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1st International AIDS Society Conference on HIV Pathogenesis and TreatmentBuenos Aires, Argentina - July 8-11, 2001 |
| Plenary Lectures | |
| PL1. | LEARNING BASIC SCIENCE FROM CLINICAL TRIALS David D. Ho Aaron Diamond AIDS Research Center, The Rockefeller University, New York, USA. Abstract: First, the virus can lay dormant within resting memory CD4 T cells, creating a latent reservoir that decays slowly during treatment with currently available drug regimens. Second, recent experiments show that HIV replication has not been completely stopped, and the virus continues to replicate despite undetectable viremia. Attempting to overcome these obstacles, we have designed and tested a new drug regimen (lopinavir/ritonavir, efavirenz, lamivudine and tenofovir) that has resulted in a substantially faster decay of plasma viremia in treated individuals. These new data suggest that the potency of current antiretroviral regimens could be improved significantly. |
| PL2. | CURRENT CONTROVERSIES IN ANTIRETROVIRAL AND POTENTIAL SOLUTION: TRANSLATING SCIENCE INTO ACTION. Julio S. Abstract: Taken together these developments suggest that further optimization of antiretroviral therapy may be achieved by strategic targeting of such programs, as well as optimizing their safety. It should be stressed, however, that with the increasing complexity of HIV management the success of such programs will be highly dependant on the development of appropriate infrastructure, specifically including adherence support for HIV infected individuals and ongoing treatment and education for their treaters. |
| PL3. | FOSTERING ACCESS TO HIV/AIDS CARE AND TREATMENT Vella, S. Abstract: The International Fund should also be used to provide antiretroviral drugs to the South of the world. However, it is a serious mistake to think that provision of the drugs alone will be enough to solve the crisis. Even with radical price reductions, millions of poor people will still lack access to HIV treatment if adequate health services infrastructure is not available. Provision of antiretrovirals need to be accompanied by resources for counselling and testing, drug distribution, education and training of health care providers, development of treatment protocols, and monitoring. In summary, it would require strengthening of the local health care infrastructure, which subsequently could have a major positive impact on other diseases affecting these countries. Science should play an important role, by re-orienting research efforts towards the South. Particularly, through the development of new safe, effective and cheap drugs, microbicides and vaccines, and through the exploration of new treatment strategies such as immune interventions, pulsed or intermittent treatments, and easier monitoring systems. |
| PL4. | HOST FACTORS IN THE PATHOGENESIS OF HIV DISEASE: IMPLICATIONS FOR THERAPEUTIC STRATEGIES Anthony S. Fauci, M.D. Abstract: Therefore, a number of approaches that may reduce a patient's reliance on HAART are being pursued for the long-term control of HIV disease. Among these are variations on the theme of strategically interrupting therapy. In acutely infected individuals, recent data indicate that strategic therapy interruptions are associated with a likely enhancement of the immunological responses that could control viremia. With chronically infected individuals, who may have substantial immune system damage, the situation is somewhat different. In this patient group, a number of structured therapy interruption protocols have focused on the concept of allowing the virus to rebound and "autoimmunize" against the virus, thereby enhancing the immune system. Generally these protocols resume therapy after interruption only when plasma virus rises to pre-determined levels. We have taken a somewhat different approach, in which patients discontinue and resume therapy at pre-determined times: either two months on therapy followed by one month off; or seven days on therapy followed by seven days off. |
| PL5. | MOLECULAR RETROVIROLOGY: VIRAL LIFE CYCLE AND REGULATORY GENES. Bryan R. Cullen Abstract: In contrast to Tat, Rev acts at the posttranscriptional level and is essential for the nuclear export, and hence translation, of late viral mRNA species. Rev binds to these RNAs, via an RNA target termed the RRE, and also to a cellular factor termed Crm1, which mediates the actual RNA export. Recently, we have been able to construct an entirely synthetic Rev-like nuclear export factor that consists of a bacterial RNA binding domain linked to an heterologous Crm1 binding domain. The finding that this synthetic protein can fully substitute for Rev demonstrates that Crm1 recruitment is the sole function of HIV-1 Rev. Therefore, both Tat and Rev serve simply to target pre-existing cellular factors to novel RNA target sites present in the HIV-1 genome. |
| PL6. | HIV: TWENTY YEARS AFTER THE DISCOVERY OF THE AIDS EPIDEMIC Barre-Sinoussi, F Abstract: Not submitted. |
| Oral Sessions | |
| Session 1, Oral: Clinical Trials 1 Monday, July 9th |
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| 1. | NNRTIS vs. PIS: WITH WHAT TO START THERAPY Clotet, B Abstract: For patients with very low CD4 cell count (< 100/mm³) and high viral loads (VL> 100,000 copies/ml) an approach with a high genetic barrier (PI based HAART) could be better as a first line treatment than an NNRTIs based ARV therapy (low genetic barrier). The risk for subsequent development of lypodistrophy (LD) depends on the prolonged use of NRTIs associated to PIs. Some specific NRTIs and PIs may produce a higher incidence of fat redistribution and/or lipoatrophy. Proper use of these drugs and selection of those associated with a lower risk of LD may reduce significantly this adverse effect. Subsequent switch of the PI by an NNRTI may reduced further the risk of lypodistrophy. Some PIs do not produce severe dislipemia while some NNRTIs may be associated with significant changes in the lipid metabolism. Additional issues like cross-resistance, viral fitness, local prevalence of primary resistances, long-tern toxicities should also be taken into consideration for selecting the first choice. |
| 2. | ANTIVIRAL ACTIVITY, SAFETY AND PHARMACOKINETICS OF MOZENAVIR(DMP 450), A NOVEL CYCLIC UREA PROTEASE INHIBITOR, IN COMBINATION WITH D4T AND 3TC IN TREATMENT-NAÏVE HIV-1 INFECTED PATIENTS(STUDY DMP-102) Sierra-Madero, J. Abstract: The 24 Week data show that all three doses of mozenavir produced significant antiviral activity comparable to that of indinavir. The safety analyses show good tolerability and safety for all doses tested with no difference noted in regards to effects on cardiac repolarization. |
| 3. | SAFETY AND EFFICACY OF TIPRANAVIR, A NON-PEPTIDIC PROTEASE INHIBITOR, IN MULTIPLE PI-FAILURE PATIENTS (BI 1182.2) Curry R, Markowitz M, Slater L, Neubacher D, Robinson P, Cotton G, BI 1182.2 STUDY TEAM Abstract: Both dose regimens of TPV and low dose RTV plus EFV and 1 new NRTI were well tolerated and demonstrated durable, potent antiviral activity in a population of patients with multiple PI failure. |
| 4. | A RANDOMISED, OPEN LABEL STUDY TO INVESTIGATE ABACAVIR ( ABC) AND LAMIVUDINE ( 3TC) AS ONCE DAILY (QD) COMPONENTS OF A TRIPLE COMBINATION REGIMEN (EPV40001). Bowonwatanuwong C, Mootsikapun P, Supparatpinyo K, Tansuphaswadikul S, Athisegran R, Pasook P, Jones A Abstract: In this pilot study, both 3TC QD and ABC QD were effective as components of HAART. Both 3TC and ABC warrant further investigation as components of complete once daily regimens. |
| 5. | PHASE II 24-WEEK DATA FROM STUDY AI424-008: COMPARATIVE RESULTS OF BMS-232632, STAVUDINE, LAMUVIDINE AS HAART FOR TREATMENT-NAÏVE HIV-INFECTED PATIENTS Cahn P, Percival L, Phanuphak P, Sanne I, Kelleher T, Giordano M Abstract: BMS-232632 is safe and well-tolerated and associated with substantially lower concentrations in the serum lipids known to increase cardiovascular risk. The unblinded 24-week results, including efficacy (proportion <50 c/mL and <400 c/mL, and CD4), tolerability and safety will be reported. |
| 6. | KALETRA VS. NELFINAVIR IN ANTIRETROVIRAL-NAÏVE SUBJECTS: WEEK 60 COMPARISON IN A PHASE III, BLINDED, RANDOMIZED CLINICAL TRIAL Ruane P, Mendonca J, Timerman A, Cernohous P, Bauer E, Bernstein B, Sun E Abstract: A significantly greater proportion of LPV/r-treated subjects achieved HIV RNA <400 copies/mL and <50 copies/mL at Week 60. Both regimens were well tolerated, as manifested by the low incidence of study drug-related discontinuations through Week 60. |
| 7. | FINAL 12-MONTH RESULTS FROM THE COMBINE STUDY: A RANDOMIZED, OPEN, MULTICENTER TRIAL COMPARING COMBIVIR PLUS NELFINAVIR OR NEVIRAPINE IN NAÏVE PATIENTS Podzamczer D, Ferrer E, Consiglio E, Gatell J, Perez P, Perez J, Luna E, González A, Pedrol E, Lozano L Abstract: Our results suggest that CNr has at least similar efficacy than a protease inhibitor-containing regimen of CNf. Both regimens have an acceptable tolerance. A simple 4-pill CNr regimen may be an excellent option for HIV-infected pts who initiate antiretroviral therapy. |
| Session 2, Oral: Vaccine Development Monday, July 9th |
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| 8. | IMMUNOLOGICAL BASIS FOR HIV VACCINE DEVELOPMENT Jorge Flores Abstract: While non-human primate models have been successfully employed in evaluating vaccine candidates, understanding correlates of protection and streamlining the number of candidates entering clinical trials, the evaluation of vaccine efficacy will ultimately require large clinical trials in which immunological and virological correlates of immunity are examined at the same time that protection from infection or amelioration of disease are assessed. |
| 9. | ANTIBODY PROTECTION OF MACAQUES AGAINST VAGINAL CHALLENGE WITH A PATHOGENIC R5 HIV-1/SIV CHIMERIC VIRUS REQUIRES COMPLETE NEUTRALIZATION OF VIRUS Parren P, Marx P, Luckay A, Harouse J, Cheng-Mayer C, Moore J, Burton D Abstract: A major unknown in human immunodeficiency virus (HIV-1) vaccine design is the efficacy of antibodies in preventing mucosal transmission of R5 viruses. These viruses, which use CCR5 as coreceptor, appear to be crucial in transmission of HIV-1 in humans. |
| 10. | IMMUNOGENICITY AND PROTECTIVE EFFICACY OF A PRIME BOOST STRATEGY USING DNA-MVA HIV/SIV VACCINES IN MACAQUES Biberfeld G, Mäkitalo B, Sutter G, Ten Haaft P, Wahren B, Thorstensson R Abstract: To investigate the immunogenicity and protective efficacy of a prime boost strategy using DNA-MVA HIV/SIV vaccines were explored in cynomolgus monkeys. |
| 11. | IDENTIFICATION OF HIV-SPECIFIC CD4+ T CELLS IN PERIPHERAL BLOOD OF HIV-1- INFECTED INDIVIDUALS BY TETRAMERIC HLA-DR MOLECULES COVALENTLY COMPLEXED WITH PEPTIDES. Yassine Diab B, Younes S, Breton G, Macdonald K, Routy J, Connors M, Sekaly R Abstract: Previous reports have demonstrated the presence of potent HIV-specific responses in primary HIV infection (PI), which were maintained either in long-term non-progressors (LTNP) or in individuals treated with highly active anti-retroviral therapy (HAART). The major goals of this work were to characterize the origin of HIV-specific CD4+ T cells and to identify their role in disease progression. |
| 12. | TOWARDS A MOLECULAR UNDERSTANDING OF THE BROAD NEUTRALIZING ACTIVITY OF THE HUMAN ANTI-GP120 ANTIBODY B12 Zwick M, Ollmann Saphire E, Pantophlet R, Dawson P, Wilson I, Parren P, Burton D Abstract: The human monoclonal antibody (mAb) b12 potently neutralizes a broad range of primary isolates of HIV-1. |
| 13. | ENHANCED EFFICACY OF VLP BASED DNA PRIME/PROTEIN BOOST IMMUNIZATION OF MACAQUES AGAINST PATHOGENIC SIMIAN IMMUNODEFICIENCY VIRUS (SIV) USING IL-12 AND GM-CSF ADJUVANTS Kraiselburd E, Martinez I, Israel Z, Sidhu M, Villinger F, Montefiori D, Stout R Abstract: Our studies investigated the potential for VecB7, a SIVsm DNA-based vaccine that produces virus-like particles (VLP) in vitro, to induce protective responses in rhesus macaques using a DNA prime/protein boost strategy. |
| 14. | REVERSION KINETICS OF A LIVE ATTENUATED SIV CAN BE IMPAIRED BY THE M184V MUTATION IN THE SIV RT Whitney J Abstract: The development of an effective HIV vaccine has presented a considerable challenge. Towards this end a significant number of SIV based models have already been developed, most employing deletion of viral accessory genes. In contrast to these approaches our lab has developed a set of novel attenuated SIV mac candidates containing deletions within the 5 region of the leader sequence. These constructs displayed marked attenuation in cell lines and monkey PBMCs. |
| Session 3, Oral: Immunological & Virological Markers of Outcome Monday, July 9th |
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| 15. | MODELLING OF LONG TERM TREATMENT RESPONSES Professor B G Gazzard MA MD FRCP Abstract: As effective treatment for HIV treatment has only developed recently and is rapidly evolving, it is not surprising there are no studies yet published to guide optimum long term strategic drug treatment. In the absence of such sub-studies mathematical analysis using mark-off models are useful in understanding the importance of some of the issues involved and can help to guide health economic analysis, optimum time to initiate treatment and best first treatment options. Much of this work has been pioneered by Dr Pablo Tebas who has demonstrated that later initiation of treatment may be associated with a better long term outcome and reduced drug resistance. He has also suggested that the intuitive initiation with the most potent antiretroviral regime may not provide the best long term outcome if such treatments are not durable or tend in failure to allow virus to reappear in the circulation which does not respond well to the second regime. Using similar models, cost effectiveness analysis has indicated that antiretroviral therapies are amongst the most effective and cheapest treatments for chronic diseases and that even in some of the developing world, such therapies should be seriously considered as a viable option. |
| 16. | VIRAL LOAD, PERCENTAGE CD4 CELL COUNT AND SURVIVAL IN HIV MONOTYPIC AND DUAL INFECTIONS IN WEST AFRICA Alabi S, Blanchard T, Shabbar J, Corrah T, Ariyoshi K, Berry N, Whittle H Abstract: Both plasma viraemia and CD4% were independently associated with survival in HIV-2 infection, while only CD4% was independently associated with survival in HIV-1 and in dual infections. After adjusting for plasma viraemia and CD4%, survival in HIV-1 or HIV-2 infected individuals did not differ significantly. Our findings give new insight into how these two viruses differ; and may provide the means with which patients are better counselled about their prognosis, and by which therapies might be tested and monitored. |
| 17. | CLINICAL COURSE OF HIV-INFECTED PATIENTS WITH DETECTABLE VIREMIA WHILE ON ANTIRETROVIRAL THERAPY Tenorio A, Smith K, Sha B, Kuritzkes D, Landay A, Kessler H Abstract: To characterize the clinical, immunologic and virologic course of HIV-infected patients on antiretroviral therapy (ART) with stable detectable viremia (viral load or VL: 50-10,000 copies/ml) for > 6 months (plateau subjects or P). |
| 18. | QUANTIFYING 'PARADOXICAL' CD4 RESPONSES AMONG A CLOSELY FOLLOWED COHORT OF PATIENTS INITIATING ANTIRETROVIRAL THERAPY Wood E, Yip B, Hogg R, Sherlock C, Harrigan R, O'shaughnessy M, Montaner J Abstract: We have characterized pVL and CD4 cell responses in a closely followed cohort of patients initiating triple drug therapy to evaluate determinants and prevalence of ‘discordant’ CD4 responses |
| 19. | IMMUNE ACTIVATION IS A MAJOR CAUSE FOR CD4 DECLINE DURING HIV INFECTION;BETTER CORRELATION OF IMMUNE ACTIVATION MARKERS THAN HIV PLASMA VIRAL LOAD TO CD4 LEVELS Bentwich Z, Kalinkovich S, Leng Q, Weissman Z, Borkow G Abstract: Study the role of T-cell immune activation and proliferation and HIV-1 plasma viral load (VL) in determining CD4+ T-cell levels during HIV-1 infection. |
| 20. | CCR5 HAPLOTYPES ASSOCIATED WITH ALTERED RATES OF HIV-1 VERTICAL TRANSMISSION AND PROGRESSION TO DISEASE IN CHILDREN Mangano A, Gonzalez E, Catano G, Bologna R, Ahuja S, Sen L Abstract: Genetic variation in CC chemokine receptor 5 (CCR5), the major coreceptor for HIV-1 cell entry, has been associated with differences in susceptibility to infection as well as disease progression. The aim of this study was to determine the contribution of CCR5 genotypes in HIV-1 mother-to-child transmission and progression to AIDS in infected children. |
| Session 4, Oral: Viral Reservoires Monday, July 9th |
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| 21. | IN PATIENTS ON PROLONGED HAART, A SIGNIFICANT PART OF HIV-INFECTED CD4 T CELLS ARE SPECIFIC OF HIV ANTIGENS Taoufik Y, Demoustier A, Lambotte O, Degoer M, Wallon C, Goujard C, Delfraissy J Abstract: HAART allows the reduction of plasma HIV RNA to undetectable levels for prolonged periods in many patients. |
| 22. | THE RECTAL MUCOSA IS A SITE OF HIV-1 REPLICATION AND SHEDDING AND CD4+ T-CELL DEPLETION IN MEN WITH CHRONIC HIV-1 INFECTION Tabet S, Brodie S, Dondero D, Haggitt R, Huang M, Kelly C, Celum C Abstract: The GI tract is an early site of HIV/SIV replication and associated with marked CD4+ T cell depletion, yet data is limited in chronic HIV infection. |
| 23. | EARLY HIV-1 DNA LEVEL PREDICTS DISEASE PROGRESSION AND DEATH INDEPENDENTLY OF HIV-RNA LEVEL AND CD4 CELL COUNT Rouzioux C Abstract: HIV DNA is the best predictor of disease progression; it should help on the difficult decision when to start antiretroviral therapy. |
| 24. | PERSISTENCE OF LOW-GRADE HIV-1 REPLICATION IN RESTING MEMORY T CELLS IN PERSONS INITIATING EARLY AND AGGRESIVE ANTIRETROVIRAL THERAPY Brodie S, Berrey M, Patterson B, Mullins J, Stevenson M, Corey L Abstract: Early combination antiretroviral therapy may preserve HIV-1-suppressive mechanisms important in the containment of viral replication following the interruption of therapy. |
| 25. | MONITORING INTRACELLULAR HIV1 REPLICATION IN BLOOD AND LYMPHOID TISSUE IN ANTIRETROVIRAL NAÏVE SUBJECTS RECEIVING AMPRENAVIR (APV), ABACAVIR (ABC), AND 3TC (COLA3003 STUDY) Patterson B, Becker S, Snidow J, Pobiner B, Landay A Abstract: This regimen results in less persistent viral replication in peripheral blood. Macrophages may represent a relatively resistant cellular reservoir during HAART therapy necessitating cell-specific viral load monitoring and cell-specific antiretroviral therapy. |
| 26. | PERSISTENT DEPLETION OF CD4 + T CELLS IN LYMPHOID TISSUES AMONG PATIENTS RANDOMIZED TO TRIPLE NUCLEOSIDE VS. PROTEASE OR NONNUCLEOSIDE CONTAINING REGIMENS IN THE ATLANTIC STUDY Schacker T, Ngyuen P, Gatell J, Horban A, Berzins B, Lange J, Murphy R Abstract : Standard combinations of drugs for HIV therapy include 2 nucleoside analogues (NA) + 1 protease inhibitor (PI) or 2 NA + 1 non-nucleoside analogue (NNA) and recently regimens of 3 NA have been recommended. |
| 27. | DISCREPANCIES BETWEEN VIRAL LOAD, RESISTANCE PROFILE AND PROTEASE INHIBITORS' CONCENTRATION IN HIV-1 RESERVOIRS AND SANCTUARIES Chadapaud S, Hittinger G, Solas C, Halfon P, Khiri H, Lacarelle B, Lafeuillade A Abstract: To assess viral load, genotypic resistance and protease inhibitors’(PI) diffusion in viral reservoirs and sanctuaries during highly active antiretroviral therapy (HAART). |
| 28. | VIROLOGICAL RESPONSE IN RESERVOIRS IN HIV-INFECTED NAÏVE PATIENTS TREATED WITH COMBIVIR PLUS NELFINAVIR (CNF) OR NEVIRAPINE (CNR) Ferrer E, Podzamczer D, Perez P, Perez J, Estela J, Maños M, Lozano L, Sole R, Martínez - La Casa J, Casado A Abstract: Both CNf and CNr achieve a virological response in reservoirs. However, anti HIV-1 activity may be suboptimal in lymphoid tissue, at least in some pts. The long term clinical significance of a rebound in HIV-1 RNA in LT and not in plasma is unclear. |
| Session 5, Oral: Treatment Strategies Monday, July 9th |
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| 29. | STRUCTURED TREATMENT INTERRUPTIONS (STIS) Diane V. Havlir Abstract: STIs are also being evaluated as a means to reduce pill burden and drug toxicity. In areas with limited resources, such strategies offer the possibility of increasing ARV access. The optimal timing and duration of STIs in these patients are not known. "Flexible" schedules which trigger re-institution of therapy for either a CD4 , an HIV RNA threshold or both represent one strategy. "Fixed" schedules designating duration of STI represent an alternate approach. Risks of STIs for these patients include drug resistance, repopoulation of HIV reservoirs that were gradually diminishing, and subtle effects on quality of life including cognitive function. |
| 30. | THERAPEUTIC DRUG MONITORING (TDM) OF NELFINAVIR (NFV) AND INDINAVIR (IDV) IN TREATMENT-NAÏVE PATIENTS IMPROVES THERAPEUTIC OUTCOME AFTER 1 YEAR: RESULTS FROM ATHENA Burger D, Hugen P, Droste J, Huitema A Abstract: TDM of NFV and IDV in treatment-naïve patients improves treatment outcome and should become standard of care. |
| 31. | EFFECTS OF PROLONGED DISCONTINUATION OF SUCCESSFUL ANTIRETROVIRAL THERAPY Tebas P, Henry K, Mondy K, Deeks S, Valdez H, Cohen C, Powderly W Abstract: CD4 cells counts decline progressively after discontinuing successful antiretroviral therapy. Most of the patients remained asymptomatic (if CD4 >200). Eleven subjects that restarted therapy reached undetectability again, suggesting that virologic resistance does not appear. Strategies that administer therapy intermittently, with prolong periods of treatment interruption deserve further evaluation. |
| 32. | CLINICAL AND IMMUNOLOGIC OUTCOMES ACCORDING TO DIFFERENT LEVELS OF VIROLOGIC SUPPRESSION (VS) AFTER UNDETECTABILITY ON HAART Abgrall S, Duval X, Joly V, Descamps D, Matheron S, Costagliola D Abstract: To evaluate factors associated with a durable virologic suppression (DVS) on HAART or different levels of viral rebound (VR) and to estimate the subsequent clinical and immunologic outcomes. |
| 33. | DURATION OF ANTIRETROVIRAL ADHERENCE PREDICTS BIOLOGIC OUTCOMES IN CLINICAL TRIALS Friedland GH, Mannheimer S, Matts J, Child C, Telzak E, Chesney M Abstract: Both the level and duration of self reported adh predicts therapeutic outcome. The maintenance of consistent high levels of adh is critical and a significant determinant of virologic outcome. Long-term interventions to maintain high levels of adh are needed. |
| Session 6, Oral: Prevention and Access to ARV in Resource - Limited Settings Monday, July 9th |
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| 34. | THE CASE FOR ANTIRETROVIRALS Lange, J. Abstract: Not submitted. |
| 35. | THE ABSTRACTS FOR THE INTRODUCTION OF ARV IN RESOURCES POOR SETTINGS Covadia, H. Abstract: Not submitted. |
| 36. | A ROLE OF THE PRIVATE SECTOR Tsetsele Fantan Abstract: The Government of Botswana and De Beers Centenary AG own Debswana Diamond Company in equal shares. The Company mine diamonds at three locations in Botswana namely Orapa, Letlhakane and Jwaneng. In addition the Botswana Diamond Valuing Company which sorts and values diamonds, the Teemane Manufacturing Company which cuts and polishes diamonds and Morupule Colliery are wholly owned subsidiaries of Debswana. The Company head office is in Gaborone.The Company contributes 33% of GDP, up to 65% of government revenue and over 80% of foreign exchange from diamonds. It is one of the major employers and provides a substantial portion of the technical training in the country. The Company operates in a high HIV prevalence country and region. At the end of 1999, the adult prevalence rate was estimated at 35.8% and in 2000 it was at 38.5%. |
| 37. | AFRICAN COMPREHENSIVE HIV/AIDS PARTNERSHIP (ACHAP) de Korte, Donald F Abstract: All activities are being conducted in close collaboration with the National Coordinating AIDS Agency, Ministry of Health in Botswana and other key stakeholders. |
37b. | WHAT CAN THE PUBLIC SECTOR DO Anabwani, G. Abstract: Not submitted |
| 38. | THE CURRENT STATUS OF ACCESS TO ANTIRETROVIRAL THERAPY IN THE WORLD Vitoria, M Abstract: The direct and indirect causes for this dramatic scenario are obvious, but the short and long term solutions are apparently difficult to implement, involving a strong and organized effort by the international community associated with political commitment by local governments, more effective and flexible negotiation with pharmaceutics industries. In this context, the participation of civil society in the whole process will be crucial. |
| Session 7, Oral: Liver Diseases and HIV Monday, July 9th |
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| 40. | HIV AND HEPATITIS: A STORY OF SCRAMBLED LETTERS Francesca J. Torriani Abstract: Meanwhile, more studies should focus on the mechanisms involved with sexual transmission, on HCV virus and host factors leading to the persistence of this infection, on plasma and hepatic viral dynamics in acute infection and during treatment. Finally, because the available therapies are scarce at this time, new drug combinations should be evaluated. |
| 41. | MECHANISMS OF DRUG INDUCED HEPATOTOXICITY Marion Peters Abstract: Drug induced hepatotoxicity in HIV subjects has become of increasing importance in the era of HAART, especially with the high incidence of viral hepatitis and non alcoholic steatohepatitis in these subjects. |
| 42. | PEGYLATED INTERFERON PLUS RIBAVIRIN FOR THE TREATMENT OF CHRONIC HEPATITIS C IN HIV-INFECTED PATIENTS Soriano, V; García-Samaniego, J; Pérez-Olmeda, M; Barreiro, P; Núnez, M; Rodríguez-Rosado, R; Jiménez-Nácher, I Abstract: The combination of Peg-IFN and RBV is relatively well-tolerated and provides a high rate of virological and biochemical response in the short-term in HIV+ subjects with CHC. |
| 43. | INCIDENCE OF HEPATOTOXICITY AND MORTALITY IN 21 ADULT ANTIRETROVIRAL TREATMENT TRIALS Reisler, R; Liou, S; Servoss, J; Robbins, G; Theodore, D; Murphy, R; Chung, R Abstract: In a large U.S. HIV cohort (1) there is a high rate of severe ART hepatotoxicity irrespective of class. (2) in all groups except PI-containing triple regimens, severe hepatotoxicity led to frequent permanent treatment discontinuation. (3) of reported deaths, there was a significant hepatic-associated mortality. (4) among NNRTIs, there was a high rate of hepatotoxicity, particularly with NVP and EFV, with high rates of discontinuation; mortality was infrequent. |
| 44. | ANALYSES OF FOUR KEY CLINICAL TRIALS TO ASSESS THE RISK OF HEPATOTOXICITY WITH NEVIRAPINE: CORRELATION WITH CD4+ LEVELS, HEPATITIS B & C SEROPOSITIVITY, AND BASELINE LIVER FUNCTIONS TESTS Dieterich, D; Stern, J; Robinson, P; Hall, D; Carlier, H Abstract: Population based cohort studies have suggested the incidence of hepatic events in NVP treated patients is low. Observed rates in clinical trials appear to depend on several risk factors: baseline CD4+ >= 350 cells/mm³, baseline ALT/AST or co-infection with Hep B or C. |
| 45. | HEPATIC AND CUTANEOUS TOXICITY ATTRIBUTED TO NEVIRAPINE (NVP) Bennett, C; Johnson, S; Lynch, P; Lloyd, K; Murphy, R Abstract: NVP should be targeted to persons with CD4s < 200 cells/mm³ and accompanied by liver function monitoring during the first three months of treatment. |
| Session 8, Oral: State of the Art in Envelope & Receptor Interactions Monday, July 9th |
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| 46. | FUSION INHIBITORS IN CLINICAL DEVELOPMENT Eron, J. Associate Professor of Medicine Abstract: Combination antiretroviral therapy has had a profound impact on the clinical management of HIV-1 infection. However, despite the availability of 15 or more anti-HIV agents, toxicity and drug resistance severely limit the long-term control of viral replication in many HIV-1 infected individuals. This presentation focuses on new classes of antiretroviral agents directed at preventing entry of HIV-1 into susceptible cells by inhibiting fusion of the virus with the host cell membrane. |
| 47. | COMBINATION THERAPY WITH ATTACHMENT/ENTRY INHIBITORS Cecile Tremblay Abstract: A better understanding of the attachment and fusion process will help us define how to use agents targeting different steps of the entry process, either combined with each other or with antiretrovirals from other classes. |
| 48. | DC-SIGN ON DENDRITIC CELLS, NOVEL HIV RECEPTOR, RELATED MOLECULES Yvette van Kooyk Abstract: DC-SIGN captures HIV-1 through a mannose dependent interaction with the envelope glycoprotein gp120. Deglycosylation of gp120 results in a complete loss of its bindings activity to DC-SIGN. DC-SIGN does not function as a receptor for viral entry into DC, but instead promotes efficient infection in trans of cells that express CD4 and chemokine receptors. Mutational analysis demonstrate unique but distinct residues in DC-SIGN that regulate capture of HIV and binding of ICAM molecules. Closely located to the gene of DC-SIGN a highly homologous receptor which we named L-SIGN was identified. L-SIGN functions similar to DC-SIGN a HIV-gp120 binding receptor but its tissue is completely distinct from that of DC-SIGN. These studies suggest that the interaction between DC-SIGN and L-SIGN with gp120 may be an important target for therapeutic intervention and vaccine development. |
| 49. | HIV-1 CORECEPTORS AND THE DETERMINANTS OF PATHOGENESIS IN LYMPHOID TISSUES. Mark A. Goldsmith Abstract: The determinants of HIV-induced pathogenesis in lymphoid tissue environments are only partially understood. Specifially, the roles played by the cellular states of activation, replication and differentiation in governing susceptibility to infection and/or depletion by HIV-1 are not fully delineated. In order to define further the molecular determinants of infection and pathogenesis, we have exploited ex vivo human lymphoid histocultures that recapitulate certain virus/host interactions that are integral to disease development in vivo. |
| Session 9, Invited Lectures 1-2 Monday, July 9th |
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| IL-1. | MAKING SENSE OF PRIMATE LENTIVIRAL ACCESSORY GENE FUCTIONS Stevenson, M. Abstract: The genomes of primate immunodeficiency viruses contain several novel open reading frames which encode the so-called accessory proteins. |
| IL-2. | NEW ANTIRETROVIRAL AGENTS IN LATE CLINICAL DEVELOPMENT Murphy, Robert Abstract: Of specific interest, there appears to be no effect on serum lipid levels, a potentially significant advantage over other protease and non-nucleoside reverse transcriptase inhibitors. The only problem to date has been elevations in indirect bilirubin of unknown clinical consequence. The new agents in development are likely to provide further options and significant benefit for patients initiating therapy and for those requiring therapy following treatment failure. |
| Session 10, Oral: Invited Lectures 3-4 Monday, July 9th |
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| IL-3. | MODELING T CELL DYNAMICS DURING HIV INFECTION Alan S. Perelson Abstract: Analyzing these results with a newly developed mathematical model indicates that both CD4+ and CD8+ lymphocyte turnover rates are elevated several-fold in HIV-1 infection, and these rates begin to normalize within a few months of effective antiretroviral therapy. This implies that the major immunologic consequence of successful treatment is to reduce lymphocyte destruction and turnover, not to enhance cellular production or re-distribution. |
| IL-4. | COST-EFFECTIVENESS OF HAART Kenneth A. Freedberg Abstract: These methods can also be used to understand the value of HIV prevention efforts. HIV control in low-income countries will likely depend on a balance of prevention and treatment interventions. Formal cost-effectiveness analysis provides a valuable mechanism for generating the kind of information that clinicians and policy makers need to achieve such a balance. |
| Session 11, Oral: Update on Resistance Monday, July 9th |
50-52. | "REVIEW AND CLINICAL IMPLICATIONS OF THE NEW DEVELOPMENTS IN DRUG RESISTANCE AND NOVEL STRATEGIES IN HIV THERAPY" Boucher, C.; Larder, B.; Mellors, J.; Richman, D. Abstract: Not submitted. |
| Session 12, Oral: Update on Pharmacological Issues Monday, July 9th |
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| 53. | PHARMACOGENOMICS David J Back Abstract: In relation to HIV and drug therapy areas of particular interest are polymorphism in drug metabolising enzymes and transport molecules. The potential consequence of an individual having either a poor metaboliser genotype or an ultrarapid metaboliser genotype will be reflected in altered pharmacokinetic profiles and consequently response. Some of the polymorphic enzymes are CYP2C9, CYP2C19, CYP2D6, NAT, UDPGT (?). There is also recent data showing that variability in expression of P-glycoprotein is determined by a polymorphism in exon 26 and that individuals with the variant genotype have altered kinetics of several drugs. Currently studies in HIV positive patients are focussing on relating plasma and intracellular concentrations of antiretrovirals to transporter expression, function and genotype. Another area of considerable interest is the possible overepresentation of certain alleles in patients with lipodystrophy. We are well and truly in the post-genomic era and have to face the exciting challenges head on in order to ensure that patients receive maximal benefit from existing and new drugs. |
| 54. | THERAPEUTIC DRUG MONITORING: A MUST FOR CLINICAL PRACTICE? David Burger Abstract: Many laboratories are now introducing TDM. It is important to recognize that external quality control is essential before TDM is used in patient care. For the protease inhibitors and the non-nucleoside reverse transcriptase inhibitors relationships between plasma levels and effect have been demonstrated. Target concentrations can be defined, but it is important to realize that in treatment-experienced patients also the sensitivity of the virus to the drug should be determined. There is a wide range of possible interventions (dose modifications, addition of low-dose ritonavir, etc.) to improve the pharmacokinetics, but few studies have evaluated these strategies. Measuring drug levels is meaningless if physicians do not follow the advices, so the introduction of TDM should be accompanied by educational programs. Finally, two randomized controlled trials have been presented recently. The French Pharmadapt study included treatment-experienced patients and could not demonstrate any benefit of TDM. The Dutch Athena study has shown that TDM of nelfinavir and indinavir in treatment-naïve patients improves the outcome after one year of follow-up. A couple of other TDM studies are now ongoing and will show us how to use TDM in clinical practice. |
| 55. | DRUG INTERACTIONS IN HIV MEDICINE: HOW MUCH DO THEY MATTER? Stephen C. Piscitelli Abstract: The study and management of drug interactions in HIV-infected patients has undergone dramatic changes within the past 5 years. Originally considered a problem that needed to be avoided, the use of certain drug interactions has become standard of care to increase adherence, lower pill burden, improve convenience, and even lower costs. Dual protease inhibitors have become a classic example of how to use pharmacokinetic interactions to improve drug therapy. However, a number of issues remain including which doses/regimens are most effective, management of toxicity, and wide inter-patient variability. |
| Session 13, Oral: Antiretroviral Therapy Tuesday, July 10th |
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| 56. | STI VS. CONTINUOUS HAART DURING CHRONIC HIV INFECTION Lori F, Foli A, Tomasoni L, Maggiolo F, Hurwitz S, Lisziewicz J, Maserati R Abstract: Encouraging (VL decrease and CD4 increase similar to continuous therapy, or improved) and tempering (transient CD4 loss and VL rebound without set-point reduction) results must be weighed to assess whether STI is a valuable alternative for long-term control of HIV. |
| 57. | EVALUATION OF A TRIPLE COMBINATION REGIMEN CONTAINING ENTERIC COATED DIDANOSINE ADMINISTERED ONCE-DAILY Badaro R, Gathe J, Grimwood A, McLaren C, Klesczewski K Abstract: VIDEX EC capsules dosed QD provide antiviral activity in a triple regimen similar to a reference triple regimen in treatment-naïve, HIV-infected subjects. |
| 58. | A RANDOMIZED STUDY OF TREATMENT SIMPLIFICATION WITH NEVIRAPINE (NVP) OR EFAVIRENZ (EFV) IN PATIENTS RESPONDING TO A PROTEASE INHIBITOR(PI) BASED COMBINATION. Patterson P, Krolewiecki A, Ochoa C, Pryluka D, Perez H, Zala C, Cahn P Abstract: These preliminary data suggest that switching from a PI-containing HAART to either NVP or EFV allow a continued control of viral replication. However, in this study treatment-limiting toxicity was higher in the NVP arm. |
| 59. | HIV-NAT 001.3: The safety, efficacy and pharmacokinetics (PK) of 1,600 mg saquinavir (soft-gelatin capsules; SQV-SGC) plus low dose ritonavir (RTV, 100 mg) in a once-daily (qd) dosing regimen in HIV-1-infected Thai patients Cardiello P, Van Heeswijk R, Monhaphol T, Ubolyam S, Cooper D, Lange J, Phanuphak P Abstract: Both our clinical and PK results support the use of SQV-SGC/RTV 1,600/100 mg qd as a convenient regimen to maintain suppression of viral replication in patients with a pVL < 50 copies/mL, in combination with two NRTIs. |
| 60. | CONTINUED INDINAVIR (800 mg TID) VERSUS SWITCHING TO INDINAVIR+RITONAVIR (800/100 mg BID) IN HIV PATIENTS HAVING ACHIEVED VIRAL LOAD SUPPRESSION. A RANDOMIZED STUDY:THE BID EFFICACY AND SAFETY TRIAL Cahn P, Casiró A, Puentes T, David D, Richter C, Stek M, Gatell J Abstract: BID administration of IDV 800 mg with RTV 100 mg is generally well tolerated and maintains viral suppression in stable HIV-infected patients in comparison with the standard TID regimen. Final data at 12 months will be presented. |
| 61. | GREATER SUPPRESSION OF CD8 ACTIVATION WITH 4 VS 3 DRUGS IN EARLY STAGES OF PRIMARY HIV INFECTION (PHI) DESPITE SIMILAR PLASMA VIROLOGICAL DECAY RATES. Smith D, Zaunders J, Kauffman G, Cunningham P, Grey P, Goh L, Cooper D Abstract: Although viral load decay rates did not differ with the use of more ARV agents in very early PHI disease in this non-randomised study, immunological markers of T-cell activation were significanlty reduced, suggesting greater suppression of HIV replication, below the currently detectable levels in plasma |
| 62. | DIFFERENCES IN VIROLOGIC SUPPRESSION AMONG MEN AND WOMEN ENROLLED IN A POPULATION-BASED ANTIRETROVIRAL DRUG TREATMENT PROGRAM O'connell J, Braitstein P, Hogg R, Yip B, O'Shaughnessy M, Montaner J, Burdge D Abstract: To characterize the determinants of plasma HIV-RNA suppression to below 500 copies/mL in women and men in British Columbia, and to explore possible gender differences in plasma viral load suppression after antiretroviral therapy. |
| 63. | ABACAVIR/COMBIVIR (ABC/COM) IS COMPARABLE TO INDINAVIR/COMBIVIR IN HIV-1 INFECTED ANTIRETROVIRAL THERAPY NAÏVE ADULTS: PRELIMINARY RESULTS OF A 48-WEEK OPEN LABEL STUDY (CNA3014) Vibhagool A, Cahn P, Schechter M, Soto-Ramirez L, Montroni M, Smaill F, Thomas N Abstract: To compare efficacy, safety and adherence of ABC (300mg bid) plus COM (150mg lamivudine and 300mg zidovudine bid) vs. IDV (800mg tid) plus COM. |
| Session 14, Oral: Opportunistic Diseases Tuesday, July 10th |
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| 64. | OPPORTUNISTIC INFECTIONS IN THE ERA OF HAART William G. Powderly Abstract: The incidence of AIDS-associated opportunistic infections (OIs) in the developed world, and, with it, the death rate from AIDS, has declined dramatically, with decreases in the major indicator OIs, such as PCP, CMV retinitis, and MAC of up to 85% compared with rates in the early 1990s. The changing rate of OIs is clearly linked to more potent antiretroviral therapy. |
| 65. | TB AND HIV STILL TOGETHER Gatell, J. Abstract: Not submitted. |
| 66. | ANTIRETROVIRAL THERAPY REDUCES THE RISK OF TUBERCULOSIS IN A HIGH PREVALENCE SETTING Wilson D, Badri M, Stuve K, Maartens G, Wood R Abstract: To assess the impact of antiretroviral regimens on the incidence of tuberculosis (TB) in HIV-infected patients in a high TB prevalence setting. Materials: Patients presenting between 1992 and 1997 to one HIV Unit in Cape Town, South Africa (background incidence of TB 680 / 100 000). |
| 67. | HIV-INFECTED INTRAVENOUS DRUG USERS ARE AT HIGH RISK OF ANAL SQUAMOUS INTRAEPITHELIAL LESIONS RELATED TO HPV INFECTION Piketty C, Darragh T, Da Costa M, Bruneval P, Heard I, Kazatchkine M, Palefsky J Abstract: A high prevalence of anal squamous intraepithelial lesions (SIL) and HPV infection have been observed in HIV-infected homosexual males. To date, the prevalence of anal SIL and HPV infection have not been evaluated in HIV-infected intravenous drug users (IVDU) in the absence of receptive anal intercourse. |
| 68. | ORAL SHEDDING AND PROPAGATION OF HHV-8 IN PHARYNGEAL LYMPHOID TISSUES: POTENTIAL COFACTOR ROLE OF HIV
Brodie S, Johnson A, Vieira J, Koelle D, Wald A, Corey L Abstract: Kaposi’s sarcoma (KS) is a predominant opportunistic disease associated with HIV, both in the USA and in the developing world. While HHV-8 appears to be sexually transmitted among men who have sex with men (MSM), acquisition during early childhood is also well documented. Even among MSM, the mode of transmission is unclear. We have previously shown HHV-8 to be present in saliva in high titer. Here, we focus attention on the biology of oral infection, particularly the site(s) of virus replication in the oropharynx and factors that determine frequency and concentrations of HHV-8 in saliva. |
| 69. | NON-HODGKIN LYMPHOMA (NHL) AMONG HIV-INFECTED PATIENTS IN THE ERA OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART) Kirk O, Mocroft A, Barton S, Pedersen C, Skinhøj P, Miller V, Lundgren J Abstract: To analyse the influence of HAART on the risk of NHL among HIV-infected patients. |
| Session 15, Oral: Co-receptors as Therapeutic Targets Tuesday, July 10th |
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| 70. | SECOND GENERATION CCR5 ANTAGONIST THAT INHIBITS HIV-1 ENTRY Bahige M. Baroudy, Ph.D. Abstract: We previously described the development of SCH 351125 (SCH-C), a small molecule CCR5 antagonist, as a potent inhibitor of HIV-1 entry. This compound inhibited the replication of genotypically diverse HIV-1 isolates in human peripheral blood mononuclear cells. |
| 71. | QST-DIH -RANTES: A NOVEL CCR5 LIGAND WITH POTENT ANTI-HIV ACTIVITY Picchio G, Pastore C, Galimi F, Chaloin O, Hartley O, Offord R, Mosier D Abstract: Prevention of HIV-1 entry into target cells by amino-terminal modified CCR5 ligands is an attractive potential therapeutic approach. In this study, we report on CCR5 internalization and anti-HIV-1 activity of QST-DIH-RANTES, a new member of this family of compounds. |
| 72. | PHENOTYPIC AND ANTIGENIC PROPERTIES ASSOCIATED WITH PATHOGENIC R5-TROPIC SHIVSF162P3 Hsu M, Yang D, Cheng-Mayer C Abstract: To characterize the properties of Env associated with increased pathogenicity of R5-specific SHIVSF162P3. |
| 73. | EXPRESSION OF CXCR4 AND SDF-1 IN PERIPHERAL T-CELLS AND LYMPH NODES. Bermejo M, Martin-Serrano J, De Pablos J, Gamallo C, Arenzana F, Alcami J Abstract: To analyze the expression and regulation of CXCR4 in resting and activated peripheral blood lymphocytes and the distribution of SDF-1 in lymph nodes. |
| 74. | POTENT ANTI-HIV CHEMOKINE ANALOGUES PRODUCED THROUGH A PHAGE DISPLAY SELECTION STRATEGY. Gorochov G, Hartley O, Oorgham K, Pancino G, Debre P, Offord R Abstract: the chemokine receptors CCR5 and CXCR4 are promising targets for HIV therapy. We have used a phage display approach to isolate mutant forms of RANTES with antiviral activity considerably in excess of the native sequence. |
| 75. | SENSITIVITY OF HIV-1 TO FUSION INHIBITORS IS MODULATED BY CORECEPTOR SPECIFICITY AND INVOLVES DISTINCT REGIONS OF GP41 Derdeyn C, Decker J, Sfakiands J, D´Brien W, Ratner L, Shaw G, Hunter E Abstract: T-20 is a synthetic peptide that corresponds to 36 amino acids within the C-terminal heptad repeat region (HR2) of HIV-1 gp41. T-20 has been shown to potently inhibit viral replication of HIV-1 both in vitro and in vivo and is currently being evaluated in a phase III clinical trial. |
| 76. | MECHANISMS FOR STIMULATION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 REPLICATION BY AOP-RANTES Marozsan A, Torre V, Ball S, Cross J, Templeton D, Quinones-Mateu M, Arts E Abstract Aminooxypentane (AOP)-RANTES, an analog of the chemokine RANTES(Regulated upon Activation Normal T-cell Expressed and Secreted), is a potent inhibitor of CCR5-tropic (R5) viral replication. |
| Session 16, Oral: T-Cell Immunity and T-Cell Turnover Tuesday, July 10th |
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| 77. | THE CD4 T CELL RECEPTOR REPERTOIRE DURING PATHOGENESIS AND IMMUNE RECONSTITUTION Sékaly, Rafick-Pierre; Yassine-Diab, Bader; Younes, Souheil; Breton, Gaëlle; Poulin, Jean-François and Cheynier, Rémi. Abstract: Our results clearly indicate that decline in CD4+ T cells can be caused by two independent mechanisms; first a defect in the production of those cells is clearly apparent; second, those cells which are produced and get activated by HIV are quickly eliminated by the virus through direct or indirect cythopathic mechanisms. |
| 78. | LONGITUDINAL INTERPLAY OF CD8+ T-CELL RESPONSES AND THE HIV-1 DERIVED P17 EPITOPE THEY RECOGNIZE DURING CHRONIC HIV-1 INFECTION Jamieson B, Yang O, Hultin L, Altman J, Korber B, Giorgi J, Wolinsky S Abstract: CTL are important for the control of HIV-1 infection, yet they usually fail to adequately suppress the virus. |
| 79. | PARTIAL RESTAURATION ON HIV-SPECIFIC CD4 T CELL RESPONSES WITH DENDRITIC CELLS. Grassi F, Carcelain G, Bonduelle O, Alatrakchi N, Valantin M, Katlama C, Autran B Abstract: addition of DC and IL-12 similarly enhances the HIV-specific memory CD4 Th responses in slow progressors but not in progressors even when treated, suggesting that defects in APCs might play a role in, but cannot compensate, the quantitative defects of HIV-specific CD4 Th1 cells. |
| 80. | IMPACT OF IL-7 ON ADULT HUMAN THYMIC SUBSETS Jamieson B, Zack J, Scripture-Adams D Abstract: Our previous data show that the adult thymus generates new thymocytes similar to fetal thymocytes in their subset distributions, response to co-stimulatory signals, and diversity of TCR-Vb repertoires, suggesting that newly formed T-cells in adults may functionally respond to a broad array of antigens. |
| 81. | ANALYSIS OF T-LYMPHOCYTE TURNOVER RATES USING NOVEL MODELS FOR THE STUDY OF DEUTERATED GLUCOSE Ribeiro R, Mohri H, Ho D, Perelson A Abstract: The elucidation of T-cell turnover dynamics is crucial for an understanding of HIV pathogenesis. New methods to measure that turnover have been developed, including the use of deuterated glucose. |
| 82. | "LONG-TERM MEMORY" AND "EFFECTOR MEMORY" CD4 PHENOTYPE BASED ON EXPRESSION OF CD62L AND CD45-ISOFORMS PREDICTS PATTERNS OF CELL DIVISION AND DIFFERENTIATION Hengel R, Pavlick M, Lempicki R, Metcalf J, Lane H Abstract: Expression of the ligand (CD62L) that facilitates lymph-node entry through high endothelial venule can be used to characterize subsets of CD4 and CD8 T cells. |
| 83. | CTLA-4 UPREGULATION DURING HIV INFECTION: ASSOCIATION WITH ANERGY AND POSSIBLE TARGET FOR THERAPEUTIC INTERVENTION. Borkow G, Leng Q, Magen E, Kalinkovich A, Bentwich Z Abstract: The cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), a negative regulator of T-cell proliferation, plays an important role in peripheral CD4+/CD8+ T-cell homeostasis and in induction of anergy. |
| Session 17, Oral: Animal Models for HIV Pathogenesis Tuesday, July 10th |
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| 84. | SW VIRAL SCAPE AND PATHOGENESIS Franchini, G. Abstract: Not submitted |
| 85. | A NOVEL HIV-1 TRANSGENIC RAT MODEL OF HIV-NEPHROPATHY (HIVAN) Ray P, Liu X, Reid W, Haynes N, Davis H, Bryant J Abstract: HIVAN is associated with proteinuria, focal or segmental glomerulosclerosis, and tubulointerstitial lesions leading to end stage renal disease. |
| 86. | INFLUENCE OF ITAM MOTIF OF CHIMERIC SIMIAN/HUMAN IMMUNODEFICENCY VIRUS SHIVSBG-NEFYE ON VIRULENCE IN CHINESE RHESUS MACAQUES Lafont B, Gloeckler L, Beyer C, Einius S, Gut J, Aubertin A Abstract: The SHIVsbg, expressing the Vpu, Tat, Rev and Env proteins of HIV1 Lai was shown to be pathogenic for rhesus macaques and cynomolgus monkeys. |
| 87. | RELATIVE DYNAMICS OF SIV REPLICATION AND IMMUNE RECOGNITION: DELAYED INFILTRATION OF ANTI-SIV CTLS ALLOWS VIRAL ESCAPE Blancou P Abstract: Anti-SIV CTLs are thus infiltrating the DTH sites at least 12 hours after the initiation of local SIV replication allowing viral dissemination within the immune reaction site. This finding suggests that, even in the presence of a huge local CTL response infected antigen-specific CD4 T cells can escape from the site of immune activation to re-seed the pool of resting SIV-infected peripheral T cells |
| 88. | EARLY AND PERSISTENT HEMATOPOIESIS FAILURE IN SHIV INFECTED MACAQUES DESPITE EFFICIENT HAART Thiebot H, Vaslin B, Louache F, De Revel T, Vainchenker W, Dormont D, Le Grand R Abstract: To evaluate, in the model of macaques infected with a pathogenic simian/human chimeric virus (SHIV), the impact infection on bone marrow primitives or differentiated hematopoietic progenitor cells. |
| 89. | CONSEQUENCES ON IMMUNE FUNCTIONS OF EARLY POST-EXPOSURE PROPHYLAXIS WITH HAART IN THE MODEL OF SHIV INFECTED MACAQUES. Le Grand R, Benhlassan K, Bossuet C, Thiébot H, Bosquet N, Vaslin B, Dormont D Abstract: Starting HAART within few hours after IV exposure, as recommended for treatment of accidental exposure to HIV, did not prevent from infection. |
| 90. | ROLE OF CD154 SIGNALLING DURING INFECTION OF MACAQUES WITH SIV Giavedoni L, Hodara V, Velasquillo M, Parodi L Abstract: To analyze mechanisms of cellular immune responses to retroviral infections. |
| Session 18, Oral: Toxcities of ART Tuesday, July 10th |
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| 91. | BONE DISEASE IN HIV Pablo Tebas Abstract: People living with HIV have significant alterations in bone metabolism regardless of whether or not they are receiving potent antiretroviral therapy. The underlying mechanisms to account for these observations remain unknown, although studies are underway to examine the relationship between the bone abnormalities and other complications associated with HIV and antiretroviral therapy. HIV-infected patients with osteopenia or oseoporosis should be treated similarly to seronegative patients with appropriate use of nutritional supplements (Calcium and Vitamin D) and exercise. Hormone replacement and antiresorptive therapies might be also indicated. |
| 92. | SHORT-TERM IMMUNO-SUPPRESSIVE THERAPY WITH PREDNISOLONE IN HIV-1-INFECTED PATIENTS RECEIVING ABACAVIR WITH OR WITHOUT NEVIRAPINE Wood R, Wit F, Horban A, Beniowski M, Schmidt R, De Vries C Abstract: It has been suggested that use of prednisolone (pred) might prevent the occurrence of hypersensitivity reactions (HSR) and/or rash which are common causes of abacavir (ABC) and nevirapine (NVP) discontinuations. |
| 93. | EFFECT OF NUCLEOSIDE (NRTI) INTENSIFICATION ON PREVALENCE OF MORPHOLOGIC ABNORMALITIES (MOAS) AT YEAR 4 OF RITONAVIR (RTV) PLUS SAQUINAVIR (SQV) THERAPY IN AN HIV-INFECTED COHORT Cohen C, Ryan J, Jiang P, Cameron D, Mellors J, Kakuda T, Japour A Abstract: An ongoing RTV/SQV study with and without NRTI intensification allows partitioning the effect of NRTI therapy from PI therapy on the prevalence and risk factors of MoAs. |
| 94. | COMBINED ANTIRETROVIRAL THERAPY CAUSES CARDIOMYOPATHY Lewis W, Haase C, Raidel S, Russ R, Sutliff R, Samarel A Abstract: Highly active antiretroviral therapy (HAART) for AIDS is implicated in cardiomyopathy (CM) and reported to cause elevated plasma lactate (LA) through mechanisms of mitochondrial dysfunction. |
| 95. | MITOCHONDRIAL DNA DEPLETION IN HIV+ PATIENTS WITH SYMPTOMATIC NUCLEOSIDE RELATED MITOCHONDRIAL TOXICITY. Cote H, Brumme Z, Wynhoven B, Harris M, Craib K, Harrigan P, O'Shaughnessy M Abstract: Mitochondrial toxicity (MT)-related adverse effects include acute lactic acidosis as well as chronic hyperlactatemia that may or may not be symptomatic. |
| 96. | A RANDOMISED TRIAL OF THYMIDINE ANALOGUE WITHDRAWAL IN LIPOATROPHIC HIV PATIENTS, VIROLOGICALLY CONTROLLED ON PROTEASE SPARING THERAPY - THE PIILR EXTENSION STUDY. Smith D, Carr A, Law M, Hudson J, Hoy J, Cooper D Abstract: Nucleoside analogue induced mitochondrial toxicity has been implicated in the loss of subcutaneous fat (lipoatrophy) in patients on HAART therapy. |
| Session 19, Oral: Preventive HIV Vaccines: Clinical Trials Tuesday, July 10th |
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| 97. | WHAT HAVE WE LEARNT FROM CLINICAL TRIALS OF HIV VACCINES? J. Esparza Abstract: In the meantime, two different gp120 candidate vaccines are being tested in phase III trials in the United States (gp120BB) and Thailand (gp120BE), to obtain definitive information on their potential efficacy in protecting against HIV infection or disease. At the same time novel HIV candidate vaccine are being investigated and developed, including DNA constructs, new vectors (VEE, MVA, Adenovirus) and adjuvants, different-prime boost regimes, and candidates based on primary (R5) isolates of HIV. |
| 98. | DESIGNING AND PREPARING FOR HIV VACCINE EFFICACY TRIALS Susan Buchbinder Abstract: Trials can be designed to have substantial power to detect such immune correlates, even with low levels of overall efficacy (e.g., in the order of 10-20% overall efficacy). Such clinical correlates will provide critical information for assessing the relevance of animal models, and for further design or refinement of novel or existing vaccine strategies. Trials can also be designed to evaluate indirect evidence of protection, by comparing vaccine genotypic and phenotypic characteristics of infected vaccine and placebo recipients. However, such trial designs will require the informed involvement of thousands of volunteers. Critical components in this effort are the inclusion of vaccine trial sites with the political support, investigator expertise, and community involvement to ensure that such trials minimize potential harm to study participants while maximizing scientific insights that such trials can provide. |
| 99. | THAILAND'S EXPERIENCE WITH THE FIRST INTERNATIONAL PHASE III EFFICACY TRIAL OF AN HIV VACCINE (AIDSVAXR) Sricharoen Migasena, Kachit Choopanya, William Heyward Abstract: Varied recruitment efforts and an effective informed consent process led to the successful enrollment of 2545 IDUs by August 2000. Thus far, immunization compliance and follow-up have been excellent, data management and GCP conducted at international standards, and social harms minimal. Immunizations have been well tolerated with no vaccine-related serious adverse events reported. Data collected in this trial will meet international standards and can be used for licensing purposes. The trial is expected to conclude in late 2002. |
| 100. | WHAT CAN WE LEARN FROM EPIDEMIOLOGICAL AND NATURAL HISTORY STUDIES? Francis A. Plummer Abstract: These natural experiments indicate that adaptive immunity may be involved in protecting some individuals from HIV and that MHC alleles and immunoregulatory genes may be involved in the genesis of protective adaptive immunity. Furthermore they provide important clues as to what might be required for successful HIV vaccines. |
| 101. | Abstract: Not submitted. |
| Session 20, Oral: Therapies Directly Targeting the Immune System Tuesday, July 10th |
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| 102. | ILSTIM (ANRS 082) - INTERLEUKIN 2 (IL2) ACCELERATES CD4 CELLS RECONSTITUTION IN PATIENTS WITH CD4 <200/MM3 DESPITE EFFECTIVE HAART. Tubiana R, Carcelain G, De Sa M, Autran B, Duviver C, Costagliola D, Katlama C Abstract: To evaluate the capacity of IL2 to restore immunity in patients with CD4<200/mm³ despite HAART. |
| 103. | INTERMITTENT IL-2 ADMINISTRATION IN HIV INFECTED PATIENTS LEADS TO A DECREASE IN CD4+ T CELL TURNOVER RATES Sereti I, Martinez-Wilson H, Metcalf J, Kovacs J, Lane H Abstract: Intermittent administration of IL-2 in HIV infected patients leads to a sustained expansion of the CD4+ but not CD8+ T cell pool although substantial increases in proliferation are seen in CD8+ as well as CD4+ T cells during an IL-2 cycle. |
| 104. | ADJUVANT SCIL2 INCREASES THYMIC PRODUCTION IN PATIENTS WITH ADVANCED HIV INFECTION UNDER ANTIRETROVIRAL THERAPY Korthals Altes H, Saint-Mezard P, Tubiana R, De Boer R, Katlama C, Autran B, Carcelain G Abstract: Interleukin-2 (IL-2) increases CD4+ T cell numbers by enhancing mature T cell proliferation but its effect on naïve T cell homeostasis and thymic function is unknown. |
| 105. | QUALITY OF LIFE IN A RANDOMIZED CONTROLLED TRIAL OF HIGHLY ACTIVE ANTI-RETROVIRAL THERAPY WITH INTERMITTENT IL-2 BY IV OR SC ROUTES IN PATIENTS WITH CD4 50-350 CELLS/MM3 (ACTG 328) Wu, A; Martin, B; Gelman, R; Mitsuyasu, R Abstract: In this large prospective randomized study of IL-2 in advanced HIV, significant increases in CD4+ counts were seen and QOL was not significantly diminished after 40 weeks of intermittent SC IL-2. A significant QOL benefit was seen in the SC IL-2 group compared to IV IL-2 and HAART alone groups. |
| 106. | SAFETY AND ACTIVITY OF RECOMBINANT HUMAN INTERLEUKIN-12 (RHIL-12) IN HIV+ PATIENTS Pollard R, Jacobson M, Landay A, Spritzler J, Fox L, Schock B, Chan E Abstract: To evaluate the safety and activity of rhIL-12, a cytokine that stimulates T and NK cells to generate a TH1 type immune response. |
| 107. | HYDROXYUREA THERAPY SPARES THE NAÏVE T CELL COMPARTMENT IN PATIENTS TREATED WITH ANTIRETROVIRAL DRUGS: THE 3D STUDY Ogorman M, Alatrakchi N, Belsey E, Landay A, Katlama C, Murphy R, Autran B Abstract: The increase in proportion and number of naïve CD4 T cells without a sig.increase in the absolute CD4 count indicates a relative decrease in the memory CD4 T cell compartment in HU treated patients. |
| 108. | EFFECT OF IL-2 ON RESPONSES TO HIV AND TETANUS IMMUNIZATION: RESULTS OF ACTG 5046S Valdez H, Mitsuyasu R, Sahner D, Moss R, Landay A, Sevin A, Lederman M Abstract: strong lymphocyte proliferative responses (LPR) to HIV antigens, associated with control of HIV replication, are rarely restored in patients starting HAART during chronic infection. ACTG 5046 examined the effects of IL-2 administration on responses to HIV and tetanus immunization. |
| 109. | INTERLEUKIN-2 THERAPY IN HIV-1 INFECTED ARV NAÏVE PATIENTS: EFFECT ON T CELL ACTIVATION. Sullivan A, Amjadi P, Nelson M, Tavel J, Gotch F, Youle M, Gazzard B Abstract: CD4 and CD8 activation markers rose acutely and transiently following IL-2 therapy in HIV-1 infected patients not receiving HAART, returning to baseline within 4 weeks. |
| Session 21, Oral: Salvage Therapy Tuesday, July 10th |
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| 110. | VIROLOGICAL AND IMMUNOLOGICAL EFFECTS OF DISCONTINUATION OF ANTIRETROVIRAL THERAPY IN HIV-POSITIVE PATIENTS WITH VIROLOGICAL FAILURE AND A CD4 COUNT ABOVE 500 CELLS/ML Mussini C, Bugarini R, Perno C, Antinori A, Borghi V, Cossarizza A, Esposito R Abstract: This study shows that if antiretroviral therapy is discontinued in patients with virological failure and a high CD4 count in most of them there is a rapid and severe decrease in CD4 count. |
| 111. | IMPACT OF TREATMENT INTERRUPTION ON PLASMA VIRAL LOAD, CD4 COUNT AND VIRTUAL PHENOTYPES (VIRCO) IN HIV PATIENTS WHO FAILED MULTIPLE COURSES OF ANTIRETROVIRAL THERAPY. Tesiorowski A, Harris M, Harrigan R, O'shaughnessy M, Montaner J Abstract: To assess changes in plasma viral load (VL), CD4 percentage, absolute CD4 count and Virtual Phenotypes_ following interruption of therapy in a cohort of heavily pretreated individuals. |
| 112. | INDINAVIR INTENSIFICATION FOR SALVAGE THERAPY IN HIV INFECTED PATIENTS HEAVILY PRE-TREATED : INDINAVIR/RITONAVIR BID 800/200 MG VS 400/400 MG Mallolas, J; Blanco, J; Sarasa, M; Arnedo, M; López-Púa, Y; Martínez, E; Milinkovic, A; García-Viejo, M; Pumarola, T; Gatell, J Abstract: Patients treated with Ind 800 mg TID can be rescued with Ind/Rtv. Ind/Rtv 800/200 mg BID seems to be better than 400/400 mg BID in terms of virological efficacy and tolerance. |
| 113. | PRELIMINARY RESULTS OF A RANDOMIZED TRIAL COMPARING D4T/DDI/ABACAVIR/EFAVIRENZ TO THE SAME COMBINATION PLUS HYDROXYUREA WITH OR WITHOUT IL-2 AS SALVAGE REGIMENS (THE HYDILE STUDY) Lafeuillade A, Chadapaud S, Hittinger G, Miara A, Baconnet A, Poggi C Abstract: Our objective was to evaluate the efficacy of a RTI regimen, with or without Hydroxyurea (HU) and Interleukin-2 (IL-2), in HIV-infected pts failing PI-containing regimens. |
| 114. | MULTIPLE DRUG RESCUE THERAPY (MDRT) WITH AND WITHOUT LOPINAVIR/R (LPV/R) Harris M, Yip B, Hogg R, Harrigan R, Montessori V, O'shaughnessy M, Montaner J Abstract: To determine the impact of the availability of LPV/r on the antiviral response to MDRT regimens among heavily pretreated patients. |
| 115. | ANTIVIRAL ACTIVITY AND TOLERABILITY OF PEG-INTRON IN HIV-INFECTED PATIENTS FAILING HAART. Nieto, L; Angel, J; Gazzard, B; Cahn, P; Ward, D; Ramirez-Ronda, C; Taglietti, M; Greaves, W Abstract: PEG-Intron may have a therapeutic role in the treatment of HIV-infected patients failing HAART. Further studies in combination with optimized HAART are warranted. |
| Session 22, Oral: Viral Replication: New Insights Tuesday, July 10th |
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| 116. | DYNAMICS OF HIV BINDING AND ENTRY DETERMINED BY TIME-LAPSE FLUORESCENT MICROSCOPY REVEAL THAT HIV IS MORE INFECTIOUS THAN IS CURRENTLY BELIEVED. David McDonald, Heather Feltman, Devon Mann, and Thomas J. Hope Abstract: Finally, the ghost cells used in our study allow infection of the cells to be determined. Quantitation of virus binding per cell relative to infection reveals that the potential for each virion to successfully infect a cell is much greater than previously reported. Therefore, the current supposition that vast majority of virions of HIV are inherently noninfectious is incorrect. |
| 117. | Abstract: Not submitted. |
| 118. | ASSEMBLY AND MOVEMENT OF GAG/GAG-POL COMPLEXES IN HIV-INFECTED CELLS. Halwani R, Khorchid A, Wainberge M, Kleiman L Abstract: We have detected the cytoplasmic interaction between Pr55gag and Pr160gag-polin HIV-1 using antibody to integrase (anti-IN) to coimmunoprecipitate both Pr55gag and Pr160gag-polfrom lysates of COS-7 and 293T cells transfected with wild-type and mutant HIV-1 proviral DNA. |
| 119. | THE TRIPEPTIDES GPG-NH2 AND ALG-NH2 INTERFERE WITH HIV-1 BUDDING AND CAPSID ASSEMBLY: A NEW STRATEGY FOR ANTIVIRAL THERAPY Vahlne A, Su J, Höglund S, Sandin Reneby S, Goobar-Larsson L, Nyström I, Végvári A Abstract: Treatment with tripeptide amides interfering with virus capsid assembly represents a new startegy for antiviral therapy. GPG-NH2 is efficiently adsorbed from the gut by the pept1/pept2 oligopeptide transport system, as observed in both in vitro (Caco-2 cells) and in vivo (experimental anials and man). GPG-NH2 has also been shown to decrease viral loads in a small phase I/II clinical study and is presently undergoing a phase II clinical study at ten different centers in Europe. |
| 120. | CD147 FACILITATES HIV-1 INFECTION BY INTERACTING WITH VIRUS ASSOCIATED CYCLOPHILIN A Bukrinsky M, Pushkarsky T, Yurchenko V, Zybarth G, Sherry B Abstract: Cyclophilin A (CypA) is a ubiquitously distributed protein with both intracellular (protein folding) and extracellular (chemotactic) activities. |
| 121. | INTERFERON REGULATORY FACTORS REGULATE ACTIVATION OF HIV-1 VIA PHYSICAL AND FUNCTIONAL INTERACTIONS WITH TAT Battistini A, Sgarbanti M, Borsetti A, Moscufo N, Marziali G, Coccia E, Ensoli B Abstract: Our results identify IRF-1 as a cellular transcription factor essential for efficient HIV-1 gene expression and viral replication and indicate that the recruitment of IRF-1 to the HIV-1 promoter can be a key step in the early phases of infection or during viral reactivation from latency, in response to both viral infection and cell activation signals. |
| Session 26, Oral: Oral Resistance Wednesday, July 11th |
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| 122. | EVOLVING PATTERNS OF HIV-1 RESISTANCE TO ANTIRETROVIRAL AGENTS IN NEWLY INFECTED INDIVIDUALS Simon V, Vanderhoeven J, Hurley A, Louie M, Parkin N, Boden D, Markowitz M, Ramratnam B, Dawson K Abstract: For the years 1999-2000 we found an increased number of both transmitted drug resistant HIV-1 variants and viruses with altered genotypes in RT but wild-type phenotypes. |
| 123. | EVOLUTION OF HIV-1 RESISTANCE MUTATIONS TO NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTI) FOLLOWING WITHDRAWAL Joly V, Descamps D, Zeng F, Touati F, Mentre F, Yeni P, Brun-Vezinet F Abstract: To study the evolution of NNRTI resistance mutations after withdrawal of this class of drugs, in patients (Pts) who experienced virological failure when receiving a NNRTI containing antiretroviral combination therapy. |
| 124. | BOTH ANTIRETROVIRAL DRUG LEVELS AND DRUG RESISTANCE ARE ASSOCIATED WITH SHORT-TERM VIROLOGIC RESPONSES TO SUBSEQUENT DRUG REGIMENS IN CPCRA 046 (GART STUDY) Mayers D Abstract: To determine the short-term virological impact of plasma antiretroviral (AR) drug levels and baseline HIV drug resistance on the response to the next antiretroviral regimen for patients (pts) failing on a PI-containing regimen. |
| 125. | THE VIRTUAL PHENOTYPE IS A SUPERIOR INDEPENDENT PREDICTOR OF CLINICAL RESPONSE THAN GENOTYPING WITH A COMMON RULES BASED INTERPRETATION Larder B, Peeters M, Verbiest W, Harrigan R, Graham N Abstract: Retrospective studies have correlated baseline drug resistance (phenotype and genotype) with clinical response. |
| 126. | IMPACT OF TREATMENT GUIDED BY PHENOTYPIC OR GENOTYPIC RESISTANCE TESTS ON THE RESPONSE TO ANTIRETROVIRAL THERAPY (ART): FINAL ANALYSIS OF THE NARVAL TRIAL (ANRS 088) Meynard J, Vray M, Morand-Joubert L, Peytavin G, Brun-Vezinet F, Clavel F, Girard P Abstract: To evaluate the respective value of phenotype (P) and genotype (G) for choosing optimal ART vs by standard of care (SOC) in patients (pts) failing protease inhibitor (PI) containing regimen with VL<1000 cp/ml. |
| 127. | CCTG 575: A RANDOMIZED, PROSPECTIVE STUDY OF PHENOTYPE TESTING (PHENO) VERSUS STANDARD OF CARE (SOC) FOR PATIENTS FAILING ANTIRETROVIRAL THERAPY (ARV) Haubrich R, Keiser P, Kemper C, Witt M, Leedom J, Forthol D, Hellmann N Abstract: To compare PHENO (ViroLogic assay) to SOC to improve virologic response to ARV. |
| 128. | GENOTYPIC ANALYSES AND HIV RNA RESPONSES IN PATIENTS AFTER 96 WEEKS OF TENOFOVIR DF (TDF) THERAPY Miller M, Johnson A, Isaacson E, Margot N Abstract: Study 902 was a placebo-controlled, 48-wk phase II study of 3 doses of TDF when added to stable ART in 189 treatment-experienced pts (mean 4.6 yrs prior ART, 94% with NRTI-associated mutations). |
| 129. | COMPARISON OF THE EMERGENCE OF GENOTYPIC RESISTANCE OVER 48 WEEKS OF THERAPY WITH ABT-378/R (KALETRAT) OR NELFINAVIR PLUS D4T/3TC Kempf D, Bernstein B, King M, Moseley J, Gu K, Cernohous P, Sun E Abstract: There were no significant differences in the duration or level of detectable viremia, or in adherence (as measured by pill counts), between treatment arms in the subjects with available genotype. These results suggest that the genetic barrier to resistance to Kaletra in treatment-naïve subjects is higher than the barrier to NFV resistance. Data through Week 60 will be presented. |
| Session 27, Oral: Pediatrics and MTCT Wednesday, July 11th |
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| 130. | VERTICALLY ACQUIRED HIV INFECTION - WHERE DO WE GO FROM HERE? Marie-Louise Newell Abstract: Questions remain about the management of women identified as infected late in pregnancy or during delivery, about the effect on the risk of vertical transmission of drug resistance, therapy for the neonates of women who already receive HAART and for children infected despite ART prophylaxis. Quality of life of infected children and mothers needs further improvement. |
| 131. | MATERNAL VIRAL DIVERSITY, V3 ANTIBODIES AND THE VERTICAL TRANSMISSION OF HIV-1 SUBTYPE C. Guevara H, Tien P, Johnston E, Zijenah L, Contag C, Hendry M, Katzenstein D Abstract: Increased diversity in the envelope (env) V3 region of HIV has been associated with clinical non-progression and reduced mother to child transmission (MTCT). |
| 132. | EFFECT OF HIV-1 RNA LEVELS, CD4+ LYMPHOCYTES AND CHEMOKINE RECEPTOR GENE POLYMORPHISMS ON THE RESPONSE TO HAART IN HIV-1 INFECTED CHILDREN Bologna R, Mangano A, Mecikovsky D, Battalla M, Sarkis C, Kopka J, Sen L Abstract: Plasma HIV-1 viral load (pVL) and CD4+ lymphocytes are independent predictors of disease progression in children with HIV-1 infection. |
| 133. | EARLY SPREAD OF HIV-1 B/F RECOMBINANT INTERSUBTYPE IN CHILDREN BORN TO INFECTED MOTHERS IN ARGENTINA Gomez Carrillo M, Avila M, Pando M, Martinez Peralta L, Russell K, Carr J Abstract: In Argentina, the first AIDS case was detected in 1982. HIV-1 sequences reported during early ´90 showed a predominance of subtype B. |
| 134. | HOST GENETIC AND IMMUNLOGIC RESPONSES MEDIATING LONG TERM SURVIVAL IN HIV-1-INFECTED AFRICAN CHILDREN Chakraborty R, Sutton J, Appay V, Otsyula M, D'agostino A, Rowland-Jones S Abstract: The magnitude, specificity and functional phenotype of HIV-1-specific CD8-T-Lymphocyte (CTL) and CD4 responses were studied among 49 HIV-1-infected African children. |
| 135. | EFFECT OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY IN INFANTS UPON IMMUNE RECONSTITUTION Pahwa S, Kharbanda M, Chavan S Abstract: These findings implicate residual immune perturbations in HIV infected infants given HAART early in life that persist despite increase in TRECs, virologic suppression and normal CD4 T cell counts. |
| 136. | ATYPICAL HIV-1 ASSOCIATED HEMOLYTIC UREMIC SYNDROME (HIV-HUS) AND HIV-HELPP SYNDROME IN CHILDREN Ray P, Chandra R, Selby D, Rakusan T Abstract: HIV-HUS is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Very little is known about the pathogenesis of HIV-HUS in children. |
| Session 28, Oral: Current Controversies in Immunopathogenesis Wednesday, July 11th |
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| 137. | MECHANISMS OF CD4+ T CELL DEPLETION M.D. Hazenberg, S.A. Otto, R.A. Coutinho, W. Fibbe, D. Hamann, R.J. de Boer, F. Miedema Abstract: HIV-1 infection is characterized by hyperactivation of the immune system. This may appear to be a key factor, as less-pathogenic HIV-2 infection or natural host SIV infection do not elicit such immune hyperactivation. |
| 138. | THE THYMUS AND HIV INFECTION. Michael Lederman Abstract: The increasing occurrence of lymphocyte depletion states has increased interest and opportunity to examine the role of the thymus in cellular homeostasis and function. While thymic function is not essential in healthy adults, thymic T cell maturation likely plays a key role in maintainingand restoring T cell numbers during lymphocyte depletion. Adult human thymic tissue is rarely accessible, thus studies of thymic function are largely dependent upon indirect measurements or models. |
| 139. | IMMUNE CONTROL OF HIV INFECTION Walker, B. Abstract: Not submitted. |
| 140. | SKEWED MATURATION OF MEMORY HIV-SPECIFIC CD8 T LYMPHOCYTES G. Pantaleo Abstract: These results demonstrate a selective impairement of the differentiation of HIV-specific memory CD8+ T cells. Additional results regarding the distribution and function of the different populations of memory CD8 HIV- and CMV-specific T cells in other anatomic compartments such as lymphoid tissue will be also presented. |
| 141. | IMPACT OF INTERLEUKIN-2 ON THE TURNOVER OF T LYMPHOCYTES Cliff Lane Abstract: The immune systems of patients with untreated HIV infection are characterized by a CD4+ T cell lymphopenia occurring in the setting of a polyclonal activation of T and B lymphocytes. The increase in T cell turnover is directly related to viral load and decreases promptly upon initiation of antiretroviral therapy. The intermittent administration of interleukin-2 (5 days every 8 weeks) can lead to significant increases in CD4+ T cell numbers. |
| Session 29, Oral: Molecular Epidemiology and Viral Diversity Wednesday, July 11th |
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| 142. | MOLECULAR EPIDEMIOLOGY AND GLOBAL DIVERSITY OF HIV-1 McCutchan, F; Carr, J; Robb, M; Birx, D. Abstract: In this era of field efficacy testing of candidate vaccines, it will be critically important to identify incident strains in cohorts, to define appropriate vaccine candidates, and to fully characterize the inter-current HIV-1 infections in both vaccine and placebo groups. |
| 143. | VIRAL INFECTIVITY, REPLICATION, AND QUASISPECIES EVOLUTION OF HIV-1 IN PRIMARY INFECTION Petrella M, Brenner B, Spira B, Routy J, Wainberg M Abstract: In this study, we are continuing research to evaluate the relative replicative competence of dual and triple class multidrug resistant viruses acquired during primary HIV infection. |
| 144. | GENETIC DIVERSITY IN HIV-1 FROM BUENOS AIRES: IDENTIFICATION OF RECOMBINANT B/F VARIANTS AND IMPLICATIONS ON RESISTANCE TO ANTIRETROVIRAL DRUGS. Petroni A, Coviello S, Illescas E, Deluchi G, Pereda G, Benetucci J, Garberi J Abstract: there is a relevant prevalence of recombinants B/F among HIV Pts from Buenos Aires. The genetic background and the Freq of several resistance associated mutations seem to be strongly linked. |
| 145. | SURVEILLANCE FOR HIV-1 SUBTYPES IN SOUTH AMERICA Russell K, Negrete M, Sanchez J, Sanchez J, Avila M, Cuchi P, Carr J Abstract: The objective of our surveillance program is to describe the molecular epidemiology of HIV-1 subtypes in South America (SA). |
| 146. | FULL GENOME SEQUENCES OF FIVE DIFFERENT HIV-1 RECOMBINANTS BETWEEN SUBTYPE B AND CRF01_AE FROM SOUTHEAST ASIA Watanaveeradej V, Tovanabutra S, Carr J, Benenson M, Brown A, Birx D, McNeil J, Mc Cutchan F Abstract: HIV-1 BE intersubtype recombination has begun in Thailand. Two of the cases were incident infections. The samples range from 1990 to 2000. The impact of recombination on vaccine trial plans should be assessed. |
| 147. | BF INTER-SUBTYPE RECOMBINANTS OF HIGHLY SIMILAR BUT NOT IDENTICAL STRUCTURE RECOVERED FROM ARGENTINA, URUGUAY AND BOLIVIA AND CHARACTERIZED BY FULL GENOME ANALYSIS. Carr J, Avila M, Gomez Carrillo M, Negrete M, Gianella A, Andrade R, Russi J, Russell K Abstract: To more fully describe the genetic diversity of HIV-1 in South America by full genome sequencing. |
| 148. | PREVALENCE OF THE CODON 333 RESISTANCE GENOTYPE IN NAÏVE AND PRE-TREATED PATIENTS IN SPAIN. Gallego O, Corral A, Rodés B, Soriano V Abstract: A substitution at codon 333 (G_D/E) within the RT gene causes resistance to both AZT and 3TC, in a background of mutations associated with loss of sensitivity to AZT. Although the M184V restores the sensitivity to AZT in viruses harboring AZT-resistant genotypes, the 333 mutation annuls this benefit. We have examined in what extent subjects failing antiretroviral therapy harbor the codon 333 mutation. |
| Session 30, Oral: Oral Prevention Wednesday, July 11th |
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| 149. | PREVENTION OF HIV INFECTION: STD CONTROL AND ART INTERVENTION Kenneth Mayer Abstract: The wider use of ART and more effective STD control should help to slow the spread of HIV and should be considered as important public health measures, but protocols will need to be carefully developed for specific community situations. The relative cost-benefits of each strategy deserves further study, to assess sustainability, the development of antimicrobial resistance, and effects on risk taking behavior. |
| 150. | POSTEXPOSURE PROPHYLAXIS: WHERE DO WE GO FROM HERE? Denise M. Cardo Abstract: Other challenges are the completion of follow-up evaluation and management of exposures to sources co-infected with hepatitis C virus. Future directions in the area of prevention and management of occupational HIV infection include, for example, better preventive measures and safer postexposure prophylaxis. |
| 151. | POSTEXPOSURE PROPHYLAXIS AFTER OCCUPATIONAL HIV EXPOSURES: THE EXPERIENCE AT 47 NATIONAL SURVEILLANCE SYSTEM FOR HEALTHCARE WORKERS HOSPITALS, 1996-2000 Beltrami E, Hellmuth K, Srivastava P, Cardo D Abstract: In June 1996, the U.S. Public Health Service first recommended postexposure prophylaxis (PEP) after certain occupational HIV exposures. |
| 152. | FREQUENCY, PATTERNS AND CORRELATES OF HIV TRANSMISSION RISK BEHAVIORS AMONG HIV SEROPOSITIVE PATIENTS IN CLINICAL CARE Friedland Gh, Fisher J, Fisher W, Amico R, Cornman D Abstract: HIV+ patients (pts) receiving antiretroviral therapy (ART) who engage in risk behavior may transmit new and resistant HIV infections. |
| 153. | SIDE EFFECTS ASSOCIATED WITH POST-EXPOSURE PROPHYLAXIS IN A POPULATION BASED SETTING Braitstein P, Chan K, Beardsell A, McLeod A, Montaner J, O'Shaughnessy M, Hogg R Abstract: Our analysis suggests that people on triple combination post-exposure prophylaxis experience more gastrointestinal, liver, and neuropathic side effects. This data also indicates that women and individuals who were exposed occupationally are more likely to experience side effects. |
| 154. | BEHAVIORAL IMPACT OF THE AVAILABILITY OF POST-SEXUAL-EXPOSURE CHEMOPROPHYLAXIS (PEP) FOR HIV: A PROSPECTIVE COHORT STUDY Schechter M, Lago R, Moreira R, Mendelsohn A, Harrison L Abstract: There are limited data on effectiveness and behavioral impact of PEP to prevent HIV infection. PEP could increase the risk of HIV infection if its availability resulted in increased high-risk behavior. |
| Late-Breakers | |
| Session 33, Oral: Late Breakers Wednesday, July 11th |
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| LB-O1. | COMPETITION ASSAYS CLEARLY INDICATES THAT SUBTYPE C HIV-1 ISOLATES ARE LESS THAN FIT THAN ISOLATES OF OTHER SUBTYPES Arts, E; Ball, S; Quinones-Mateu, J; Marozsan, A. Abstract: Subtype C |