therapeutic strategy NNRTI-based regimens appear preferable to unboosted PI HAART. |
| 104 | STRUCTURED TREATMENT INTERRUPTIONS IN HIV-INFECTED PATIENTS WITH HIGH CD4 CELL COUNTS AND VIROLOGIC SUPPRESSION: RESULTS OF A PROSPECTIVE, RANDOMIZED, OPEN-LABEL TRIAL (WINDOW - ANRS 106) Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 104) Bruno Marchou1, P Tangre2, I Charreau2, J Izopet1, P M Girard3, T May4, J M Ragnaud5, J P Aboulker2, J M Molina6, and ANRS 106 Study Group In this population of patients, a fixed structured treatment interruption strategy of 8-weeks-off/8-weeks-on appeared clinically and immunologically safe over 96 weeks while sparing 48.5% of drug exposure. Patterns of drug resistance mutations in patients with virologic failure appeared similar. |
| 105LB | THE CD4-GUIDED STRATEGY ARM STOPPED IN A RANDOMIZED STRUCTURED TREATMENT INTERRUPTION TRIAL IN WEST-AFRICAN ADULTS: ANRS 1269 TRIVACAN TRIAL Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 105LB) Christine Danel1, R Moh1, S Sorho1, A Minga1, A Anzian1, O Ba-Gomis1, D Gabillard2, E Bissagnene1, R Salamon2, X Anglaret2, and ANRS 1269 Study Group CGT led to a 2-fold higher serious morbidity rate than CT, mainly due to invasive bacterial diseases. Further structured treatment interruption trials assessing CGT strategies in sub-Saharan Africa should use higher CD4 thresholds for interruption/introduction. Whether a fixed treatment-interruption strategy is appropriate in Côte d’Ivoire requires further follow-up. |
| 106LB | EPISODIC CD4-GUIDED USE OF ART IS INFERIOR TO CONTINUOUS THERAPY: RESULTS OF THE SMART STUDY Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 106LB) Wafaa El-Sadr and J Neaton for the SMART Study Investigators SMART, a large international trial, demonstrated that CD4-guided episodic ART use aimed at maintaining CD4 >250 cells/mm3 is associated with increased short-term risk of progression of HIV disease and death compared to continuous ART. |
| 107LB | EFFICACY AND SAFETY OF ATAZANAVIR-BASED THERAPY IN ANTIRETROVIRAL NAÏVE HIV-1 INFECTED SUBJECTS, BOTH WITH AND WITHOUT RITONAVIR: 48-WEEK RESULTS FROM AI424-089 Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 107LB) Niel Malan1, E Krantz2, N David3, K Kastango4, D Frederick4, M Matthew4, S Schnittman4, J Hammond4, and the -089 Study Group In this study in ART-naïve HIV+subjects, ATV, with or without RTV, demonstrated a high rate of virologic response through 48 weeks. Both arms were generally safe and well tolerated, although subjects on ATV/r had a higher rate of hyperbilirubinemia. These results support additional studies using ATV/r in ART-naïve subjects. |
| 108LB | A PROSPECTIVE, OPEN-LABEL, PILOT TRIAL OF REGIMEN SIMPLIFICATION TO ATAZANAVIR/RITONAVIR ALONE AS MAINTENANCE ANTIRETROVIRAL THERAPY AFTER SUSTAINED VIROLOGIC SUPPRESSION (ACTG 5201) Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 108LB) Susan Swindells1, T Wilkin2, G DiRienzo3, C Fletcher4, G Thal5, H Huang3, E Werner4, J McKinnon6, J Mellors6, and the AIDS Clin Trials Group Simplified maintenance therapy with ATV/RTV alone appears safe and effective through 24 weeks. Virologic failure occurred in 3 of 34 subjects, 2 of whom had undetectable plasma ATV concentrations. Resistance to PI was not detected at virologic failure. Larger, randomized trials are now warranted to define further the efficacy of this strategy. |
| 109LB | SAFETY OF NEVIRAPINE COMPARED TO ABACAVIR ON A BACKGROUND OF ZIDOVUDINE/LAMIVUDINE AS FIRST-LINE ANTIRETROVIRAL THERAPY: A RANDOMIZED DOUBLE-BLIND TRIAL Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 109LB) Paula Munderi and the DART Trial Team Compared with NVP, ABC had a lower discontinuation rate and a trend toward a lower rate of serious adverse reactions in African patients initiating ART with low CD4 counts. With the possible exception of hepatotoxicity, there was considerable overlap in the clinical manifestations of reactions to ABC and NVP in this population. |
| 110 | VIRAL DECAY RATES IN MEN AND WOMEN RECEIVING TRIPLE-NUCLEOSIDE OR EFAVIRENZ-CONTAINING ART: VIRAL DYNAMICS SUBSTUDY OF ACTG A5095 Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 110) Kathleen Squires1, H Ribaudo2, D Kuritzkes3, C Shikuma4, W Meyer5, K Klingman6, R Gulick7, and ACTG A5166s and ACTG A5095 First phase viral decay rates were significantly faster in patients receiving ZDV/3TC+EFV compared with a triple NRTI regimen; no other treatment differences in first or second phase viral decay rates were seen. There were no differences in viral decay rates between men and women. |
| Session 27—Symposium What's New in Vaccines: The Membrane Proximal Region of HIV Envelope and Its Role as a Target of Broadly Neutralizing Antibodies |
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| 111 | IN VITRO AFFINITY MATURATION OF THE HIV-1 BROADLY NEUTRALIZING ANTI-gp41 ANTIBODY Z13 Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 111) Michael Zwick, J Nelson, F Brunel, R Cardoso, I Wilson, P Dawson, and D Burton Our structure-function analysis of peptides specific for Z13e1 and 4E10 has provided new insights into the cognate epitopes on the MPER of gp41 and may be helpful in structure-based vaccine design. Finally, a whole IgG Z13e1 has been engineered and neutralization behavior and potential autoreactivity are being investigated. |
| 112 | POTENTIAL DIFFICULTIES IN ELICITING ANTIBODIES TO THE MEMBRANE PROXIMAL REGION OF HIV-1 Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 112) Barton Haynes, L Verkoczy, A Moody, G Kelsoe, and A Alam These findings have raised the hypothesis that some species of broadly neutralizing antibodies may not be readily made because they are subjected to negative B cell immunoregulatory control. A related hypothesis proposes that animals or patients with defects in B cell tolerance under certain circumstances will be able to make 2F5 and 4E10-like antibodies that neutralize HIV-1. We will discuss strategies to test these hypotheses, and present data from studies in animals regarding analysis of origin of anti-MPER B cells. |
| 113 | THE MEMBRANE PROXIMAL EXTERNAL REGION OF HIV-1 ON DIFFERENT VIRAL SCAFFOLDS: DETECTION OF EPITOPE-SPECIFIC NEUTRALIZING ANTIBODIES Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 113) F Bibollet-Ruche1, J Decker1,2, H Li1, P Goepfert1, M Peeters3, S Allen4, E Hunter4, J Robinson5, P Kwong6, and George M Shaw1,2 These results indicate that the MPER of HIV-1 is inherently immunogenic and elicits neutralizing antibody responses in a substantial proportion of infected patients. Epitopes recognized by these neutralizing antibodies are distinct from those recognized by 4E10 or 2F5. |
| 114 | LESSONS FROM THE USE OF MEMBRANE PROXIMAL EXTERNAL REGION ANTIBODIES IN VIVO Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 114) Alexandra Trkola, A Manrique, P Rusert, B Joos, M Fischer, M Huber, H Kuster, and H Gunthard Viruses preserved sensitivity to the MPER monoclonal antibodies 2F5 and 4E10 in vivo despite the ability of the tested viral isolates to tolerate mutations in the epitope of these antibodies in vitro. Collectively these data suggest, that in vivo dosing or distribution of 2F5 and 4E10 to the relevant sites of viral replication was too low to exert immune selection or alternatively, that in vivo selection pressures against the generation of such mutants exist. |
| Session 28—Symposium Almost 20 Years of Antiretroviral Therapy: Still a Lot to Learn |
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| 115 | IMPLICATIONS OF EARLY EVENTS IN HIV INFECTION FOR TREATMENT: BACK TO THE FUTURE? Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 115) Jeff Lifson While the potential benefits of effective, non-toxic treatment aggressively implemented during primary infection appear considerable, and such approaches should continue to be studied as new treatments are developed, experience with currently available drug regimens does not seem to support early treatment as a standard of care. |
| 116 | IS HIV A FEMINIST? SEX DIFFERENCES IN OUTCOMES ON HAART Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 116) Monica Gandhi Given the racial and ethnic mix of HIV among women in the United States, and the overwhelming burden of infection in specific regions around the globe, this variability needs further study in population pharmacokinetic models, especially those that incorporate pharmacogenomic parameters. Finally, psychosocial factors play a role in sex-based differences in the HAART era, including effects on adherence and access to therapy. This talk will summarize the studies to date that have examined sex disparities in outcomes on HAART over the last 10 years. The focus of this discussion will be entirely on sex differences in responses to ART and will not review the literature on sex disparities in HIV infection prior to the HAART era. Although a number of investigations have specifically looked at sex differences in outcomes on HAART, a number of opportunities have been missed to recruit more women into HIV clinical trials to stratify and analyze outcomes by sex. As we approach the 20-year mark for ART, we require a greater mandate to conduct studies on sex disparities in HAART outcomes to optimize therapy for an increasingly feminized epidemic. |
| 117 | LIMITING THE LIMITATIONS OF ANTIRETROVIRALS Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 117) Andrew Carr This presentation will focus on the diagnosis and potential management strategies for these toxicities. |
| 118 | NEW AGENTS AND TREATMENT PARADIGMS: NAVIGATING THROUGH THE DRUG DEVELOPMENT MINE FIELD Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 118) Michael Saag This will review the process of drug discovery, illustrated with examples of exhilarating successes and disappointing failures, with a focus on the current status of new drug development and its potential impact on the future of clinical practice, including the cost of care, for HIV patients worldwide. |
| Session 31—Plenary |
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| 120 | CIRCUMCISION AND HIV TRANSMISSION: THE CUTTING EDGE Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 120) Thomas C Quinn These epidemiologic, biological, and clinical trial results provide strong evidence that male circumcision significantly lowers the risk of HIV acquisition. Mathematical models of implementing male circumcision in countries with high incident rates suggest marked reductions in HIV incidence in men with subsequent decreased transmission rates to women. Policy implications of recommending male circumcision to populations in high-risk countries need to take into consideration cultural norms, religious traditions, national and local laws. Circumcision may represent one important biological intervention to decreasing the acquisition of HIV, but will need to be carefully integrated into other HIV prevention and sexually transmitted disease control programs prevent subsequent behavioral disinhibition among circumcised men. |
| Session 32—Plenary |
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| 121 | PREVENTING HIV TRANSMISSION BY TOPICAL MICROBICIDES Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 121) John Moore A practical microbicide product must not only be effective, but must also be safe, affordable, and acceptable to the user. Some, or all, microbicides will have to overcome various obstacles if they are eventually to be developed as products for men and women to use. |
| Session 33—Oral Abstracts Mother-to-Child Transmission and HIV in Women |
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| 122LB | EVIDENCE FOR PERSISTENT, OCCULT INFECTION IN NEONATAL MACAQUES FOLLOWING PERINATAL TRANSMISSION OF SHIV-SF162P3 Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 122LB) Nancy Haigwood1,2, L Misher1, C Ng2, T Zhu2, L Kuller3, P Polacino3, H Bielefelt-Ohmann3, D Mohan1, S L Hu2,3, and P Jayaraman1,2 Mechanisms accounting for low-level viral persistence in these neonates are presently unclear. A minority of adults exposed repeatedly to HIV can remain seronegative; in some cases these exposed seronegative individuals have HIV-1 DNA persisting in resting CD4+ T cells at levels below the detection limit of conventional PCR assays. Maternal IgG could contribute to rapid viral control, although at least some of the infant transmitted envs in pseudotyped virus are resistant to maternal neutralizing antibodies. Understanding the control of SHIV infection in newborn macaques at such low levels has implications for lentiviral pathogenesis and potential vaccine strategies to limit breast-milk transmission. |
| 123 | IDENTIFICATION OF A HUMAN MILK GLYCOPROTEIN THAT BINDS DC-SIGN AND INHIBITS HIV-1 TRANSFER TO CD+ T LYMPHOCYTES Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 23) Marloes Naarding1, A Dirac2, D Speijer1, G Pollakis1, and W Paxton1 We have identified a specific glycoprotein in human milk that binds to DC-SIGN and can inhibit HIV-1 transfer to CD4+ T lymphocytes. Identification of this molecule may provide for a better understanding of mother-to-child transmission of HIV-1 via breastfeeding and provide a further target for future microbicide development. |
| 124 | EVIDENCE FOR DISTINCT MECHANISMS FOR INTRAUTERINE AND INTRAPARTUM HIV MOTHER-TO-CHILD TRANSMISSION Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 124) Elizabeth Russell1, J Kwiek1, V Mwapasa2, M Malyneux3, S Rogerson4, R Swanstrom5, and S Meshnick1 Intrauterine and intrapartum appear to represent distinct mechanisms of transmission. Intrauterine transmission represents a greater bottleneck but involves transmission of the predominantly circulating virus. Intrapartum transmission represents less of a bottleneck but often involves the transmission of rare variants that are either compartmentalized in the mother or highly selected. |
| 125 | EFFECTIVENESS OF REPEAT SINGLE-DOSE NEVIRAPINE IN SUBSEQUENT PREGNANCIES AMONG UGANDAN WOMEN Conf Retroviruses Opportunistic Infect 2006 Feb 5-8;13: (abstract no. 125) C Eure1, Paul Bakaki2, M McConnell1, M Mubiru2, M Thigpen1, P Musoke2, F Mmiro2, M Fowler2, and the MUJHU NVP Resistance Group Based on both retrospective and prospective data including women from the HIVNET 012 trial, no increased risk of infant HIV infection was noted in subsequent pregnancies for Ugandan women with prior sdNPV exposure compared to NVP-naïve women. |
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