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14th Conference on Retroviruses and Opportunistic InfectionsLos Angeles, Calfornia - February 25-28, 2007 |
Cite as: Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14:abstract no. xx
| Session 1—Workshop Program Committee Workshop for New Investigators and Trainees |
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| 1a | Opening Comments Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 1a) John Mellors Abstract not currently available |
| 1b | Origins of HIV-1 and Viral Diversity Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 1b) Beatrice Hahn Abstract not currently available |
| 1c | Host Restriction Factors Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 1c) Michael Malim Abstract not currently available |
| 1d | New Insights into HIV Pathogenesis Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 1d) Ronald Swanstrom Abstract not currently available |
| 1e | Host Immunity and Prospects for an HIV Vaccine Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 1e) Richard Koup Abstract not currently available |
| 1f | Changing Patterns of US and Global Epidemiology Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 1f) Kevin De Cock Abstract not currently available |
| 1g | Optimizing Maternal and Pediatric Care Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 1g) Elaine Abrams Abstract not currently available |
| 1h | Current and Future ART Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 1h) Robert Schooley Abstract not currently available |
| 1i | Management of Chronic Viral Hepatitis in HIV-infected Persons Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 1i) David Thomas Abstract not currently available |
| 1j | Closing Comments Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 1j) Scott Hammer Abstract not currently available |
| Session 3—Workshop Genomics Workshop: How to Investigate Host-HIV Interactions |
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| 3a | SEARCHING THE GENOME FOR DETERMINANTS OF RESPONSE TO HIV Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 3a) David Goldstein1, K Shianna1, and A Telenti2 Here I describe these analysis tools and illustrate their use in a whole genome association study seeking to identifying genes influencing set point, making use of both samples from the MACS cohort and a new cohort, called EuroChavi, that has been developed as a collaboration between CHAVI and multiple European cohorts. I conclude with discussion of how CHAVI plans to integrate the analyses of different phenotypes related to how individuals respond to infection with HIV. |
| 3b | GENOTYPING TECHNOLOGIES: SMALL- AND LARGE-SCALE STUDIES Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 3b) Kevin Shianna The use of these tagging arrays will be discussed focusing specifically on genomic coverage of the specific arrays and the use of these arrays to detect deletions and duplications, commonly referred to as copy number variations (CNV). The genome-wide identification of CNV on a large scale is now possible through the use of high-density SNP based arrays. It is highly probable that some CNV will be associated with certain complex diseases or traits. Therefore, it is essential that the identification of these variants play a role in genome-wide association studies. Lastly, small-scale association studies and a SNP-based HLA typing array for use in the CHAVI host genetic studies will be discussed. |
| 3c | PRACTICAL APPLICATIONS IN HIV DISEASE Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 3c) Amalio Telenti The likelihood of using genetic data for drug development, for the analysis of vaccine response, or for clinical use depends on a concerted effort to establish evidence, to validate through clinical trials, and to generate cost-effective tools. |
| 3d | INTRINSIC IMMUNITY AGAINST RETROVIRUSES IN PRIMATE GENOMES: EVOLUTIONARY RETROSPECTIVES AND PROSPECTIVES Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 3d) Harmit Malik and M Emerman 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. I will describe our techniques and studies for such identifications. |
| 3e | GENETIC COHORTS AND APPLICATIONS IN PHARMACOGENETICS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 3e) David Haas Because of the well-recognized risk of false discovery due to multiple comparisons in high-throughput human genomic association studies, such repositories are critical both for the initial identification of potential genotype-phenotype associations, and for validation of initial putative associations. Through continued translational and applied research, pharmacogenomics will ultimately benefit persons living with HIV worldwide by identifying new targets for novel therapeutics, through individualized drug prescribing that is informed by human genetic testing, and by anticipating the likely frequency of adverse treatment events among diverse populations worldwide based on knowledge of genetic architecture. |
| Session 4—Symposium New and Emerging Retroviruses |
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| 4 | SIV INFECTION IN WILD GORILLAS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 4) Martine Peeters Additional field studies are needed to determine the overall prevalence, subspecies association, genetic diversity, and natural history of SIVgor infection in wild gorillas. It will also be important to determine by what route gorillas acquired SIVgor, since these apes are herbivores, and physical encounters between gorillas and chimpanzees are believed to be rare. Gorillas are hunted for food and medicinal uses; the present findings suggest that such practices may have been responsible for the HIV-1 group O zoonosis and could pose an ongoing risk to humans. |
| 5 | SIMIAN FOAMY VIRUS INFECTION OF HUMANS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 5) Antoine Gessain1, S Calattini1, E Betsem2, A Froment3, P Mauclere1,4, P Tortevoye1, C Schmitt1, R Njouom4, and A Saibo5 These data demonstrate a high and efficient transmission of SFV to humans in natural settings in Central Africa specifically following severe bites by apes, and the viral persistence over several decades in the new human host. |
| 6 | EMERGENCE OF NOVEL HUMAN T-LYMPHOTROPIC VIRUSES Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 6) William Switzer These results demonstrate greater HTLV diversity than previously recognized and suggest ongoing STLV transmission in humans exposed to nonhuman primates. Expanded surveillance and longitudinal clinical studies are needed to better define the epidemiology and public health importance of HTLV-3 and HTLV-4 infections. |
| 7 | LONG-TERM NON-PROGRESSION WITH HIV INFECTION: LESSONS FROM HIV-2 Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 7) Sarah Rowland-Jones Data will be presented from recent immunological and virological studies in cohorts of HIV-2-infected donors in the Gambia and Guinea-Bissau, West Africa. The HIV-2-infected LTNP have preserved HIV-specific T-helper responses, characterized by interleukin-2 (IL-2) production and proliferation, and are distinguished by strong responses toward a highly conserved region of the HIV-2 gag protein. Understanding the basis of delayed disease progression in the majority of HIV-2-infected people should provide insights into the key requirements for protective immunity against HIV infection. |
| Session 5—Symposium Urgent Issues in the Developing World |
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| 8 | TRANSMISSION OF EXTENSIVELY DRUG-RESISTANT TB IN SOUTH AFRICA AND IMPLICATIONS FOR INFECTION CONTROL IN HEALTH CARE SETTINGS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 8) Karin Weyer Appropriate infection control in high HIV-prevalence settings is of paramount concern. The risk of XDR-TB transmission in such environments require immediate and urgent intervention, including early detection of TB drug resistance, segregation of infectious patients, use of appropriate personal respiratory protection, a rapid response to outbreak situations, and urgent implementation of appropriate infection control interventions. The development of appropriate standards for facility design, environmental infection control measures and functional methods for in-house risk assessment and management to prevent airborne infection are also urgently needed. |
| 9 | A LARGE OUTBREAK OF DIARRHEA AMONG NON-BREASTFED CHILDREN IN BOTSWANA, 2006--IMPLICATIONS FOR HIV PREVENTION STRATEGIES AND CHILD HEALTH Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 9) Tracy Creek1, W Arvelo1, A Kim1, L Lu1, A Bowen1, O Mach1, T Finkbeiner1, L Zaks1, J Masunge2, and M Davis1 During a multi-pathogen outbreak of diarrhea in Botswana, non-breastfed children under 2 years old were most affected, and malnutrition contributed to high mortality. Careful attention to water quality, sanitation, hygiene, and nutrition is essential for children who are not breastfeeding. Support for increased breastfeeding among HIV-positive and HIV-negative women may reduce the risk of another serious outbreak. |
| 10 | EVOLUTION OF COUNSELING AND TESTING POLICY AND PRACTICE IN SUB-SAHARAN AFRICA: IMPLICATIONS FOR IMPROVING ACCESS TO HIV PREVENTION AND CARE Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 10) Nafuna Wamai1, M Achom1, D Kabatesi1, R Wanyenze2, and R Bunnell3 To achieve WHO’s goal of universal access to HIV prevention, care, and treatment, millions of people in Sub-Saharan Africa will need access to HIV testing. This will require a major scale-up of HCT and care services, diversification of HCT approaches, improved diagnosis among children and infants, and progressive policies that support innovation while preserving quality. |
| 11 | PMTCT OF HIV IN RESOURCE-POOR SETTINGS - WHY ARE WE DOING SO BADLY? Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 11) Marc Bulterys To reduce global MTCT of HIV by 50% by the year 2010, a radical increase in access to HIV testing and counseling and in PMTCT coverage is necessary in resource-poor settings. Rapid scale-up of PMTCT services and provision of comprehensive, family-centered HIV care and treatment for women, children and their families are global priorities. The public health response must include effective linkages between PMTCT, ART, and family planning services. Ultimately, primary HIV prevention in young women and men holds the key to PMTCT. |
| Session 7—Plenary Prevention of HIV Transmission from Breastfeeding |
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| 13 | PREVENTION OF HIV TRANSMISSION FROM BREASTFEEDING Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 13) Hoosen Coovadia1, A Coutsoudis2, N Rollins2, R Bland3, and M Newell3 The role of innate immunity, antibodies, cellular reservoirs, and free virus in the pathogenesis of breast-milk transmission will be highlighted. Interventions potentially useful to reduce breastfeeding transmission of HIV will be identified. These include: primary HIV prophylaxis for women, chemo- and immuno-prophylaxis, infant nutrition policies, and feeding options. For example, a number of African studies have shown that exclusive breastfeeding is associated with a lower HIV transmission than mixed breastfeeding; exclusive breastfeeding by HIV-positive women is accompanied by a lower infant morbidity and mortality. |
| Session 8—Plenary Pathogenesis of AIDS - Connecting Viral Replication to Disease in the Non-Human Primate Model |
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| 14 | PATHOGENESIS OF AIDS - CONNECTING VIRAL REPLICATION TO DISEASE IN THE NON-HUMAN PRIMATE MODEL Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 14) Louis Picker Proliferative failure within and gradual depletion of these central memory populations appears to be the primary determinant of rapid and chronic onset AIDS, respectively. This talk will examine the likely mechanisms involved in CD4+ central memory T cell “failure,” and discuss the implication of the “2-step threshold” hypothesis for development of new immunotherapeutic interventions in this disease. |
| Session 9—Oral Abstracts Host-Cell Regulation of Viral Replication |
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| 15 | VIRUS EVOLUTION REVEALS LEDGF/p75 AS THE SOLE MEDIATOR OF CHROMOSOMAL TETHERING Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 15) Zeger Debyser, A Hombrouck, J De Rijck, L Vandekerckhove, J Hendrix, Y Engelborghs, F Christ, and M Witvrouw Our data provide biological relevance to the previously resolved structure of the LEDGF/p75 integrase interface. Demonstration of the exclusive role of LEDGF/p75 in HIV integration justifies efforts in developing small molecule inhibitors targeting the interaction between integrase and LEDGF/p75. |
| 16 | MECHANISM OF TRIM5α RESTRICTION Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 16) E Campbell1, J Anderson1, A Joseph1, N Vandegraaf2, A Engelman2, and Thomas Hope1 We propose that the TRIM5α proteins restrict by encapsidating the incoming viral core, altering trafficking of the reverse transcribing viral cDNA to the nucleus and targeting the reverse transcription complex for disruption involving the proteasome. |
| 17 | WHOLE GENOME ANALYSIS IDENTIFIES A SUSCEPTIBILITY LOCUS TO HIV-1 Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 17) Corinne Loeuillet1, S Deutsch2, P Taffé3, M Rotger1, J Beckmann4, S Antonarakis2, and A Telenti1 We identified, using a multistep procedure involving unbiased whole-genome linkage scan followed by association studies, a novel locus on chromosome 8 that influences human susceptibility to HIV-1. This is the first time a quantitative trait locus initially mapped by in vitro approaches, has also been shown to be relevant in a clinical setting. |
| 18 | IDENTIFICATION AND CHARACTERIZATION OF VIRAL MICRORNA ENCODED BY 2 AIDS-RELATED OPPORTUNISTIC HERPESVIRUSES Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 18) Xuezhong Cai1, A Schäfer1, S Lu1, B Damania2, N Raab-Traub2, and B Cullen1 For the first time, we report the identification of an array of KSHV and EBV miRNA from latently infected cells. EBV-encoded BART miRNA are highly expressed in nasopharyngeal carcinoma cells while BHRF miRNA can only be detected in B cells at latency phase III. These viral miRNA may play a critical role in the maintenance of the viral life cycle and virus-induced tumorgenesis. |
| 19 | HIV-1 INFECTION UNLEASHES RETROTRANSPOSITION OF ENDOGENOUS ELEMENTS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 19) Brad Jones1, K Garrison2, N Anwar1, D Meiklejohn3, L Ndhlovu2, D Nixon2, and M Ostrowski1 While HERV-K, LINE-1, and AluSX transcripts are expressed in healthy ex vivo PBMC, a post-transcriptional block prevents retrotransposition. HIV-1 infection in vitro results in the retrotransposition of HERE in infected cells. The discovery of a LINE-1 insertion into a primary isolate HIV-1 sequence demonstrates the co-existence of LINE-1 and HIV-1 retrotransposition activity and provides evidence for a similar in vivo induction. The association of retrotransposition activity with HIV-1 infection suggests new mechanisms for HIV-1-related pathologies. |
| 20 | 7SL RNA IS A CO-FACTOR OF THE ANTIVIRAL CYTIDINE DEAMINASE APOBEC3G Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 20) Tao Wang, C Tian, K Luo, T Sarkis, Y Yu, and X F Yu Thus, 7SL RNA, which is encapsidated into diverse retroviruses, is a key co-factor of the antiviral A3G. Selective interaction of A3G with certain Pol-III-derived RNA raises the question of whether A3G and its co-factors may have yet-unidentified cellular functions. |
| Session 10—Oral Abstracts Pathogenetic Factors Affecting HIV-Specific Immune Responses |
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| 21 | SUPERINFECTION SUSCEPTIBILITY AND LOW NEUTRALIZING SERUM RESPONSES IN TREATED PERSONS WITH SUPPRESSED PLASMA VIRAL RNA LEVELS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 21) J McConnell1, T Wrin2, Y Liu2, C Kreis1, L Bragg1, F Hecht3, N Parkin2, Robert M Grant1,3 Multiple infections suggestive of superinfection were observed frequently in groups having negligible serum neutralizing levels, including those with suppressed viral load on therapy and those in the first 3 years of primary infection. Broad serum neutralization including partner-derived viruses may block superinfection or prevent systemic spread of additional infections. |
| 22 | SPECIFIC AMINO ACIDS IN THE N-TERMINUS OF THE gp41 ECTODOMAIN CONTRIBUTE TO THE STABILIZATION OF A SOLUBLE, CLEAVED gp140 ENVELOPE GLYCOPROTEIN FROM HIV-1 Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 22) Antu Dey, K David, P Klasse, and J Moore Modifications of a few selected amino acids in the N-terminal region of gp41 can improve the stability of gp140 trimers, without impairing the exposure of various neutralizing antibody epitopes. This finding is generalizable to multiple HIV-1 genotypes and hence might be useful for neutralizing antibody-based vaccine strategies based on the use of this type of immunogen. |
| 23 | PRESENCE OF HLA CLASS I-ASSOCIATED CYTOTOXIC T LYMPHOCYTE ESCAPE MUTATIONS IN CHRONIC UNTREATED HIV INFECTION IS SIGNIFICANTLY CORRELATED WITH CLINICAL MARKERS OF MORE SEVERE DISEASE PROGRESSION Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 23) Zabrina Brumme1,2, C Brumme1,2, C Kadie3, J Carlson3, C Chui2, T Mo2, J Montaner2, B Walker1, D Heckerman3, and P Harrigan2 Selected in vivo CTL escape mutations occurring in response to HLA-mediated selection pressure are common and reproducible enough to be detected on a population level, and are observed with exceptional density in Nef compared with PR/RT. Presence of escape mutations in Nef and PR/RT is associated with more severe HIV disease progression. |
| 24 | RELATIONSHIP BETWEEN HLA GENOTYPE AND THE FUNCTIONAL PROFILE OF ANTIGEN-SPECIFIC CD8 T CELLS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 24) Alexandre Harari1, C Cellerai1, J Kostler2, S Gaudieri3, I James3, M John3, R Wagner2, S Mallal3, and G Pantaleo1 These results provide new insights into the associations between HLA restriction, TCR avidity, PD-1 expression, and the functional profile of virus-specific CD8 T-cell responses. Furthermore, they provide the rationale for the protective role of HLA-B in HIV-1 infection. |
| 25LB | A POLYMORPHISM IN THE FcγRIIIa GENE IS ASSOCIATED WITH HIV INFECTION RISK Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 25LB) Donald Forthal, G Landucci, and T Phan FcγRIIIa appears to be an HIV-1 restriction gene that confers a heterozygous disadvantage. The association between FcγRIIIa genotype and infection risk is striking because it implies that virus or infected cells opsonized with antibody (the ligand for FcγRIIIa) are key determinants of successful infection. The antibody is likely to be donor-derived, but could also be a pre-existing, recipient antibody that binds to virions or infected cells. |
| 26 | PROTECTIVE HLA CLASS I ALLELES SELECT HIV-1 MUTANTS AND SLOW DISEASE PROGRESSION Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 26) John Frater1, H Brown1, A Oxenius2, H Gunthard3, C Brander4, P Kiepiela5, B Walker4,5 P Goulder4,6, A McLean6, and R Phillips1 We conclude that protective HLA Class I alleles drive out significant variation in the epitopes they target, but in conjunction with persisting immune responses to the equivalent wild-type peptides. We hypothesise that escape from these beneficial HLA molecules confers a fitness cost that contributes to their clinical advantage. |
| 27 | EVIDENCE OF A PROTECTIVE ROLE FOR CYTOKINE/CHEMOKINE PRODUCTION IN HIV INFECTION Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 27) Joseph Casazza1, J Brenchley1, R Ayana1, M Roederer1, D Douek1, M Betts2, and R Koup1 These data show a marked difference in cytokine/chemokine production and surface mobilization of CD107a between pp65-specific and gag-specific CD4+ T cells. In addition, our data show that MIP1-β-producing pp65-specific CD4+ T cells consistently showed a lower level of cell-associated Gag DNA than MIP1-β-non-producing pp65-specific CD4+ T cells. These data suggest an explanation for the persistence of CMV-specific CD4+ T cells in patients with AIDS. |
| 28 | SUBSTANTIAL CD4+ T-CELL RECOVERY AND RECONSTITUTION OF TISSUE ARCHITECTURE IN GUT-ASSOCIATED LYMPHOID TISSUE IN ADVANCED HIV-1 INFECTION FOLLOWING INITIATION OF HAART Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 28) E Connick1, Derek Shenefelt1,2, J Folkvord1, M Thrun3, S MaWhinney1, J Gathe4, S Lundy5, and S Becker6 NVP/TZV in advanced HIV-1 infection results in substantial recovery of CD4+ T cells and reconstitution of tissue architecture in GALT. Increases in CD4+ T cells are significantly larger in GALT than peripheral blood, particularly during the first 24 weeks of therapy. |
| Session 11—Oral Abstracts Issues in Prevention of HIV Transmission and ART |
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| 29 | PRE-EXPOSURE PROPHYLAXIS IN MACAQUES AGAINST RECTAL SIV CHALLENGE BY MUCOSALLY APPLIED PMPA: POTENTIAL FOR COMPLEMENTATION OF MICROBICIDE AND VACCINATION STRATEGIES Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 29) Martin Cranage1, S Sharpe2, A Cope1, C Herrera1, M Dennis2, N Berry3, C Ham3, P Anton4, I McGowan4, and R Shattock1 These data indicate that rectal pre-dosing with TDF gel has potential as part of a microbicide strategy and may enable priming of the immune system through mucosal exposure to virus challenge. |
| 30 | THE EFFECT OF SUPPRESSIVE ACYCLOVIR THERAPY ON HIV CERVICOVAGINAL SHEDDING IN HIV- AND HSV-2-INFECTED WOMEN, CHIANG RAI, THAILAND Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 30) Eileen Dunne1, S Whitehead1,2, M Sternberg1, S Thep-Amnuay2, W Leelawiwat2, J McNicholl1,2, S Sumanapun3, J Tappero1,2, T Siriprapasiri4, and L Markowitz1 Most women co-infected with HIV and HSV-2 had detectable HIV genital shedding at baseline. There was a significant difference in CVL HIV between the 2 treatment groups, suggesting a treatment effect. The study will be unblinded when all primary analyses are complete. |
| 31 | CHLAMYDIAL AND GONOCOCCAL INFECTION AMONG GAY AND BISEXUAL MEN AT THE TIME OF HIV+ TEST RESULT: IMPLICATIONS FOR CO-TREATMENT, SAN FRANCISCO, 2004-2006 Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 31) Katherine Scott, C Kent, K Ahrens, S Philip, and J Klausner The high prevalence of chlamydia and gonorrhea, regardless of HIV status, highlights the importance of screening for both infections at all exposed anatomic sites. Furthermore, the substantial prevalence of chlamydia and gonorrhea among newly identified HIV+ gay men at our STD clinic is similar to prevalence estimates of chlamydia in gonorrhea-infected patients, where presumptive treatment is recommended. Rapid HIV testing is becoming widely available at STD clinics in the United States. Presumptive same-day chlamydia and gonorrhea treatment among gay men with newly identified HIV infection should be studied to limit the further transmission of both STD and HIV. |
| 32 | POTENTIAL EFFECT OF ANTIRETROVIRAL CHEMOPROPHYLAXIS ON HIV-1 TRANSMISSION IN RESOURCE-LIMITED SETTINGS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 32) Ume Abbas1, R Anderson2, and J Mellors1 PrEP is predicted by complex modeling to have significant public health benefit. This benefit can be lost, however, by sexual disinhibition of the population on PrEP or a high PrEP discontinuation rate, especially with marginal efficacy of PrEP (≤50% or less). |
| 33 | EFAVIRENZ- VS NEVIRAPINE-BASED ART REGIMENS: ADHERENCE AND VIROLOGIC OUTCOMES Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 33) Jean Nachega1, M Hislop2, D Dowdy1, L Regensberg2, R Chaisson1, and G Maartens3 Use of EFV led to faster viral suppression and slower viral rebound than NFV in this South African population, and was associated with better adherence. The mechanism for these findings deserves further exploration. |
| 34 | DETERMINANTS OF MORTALITY AMONG HIV-INFECTED INDIVIDUALS RECEIVING HOME-BASED ART IN RURAL UGANDA Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 34) David Moore1,2, C Yiannoutsos3, B Musick3, R Downing1, W Were1, R Degerman1, L Alexander1, and J Mermin1 Strongly associated with mortality while receiving ART are conditions that can be remedied—such as low body mass index and anemia—or prevented—such as TB, candidiasis, and cryptococcal disease. These conditions should be addressed through interventions, such as food supplementation, aggressive treatment of anemia, and specific preventive therapy. Adherence to therapy assumes greater importance with increasing time on ART. |
| 35 | OUTCOMES OF ADULTS RECEIVING SECOND-LINE ART IN MÉDECINS SANS FRONTIÈRES-SUPPORTED PROJECTS IN RESOURCES-LIMITED COUNTRIES Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 35) M Pujades1, Alexandra Calmy2, D O'Brien3, P Humblet4, and MSF HIV/AIDS working group Adult patients on ART in MSF-supported programs in resource-limited countries have infrequently required change to second-line regimens. Early outcomes for adults on protease inhibitor (PI) -based second-line ART regimens appear to be satisfactory. |
| 36LB | EFFICACY OF KALETRA-BASED SECOND-LINE ART IN CAMBODIA Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 36LB) Laurent Ferradini1, O Segeral2, J Nouhin3, S Leakhena1, O Vara2, A Dulioust2, E Nerrienet3, J F Delfraissy4, and the ARV Second Line Study Group of Cambodia These first data in Cambodia outline the efficacy of Kaletra-based second-line ART in resource-limited settings and show the large extend of the immune reconstitution. They also reveal the short-term efficacy of empiric Kaletra-based second line given without virological examination. Second line antiretroviral molecules are urgently and widely needed at affordable prices in resource-limited countries. |
| Session 12—Oral Abstracts Metabolic and Cardiovascular Complications of ART |
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| 37 | HIV-RELATED IMMUNE SUPPRESSION AFTER ART PREDICTS RISK OF NON-OPPORTUNISTIC DISEASES: RESULTS FROM THE FIRST STUDY Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 37) Jason Baker1,2, G Peng1, J Rapkin1, D Abrams3, M Silverberg4, W Cavert1, R MacArthur5, W Henry1,2, J Neaton1, and Terry Beirn Community Prgms for Clin Res on AIDS (CPCRA) Higher, latest CD4 count was associated with a reduced risk of non-OD events (liver, CV, renal, and cancer), though to a lesser degree than with OD events. These data suggest that treatment strategies minimizing the time spent at lower CD4 counts will prevent both non-OD and OD events. |
| 38 | METABOLIC OUTCOMES OF ACTG 5142: A PROSPECTIVE, RANDOMIZED, PHASE III TRIAL OF NRTI-, PI-, AND NNRTI-SPARING REGIMENS FOR INITIAL TREATMENT OF HIV-1 INFECTION Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 38) Richard H. Haubrich1, S Riddler2, G DiRienzo3, L Komarow3, W Powderly4, K Garren5, T George6, J Rooney7, J Mellors2, D Havlir8, and the AIDS Clinical Trials Group 5142 Study Team A NRTI-sparing regimen (LPV+EFV) increased lipids significantly more than EFV or LPV+2 NRTI regimens. Triglyceride increases were also greater in LPV compared to EFV+NRTI regimens, but cholesterol changes were not significantly different. Compared to EFV, LPV had less lipoatrophy when given with NRTI. The frequency of lipoatrophy was lowest in NRTI-sparing and TDF-containing regimens. |
| 39 | EZETIMIBE’S EFFECTS ON THE LDL CHOLESTEROL LEVELS OF HIV-INFECTED PATIENTS RECEIVING HAART Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 39) David Wohl1, P Hsue2, S Richard1, A Schnell2, S Napravnik1, R Simpson1, J Keys1, and D Waters2 Ezetimibe alone led to significant and clinically meaningful declines in LDL-C and was well-tolerated. This trial, the first placebo-controlled study of ezetimibe in HIV+ patients, suggests a role for ezetimibe in the management of elevated LDL-C in patients with HIV. Further, for patients unable to take a statin, monotherapy with ezetimibe may be an option. |
| 40 | POLY-L-LACTIC ACID INJECTIONS FOR FACIAL LIPOATROPHY: A RANDOMIZED, MULTICENTER TRIAL Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 40) Dianne Carey1, D Baker2, N Easey3, K Petoumenos1, S Emery1, J Chuah4, K Machon5, G Rogers6, D Cooper1,3, D Cooper1,3, A Carr3, and for the Facial Lipoatrophy Study in HIV (FLASH) Investigators Although 4 facial injections of poly-L-lactic acid over 6 weeks in HIV-infected adults with facial lipoatrophy did not increase facial soft tissue volume overall, but prevented deterioration in injected areas. Poly-L-lactic acid injections were administered safely and were well tolerated. Objectively assessed relative increases in cheek subcutaneous thickness were less than reported in other studies. |
| 41 | INTERRUPTION OF ART AND RISK OF CARDIOVASCULAR DISEASE: FINDINGS FROM SMART Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 41) Andrew Phillips1, A Carr2, J Neuhaus1, F Visnegarwala3, R Prineas4, W Burman5, I Williams6, F Drummond7, D Duprez1, J Lundgren8, and others for the SMART Study Group A borderline significant excess risk of CVD was observed in DC compared to VS patients in SMART. There was no evidence that interruption immediately increases risk of CVD, but longer-term consequences cannot be excluded. On balance, lipid changes were unfavorable after interruption in DC patients, and the extent of this differed according to baseline ART regimen. |
| 42 | ALENDRONATE WITH CALCIUM AND VITAMIN D SUPPLEMENTATION IS SUPERIOR TO CALCIUM AND VITAMIN D ALONE IN THE MANAGEMENT OF DECREASED BONE MINERAL DENSITY IN HIV-INFECTED PATIENTS: RESULTS OF ACTG 5163 Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 42) Grace A McComsey1, M Kendall2, P Tebas3, S Swindells4, E Hogg5, B Alston-Smith6, C Suckow7, G Gopalakrishnan8, C Benson9, D Wohl10, and AIDS Clinical Trials Group ACTG 5163 The results demonstrate that once-weekly alendronate is safe and efficacious in the treatment of decreased bone mineral density in HIV-infected patients. Vitamin D and calcium alone is associated with modest improvements in bone mineral density. |
| 43 | EFFECTS OF A NRTI, STAVUDINE, ON INSULIN SENSITIVITY AND MITOCHONDRIAL FUNCTION IN MUSCLE OF HEALTHY ADULTS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 43) A Fleischman1, S Johnsen1,2, D Systrom1, M Hrovat1, C Farrar1, W Frontera1,3, K Fitch1, M Torriani1, H Cote4, and Steven Grinspoon1 This is the first study to demonstrate that d4T causes alterations in muscle mitochondrial content and insulin sensitivity in healthy individuals. The current study supports the hypothesis that alterations in mitochondrial function in muscle contribute to the development of insulin resistance in non HIV-infected patients and also demonstrates an important mechanism of toxicity in HIV-infected patients. |
| 44 | SIGNIFICANT SPARING OF PERIPHERAL LIPOATROPHY BY HIV TREATMENT WITH LPV/R + ZDV/3TC INDUCTION FOLLOWED BY LPV/R MONOTHERAPY COMPARED WITH EFV + ZDV/3TC Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 44) DW Cameron1, B da Silva2, J Arribas3, F Pulido4, H Katner5, K Wikstrom2, M Woulfe2, K Niemi2, M King2, and G Hanna2 Treatment with LPV/r monotherapy (compared with EFV+ZDV/3TC) was significantly and independently associated with sparing of peripheral lipoatrophy. |
| 45 | EFFECTS OF TH9507, A GROWTH HORMONE RELEASING FACTOR ANALOG, ON HIV-ASSOCIATED ABDOMINAL FAT ACCUMULATION: A MULTICENTER, DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL WITH 412 RANDOMIZED PATIENTS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 45) J Falutz1, S Allas2, K Blot2, D Kotler3, M Somero4, D Berger5, S Brown6, G Richmond7, J Fessel8, and Steven Grinspoon9 These data indicate that daily administration of 2 mg TH9507 for 26 weeks preferentially decreased VAT and improved lipid profile. TH9507 was well tolerated and may represent a novel treatment strategy for HIV patients with central fat accumulation, including those with impaired glucose homeostasis. |
| Session 17—Symposium Molecular Co-Factors in HIV Infection |
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| 47 | TIP47, A CELLULAR CO-FACTOR INVOLVED IN HIV-1 ENVELOPE INCORPORATION INTO VIRIONS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 47) Clarisse Berlioz-Torrent In conclusion, we have identified TIP47 as a cellular co-factor involved in the incorporation of full-length HIV-1 Env into HIV-1 Gag particles. This function involves the interaction between TIP47 and 2 essential viral proteins, Gag and Env, making TIP47 indispensable for HIV-1 Env incorporation and HIV-1 infectivity. |
| 48 | REGULATION OF HIV-1 NUCLEAR ENTRY Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 48) Vineet KewalRamani1, Z Ambrose1, T Martin1, K Lee1, N Vandegraaff2, A Mulky1, J Coffin3, A Engelman2, S Hughes1, and D Unutmaz4 We hypothesize that the different mutations influence CA dissociation from the HIV-1 reverse transcription complex (RTC), and that truncated CPSF6 interferes with cellular factors that aid in this dissociation. In such a model, nuclear entry by HIV-1 is regulated via CA dissociation from the RTC, which itself is dependent on cell factors targeted by truncated CPSF6. |
| 49 | FUNCTIONS OF APOBEC3 COMPLEXES AND P BODIES Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 49) Tariq Rana Our recent findings showing that APOBEC3G localizes to specialized compartments in the cytoplasm of mammalian cells known as mRNA processing (P) bodies, which function in the degradation and storage of cellular mRNA, will be presented. Implications for APOBEC3G function and for the role of P-bodies in both cellular defense against viruses and retroviral assembly will be discussed. |
| Session 18—Oral Abstracts Novel Approaches for Pharmacokinetic Assessment |
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| 50 | PHENOTYPING FOR DRUG INTERACTIONS: COCKTAILS ANYONE? Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 50) Angela Kashuba This overview will review current probes and cocktails for assessing drug-metabolizing enzyme and transporter activity, discuss their value in understanding and predicting antiretroviral drug interactions, and examine their application to patient care. |
| 51 | CONCENTRATIONS OF LOPINAVIR AND RITONAVIR IN HAIR ARE STRONGLY CORRELATED WITH VIROLOGIC SUCCESS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 51) Monica Gandhi1, N Ameli1, P Bacchetti1, Y Huang1, K Anastos2, M Cohen3, S Gange4, A Levine5, C Hyman6, R Greenblatt1, and Women's Interagency HIV Study (WIHS) In models examining predictors for virologic success after initiating LPV/RTV-based regimens, hair levels of LPV or RTV at 6 months were each strong, independent predictors of virologic success, even when controlled for self-reported adherence, pre-treatment viral load, and prior ART experience. Levels of ART in small samples of hair estimate long-term exposure to a drug and may serve as noninvasive monitoring tools for treatment outcomes. |
| 52LB | BIOEQUIVALENCE OF PILOT TABLET FORMULATIONS OF RITONAVIR TO THE MARKETED SOFT GEL CAPSULE AT A DOSE OF 100 MG Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 52LB) Y Cai1, C Klein1, U Roggatz2, W Roth2, T Jung2, K Fastnacht2, J Morris1, B Freyer-Kern2, B Bernstein1, and George Hanna1 RTV prototype tablet formulations A and B met bioequivalence criteria with respect to RTV Cmax, AUCt, and AUCinf and warrant further development. Long-term stability evaluations under a variety of temperature and humidity conditions and additional bioavailability studies are ongoing to guide selection of a formulation suitable for registration. |
| 53 | CELL-DEPENDENT COMPARTMENTALIZATION OF ZIDOVUDINE- AND LAMIVUDINE-TRIPHOSPHATE CONCENTRATIONS IN HIV-SERONEGATIVE ADULTS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 53) Peter L. Anderson, J H Zheng, J Gerber, C Fletcher, T King, and J Predhomme Compared with unfractionated PBMC, CD4-depleted PBMC had 1.3-fold higher ZDV-triphosphates and 1.4-fold higher 3TC-triphosphates in HIV-seronegative adults, which does not completely explain the magnitude of triphosphate differences seen in patients with depleted CD4 cells. An important finding was that ZDV-triphosphate concentrations were significantly decreased in CD4 purified cells. Triphosphate compartmentalization could lead to HIV sanctuary sites for cells with low triphosphates or toxicity for cells with high triphosphates. |
| Session 19—Symposium Drivers of the HIV Epidemic and Potential Interventions |
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| 54 | WHAT'S DRIVING THE EUROPEAN HIV EPIDEMIC? Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 54) Anne Johnson This paper reviews the socioeconomic, behavioral, and biological factors that contribute to the diversity and to the current epidemic trends. It will also review demographic, behavioral, and biological influences and their relative contribution to the continuing spread of HIV. |
| 56 | THE STD-HIV CONNECTION FROM RESEARCH TO ACTION: ARE WE LOST IN TRANSLATION? Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 56) Judy Wasserheit How should HIV prevention programs around the world allocate finite resources in the context of the available RCT data, which are currently limited to the results of trials conducted using antimicrobials for curable STD, but not for HSV-2, the most common etiology of genital ulcer disease, particularly in generalized HIV epidemics? The 3 inter-related concepts of epidemic phase, incidence : prevalence ratios, and acute HIV infection will be explored together with data from the trials and selected ecological studies to propose approaches to translate these divergent trial results into effective prevention programs and policies. |
| 57 | NEW HIV PREVENTION TECHNOLOGIES: WHAT IF THEY WORK? Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 57) Ward Cates, Jr This presentation will synthesize the evidence on our currently available HIV prevention methods, summarize the ongoing trials and their anticipated timetable for results, and portray the potential impact if any of these HIV prevention methods are shown to be effective. What if any of these ongoing trials are successful? At least 5 dimensions of research translation will need to be considered: the level of evidence required for regulatory approval, the impact at both the individual- and population-level, the role of adherence in determining the public health effectiveness of each approach, translation of the definitive research results into real world practice, and the impact of new technologies on the conduct of future HIV prevention trials. Scientists and policy makers must anticipate these multiple dimensions of trial “success” if hopes for future HIV prevention are to be realized. |
| Session 20—Symposium The Latest Concepts in HIV Drug Resistance |
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| 58 | RTI MECHANISMS OF RESISTANCE AND INTERACTIONS THAT IMPACT RESPONSE Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 58) Nicolas Sluis-Cremer By understanding the mechanisms of RTI resistance and the interactions between resistance mutations, appropriate RTI drug combinations can be formulated that provide sustained clinical benefit. |
| 59 | IMPACT OF SUBTYPE ON HIV DRUG RESISTANCE Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 59) Jonathan Schapiro Pooling data in large collaborative efforts will facilitate further progress. In addition, continued investigation into the complex relationships between genetic diversity, specific drug susceptibility and viral replication will provide important insight. |
| 60 | TRANSMISSION OF HIV DRUG RESISTANCE AND TREATMENT RESPONSE Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 60) Susan Little1, S Frost1, D Smith1, S May1, N Parkin2, D Richman1,3, and D Richman1,3 The prevalence of transmitted drug resistance in most surveillance studies and the long-term persistence of this drug resistance strongly support the routine use of HIV resistance genotyping for all newly HIV diagnosed subjects. |
| 61 | CLINICAL IMPLICATIONS OF LOW-FREQUENCY HIV-1 VARIANTS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 61) Jeffrey Johnson The findings from these studies imply that low-frequency treatment-relevant mutations persisting above naturally occurring levels in drug-naïve patients are associated with virologic failure and provide evidence that minority mutations can have clinical consequences. Additional sensitive testing is necessary to further evaluate the impact of minority proviral variants and of linked low-frequency mutations on antiretroviral responses. |
| Session 21—Plenary Outcomes of ART in Resource-Limited and Industrialized Countries |
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| 62 | OUTCOMES OF ART IN RESOURCE-LIMITED AND INDUSTRIALIZED COUNTRIES Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 62) Matthias Egger This presentation will describe and compare relevant outcomes of ART in resource-limited and industrialized settings, and discuss pertinent issues, including, for example, the cost of starting treatment late. |
| Session 22—Plenary Status of the US HIV/AIDS Epidemic: Is It Changing and If Not, Why Not? |
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| 63 | STATUS OF THE US HIV/AIDS EPIDEMIC: IS IT CHANGING AND IF NOT, WHY NOT? Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 63) Harold Jaffe Funding priorities for HIV prevention must include implementing what works and evaluating what might work. Prevention leadership in MSM and African American communities is needed to confront the enormous disparities of the epidemic. To be realistic about what can be done, the limits of public health in changing human behaviour must also be acknowledged. |
| Session 23—Oral Abstracts Pathogenesis of Acute and Chronic Infection |
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| 64 | ENDOGENOUS RETROVIRUSES OF MAMMALIAN GENOMES: MOLECULAR BIOLOGY AND ROLES IN PHYSIOLOGY AND PHYSIOPATHOLOGY Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 64) Thierry Heidmann Although most ERV are defective, due to genetic drift, the molecular biology of functional elements that could be identified in the human and murine genomes will be presented. Overall lessons that ERV teach us on the pathological mechanisms of infectious retroviruses—and vice versa—will be discussed. |
| 65 | MICROBIAL TRANSLOCATION IS A CAUSE OF SYSTEMIC IMMUNE ACTIVATION IN CHRONIC HIV INFECTION Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 65) Jason Brenchley1, D Price1, T Schacker2, G Silvestri3, O Lambotte4, A Landay5, L Picker6, M Lederman7, S Deeks8, and D Douek1 These studies strongly suggest that translocation of microbial products from a damaged gastrointestinal tract is an important cause of immune activation in chronic HIV disease. Moreover, these data provide novel directions for therapeutic interventions that modify the consequences of HIV infection. The aim would be to prevent or reduce the propagation of HIV at mucosal surfaces, to restore the immunological and epithelial integrity of the mucosal barrier, and to block pathways through which microbial products cause systemic immune activation. |
| 66 | PD-1hi SIV-SPECIFIC CD8+ T CELLS EXPRESS MULTIPLE EFFECTOR FUNCTION AND HAVE LOW PROLIFERATIVE CAPACITY AND HIGH SENSITIVITY TO ACTIVATION-INDUCED CELL DEATH Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 66) Consatntinos Petrovas1, D Price1, J Mattapallil1, C Geldmacher1, V Cecchinato2, D Ambrozak1, M Roederer1, D Douek1, G Franchini2, and R Koup1 Our data point to a negative role for PD-1 in SIV-specific CD8+ T-cell function. Manipulation of the interaction of PD-1 with its ligands could potentially benefit the restoration of cytotoxic T lymphocyte (CTL) responses in SIV infection, probably by affecting their survival ability. |
| 67 | CD4 RECONSTITUTION OF LYMPHOID TISSUES IS DEPENDENT ON EARLIER INITIATION OF HAART Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 67) J Estes1, J Brenchley2, J Bathold1, A Khoruts1, G Beilman1, J Baker1, C Reilly1, D Douek2, A Haase1, and Timothy Schacker1 Lymphatic tissues do not uniformly reconstitute CD4+ T cells with HAART. Lymph node and Peyers patches are capable of limited reconstitution, the degree of which depends on earlier initiation of HAART than is currently recommended. This was most striking for central memory CD4 cells in Peyers patches. |
| 68 | HIV-1 SUBTYPE D INFECTION IS ASSOCIATED WITH FASTER DISEASE PROGRESSION THAN SUBTYPE A, IN SPITE OF SIMILAR HIV-1 PLASMA VIRAL LOADS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no.68) Jared Baeten1, B Chohan1, L Lavreys1, V Chohan2, R McClelland1,2, L Certain1, K Mandaliya3, W Jaoko2, and J Overbaugh4 Among this cohort of Kenyan women followed from the time of HIV-1 acquisition, infection with HIV-1 subtype D was associated with a faster rate of CD4 decline and a >2-fold higher risk of death than with subtype A infection, in spite of similar HIV-1 plasma viral loads. |
| 69 | MUCOSAL CD4+ T-CELL DEPLETION AND TRANSIENT IMMUNE ACTIVATION DURING THE EARLY PHASE OF NON-PATHOGENIC SIV INFECTION OF SOOTY MANGABEYS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 69) Shari Gordon1, S Bosinger2, J Brenchley3, C Apetrei4, I Pandrea4, D Kelvin5, S Staprans1, D Douek3, D Sodora6, and G Silvestri1,7 These data indicate that non-pathogenic SIV infection of sooty mangabeys is similar to pathogenic HIV/SIV infections in terms of the pattern of target cell depletion, as it is associated with an early and severe loss of CD4+ T cells in mucosal tissues. However, the lack of sustained immune activation and maintenance of mucosal immune function in the presence of fewer CD4+ T cells may protect SIV-infected sooty mangabeys from systemic CD4+ T cell depletion and progression to AIDS. |
| 70 | PD-1 EXPRESSION ON HIV-SPECIFIC CD4+ T CELLS IS DRIVEN BY HIV REPLICATION AND IS ASSOCIATED WITH T-CELL DYSFUNCTION Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 70) M D'Souza, A Fontenot, D Mack, S Dillon, A Meditz, C Wilson, E Connick, and Brent Palmer These data indicate that PD-1 expression on HIV-specific CD4+ T cells is driven by HIV replication. These findings also demonstrate that the PD-1 pathway is active in both the peripheral blood and especially the lymph node during chronic HIV infection, and that it provides a potential target for enhancing the ability of HIV-specific CD4+ T cells to control disease. |
| 71LB | CO-RECEPTOR SWITCH IN A MACAQUE INFECTED WITH CCR5 (R5)-TROPIC SIMIAN-HUMAN IMMUNODEFICIENCY VIRUS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no.71LB) Siu-hong Ho1, L Shek1, A Li1, S Tasca1, A Gettie1, J Blanchard2, D Boden1, and C Cheng-Mayer1 We report here the first case of X4 virus evolution in a R5 SHIV-infected rhesus macaques, demonstrating that co-receptor switch can happen in a non-human primate model of HIV/AIDS. Co-receptor switch in macaques appears to require a process of multiple mutation accumulation, and is associated with envelope sequence changes similar to those reported in humans, suggesting that the R5 to X4 evolution pathways in the 2 hosts overlap. The finding of X4 emergence in a macaque with low virus-specific immune responses lends support to a role for antiviral immunity in suppressing HIV-1 co-receptor switch. |
| Session 24—Oral Abstracts Perinatal Transmission and Therapy of Pediatric HIV Infection: Challenges and Complications |
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| 72 | PLASMA ANTIRETROVIRAL CONCENTRATIONS IN BREASTFEEDING INFANTS WHOSE MOTHERS ARE RECEIVING HAART Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 72) Mark Mirochnick1, T Thomas2, E Capparelli3, C Zeh2, D Holland3, R Masaba4, P Odhiambo4, M Fowler5, P Weidle6, and M Thigpen6 Infant drug exposure from breast milk will be determined by the magnitude of breast milk drug delivery and by infant drug absorption, distribution, and elimination. For ZDV, maternal plasma and breast milk concentrations were low and infant concentrations nearly always below the quantitation limit, consistent with a short plasma half-life in both mother and infant. 3TC was concentrated in breast milk and has a longer plasma half-life than ZDV; median infant 3TC concentrations exceeded the mean 3TC trough concentrations of 40 ng/mL seen in adults with once-daily dosing. NVP breast milk concentrations were slightly below those in maternal plasma. NVP plasma half-life is long, and in some infants NVP concentration exceeded the target concentrations of 3400 ng/mL used in therapeutic drug monitoring programs. These nursing infants whose mothers were receiving HAART demonstrated low ZDV concentrations but 3TC and NVP concentrations of sufficient magnitude to have potential biologic effects such as drug toxicity or, in those infants that do become HIV-infected, partial suppression of HIV replication or development of drug resistance. |
| 73 | POSTNATAL TRANSMISSION OF HIV AND BREAST MILK VIRAL LOAD AND SODIUM LEVEL DURING THE FIRST 4 MONTHS OF BREASTFEEDING Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 73) Katherine Semrau1, M Ghosh2, C Kankasa3, M Sinkala4, P Kasonde3, M Mwiya3, D Thea1, L Kuhn5, and G Aldrovandi2 Consistent viral shedding and high breast milk viral load are strong predictors of MTCT. While increased sodium concentrations later in breastfeeding correlate with breast milk viral load and maternal HIV indicators and are predictive of HIV transmission, increased breast milk Na appears to be normal in early lactation and is not predictive of MTCT. |
| 74 | PERINATAL TRANSMISSION AND THERAPY OF PEDIATRIC HIV INFECTION: CHALLENGES AND COMPLICATIONS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 74) Moses Sinkala1, L Kuhn2, C Kankasa3, P Kasonde3, C Vwalika1, M Mwiya3, N Scott4, K Semrau4, G Aldrovandi5, D Thea4, and Zambia Exclusive Breastfeeding Study Group (ZEBS) Our results caution against early cessation of breastfeeding for HIV-infected women living in low-resource settings. In our study, stopping breastfeeding at 4 months resulted in less than anticipated reduction of HIV transmission, a benefit that was offset by increased mortality among uninfected infants. For HIV-infected infants, there was also a substantial mortality risk associated with stopping breastfeeding early. Programs providing HIV diagnosis services should strongly encourage breastfeeding into the 2nd year of life for infants found to be HIV-infected. |
| 75 | MATERNAL HSV-2 CERVICOVAGINAL SHEDDING INCREASES THE RISK OF INTRA-PARTUM HIV-1 TRANSMISSION Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 75) Sara Whitehead1,2, L Bollen1, W Leelawiwat1, P Mock1, S Asavapiriyanont3, A Chalermchokecharoenkit4, N Vanprapar4, T Chotpitayasunondh3, N Shaffer2, and R Chuachoowong1 Our data show for the first time that perinatal CVL HSV-2 shedding is associated with increased risk of intra-partum HIV transmission, and that the effect on transmission was independent of CVL and plasma HIV viral load. These findings suggest that interventions to control HSV-2 shedding could further decrease intra-partum HIV transmission. |
| 76 | ALTERATION OF CIRCULATING OSTEOIMMUNE FACTORS MAY BE RESPONSIBLE FOR BONE METABOLISM DERANGEMENT IN HIV-INFECTED CHILDREN AND ADOLESCENTS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 76) S Mora1, V Giacomet2, I Zamproni1, L Cafarelli2, G Pattarino2, D Frasca2, G Zuccotti2, and Alessandra Viganò2 The current data confirm the presence of an altered bone metabolism in HIV-infected children and adolescents. The high bone resorption rate seems to be the result of a profound modification of the factors regulating osteoclastogenesis, since the ratio between OPG and RANKL was in favor of the latter. Moreover, in vitro evidence indicates a role of HIV infection and antiviral treatment in the production of RANKL by T cells. Our patients were all on long-term HAART, and thus the high concentration of RANKL observed may be in part due to the use of antiviral drugs. |
| 77 | PLASMA CONCENTRATIONS OF EFAVIRENZ AND LOPINAVIR IN CHILDREN WITH AND WITHOUT RIFAMPICIN-BASED ANTI-TB TREATMENT Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 77) Yuan Ren1, J Nuttall1, C Egbers2, B Eley1, T Meyers2, G Maartens1, P Smith1, and H McIlleron1 Rifampicin did not significantly reduce EFV concentrations. That 50% of children had EFV Cmin below the minimum recommended concentration raises concern that a substantial proportion may be at risk of the rapid emergence of EFV-resistant mutations and treatment failure. This suggests that EFV doses should be re-evaluated, especially because therapeutic drug monitoring is seldom available in developing countries. LPV Cmin was similar between the 2 groups. In all 28 children, LPV Cmin was above the minimum therapeutic level (1 mg/L). This study confirmed that additional RTV can be used to retard LPV elimination, thus overcoming the reduction of LPV levels caused by rifampicin. |
| 78 | THE EFFECT OF COTRIMOXAZOLE PROPHYLAXIS AND INSECTICIDE-TREATED BEDNETS ON THE RISK OF MALARIA AMONG HIV-INFECTED UGANDAN CHILDREN Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 78) Anne Gasasira1, M Kamya1, J Achan1, T Mebrahtu2, T Ruel2, A Kekitiinwa3, E Charlebois2, P Rosenthal2, D Havlir2, and G Dorsey2 In a malaria-endemic area with high-level antifolate resistance, CTX prophylaxis and insecticide-treated bed-nets were associated with dramatic reductions in malaria among HIV-infected children compared to healthy controls. Fevers among HIV-infected children receiving CTX and insecticide-treated bed-nets are unlikely due to malaria, and other etiologies should be sought. |
| 79 | CATALYZING THE CARE AND TREATMENT OF HIV-INFECTED CHILDREN IN SUB-SAHARAN AFRICA: EARLY OUTCOMES FROM 5 BAYLOR COLLEGE OF MEDICINE CENTERS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 79) Mark Kline, G Anabwani, A Kekitiinwa, E Mohapi, B Bhembe, P Kazembe, N Calles, M Mizwa, D Jones, M Ferris, and Baylor Coll of Med Intl Pediatric AIDS Initiative State-of-the-art HIV/AIDS care and treatment can be administered to large numbers of children in resource-poor African settings with rates of success comparable to those observed in the United States. |
| Session 25—Oral Abstracts OIs, AIDS-Defining Conditions, and HIV-1 Disease Burden |
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| 80 | CLINICAL ENDPOINTS FOR RANDOMIZED CLINICAL TRIALS: ALL AIDS-DEFINING CONDITIONS ARE NOT CREATED EQUAL Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 80) Amanda Mocroft and Antiretroviral Therapy Cohort Collaboration The ADC used to define AIDS were historically identified to track an emerging epidemic and were not intended for use as a clinical staging system, yet they are frequently used for this purpose. In the cART era, mortality rates following an ADC depended strongly on the ADC diagnosed, although it was not possible to determine whether patients died from the ADC they contracted. The ranking of severity of ADC would be useful in design of clinical endpoint trials and for patient management. |
| 81 | EARLY MORTALITY AMONG PATIENTS WITH HIV-ASSOCIATED TB IN AFRICA: IMPLICATIONS FOR THE TIME TO INITIATE ART Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 81) Stephen Lawn1,2, L Myer3,4, L G Bekker1, and R Wood1 Advanced immunodeficiency accounts for the extremely high early mortality risk among patients with TB accessing ART in this setting. Pending the results of randomised controlled trials, these data strongly support a policy of initiation of ART within the first month from TB diagnosis among patients with CD4 cell counts <100 cells/µL or AIDS. |
| 82 | CAUSES OF DEATH IN HIV-INFECTED ADULTS WITH TB ADMITTED TO 2 HOSPITALS IN SOWETO, SOUTH AFRICA Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 82) Neil Martinson1,2, M Hale2,3, A Karstaedt2,4, F Venter2, P King2,3, E Marais2,3, and R Chaisson1 Extensive pulmonary TB with dissemination and multiple HIV-associated pathologies were found, signifying that earlier diagnosis of both HIV and TB is urgently needed. Severe bacterial infections were the leading co-morbidity suggesting that hospitalized, HIV-infected adults with TB may benefit from potent, broad-spectrum antibiotics. |
| 83 | COTRIMOXAZOLE PROPHYLAXIS REDUCED THE EARLY MORTALITY OF HIV-INFECTED PATIENTS ON ART IN MALAWI Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 83) David Lowrance1, S Makombe2, A Harries2,3,4, J Yu5, J Aberle-Grasse6, O Eiger6, R Shiraishi1, B Marston1, T Ellerbrock1, and E Libamba2 CTX prophylaxis was associated with a mortality reduction of 41% during the first 6 months of ART in patients in Malawi. In this and other resource-limited settings, CTX prophylaxis could significantly improve the survival of patients on ART because CTX is readily available, comparatively cheap, and has a major impact on mortality during the first 6 months of ART. |
| 84 | HIV-INDUCED IMMUNODEFICIENCY AND RISK OF FATAL AIDS-DEFINING AND NON-AIDS-DEFINING MALIGNANCIES: RESULTS FROM THE D:A:D STUDY Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 84) Antonella D'Arminio Monforte1, D Abrams2, C Pradier3, R Weber4, F Bonnet5, S De Wit6, N Friis-Møller7, A Phillips8, C Sabin8, J Lundgren7, and The D:A:D Study Group Fatal nADM are now more common than fatal ADM in contemporary populations with access to ART, and the incidence of fatal nADM will likely continue to increase as the HIV-infected population ages. Levels of HIV RNA did not influence risk of fatality from either type of malignancy, whereas immunodeficiency markedly increased risk of dying from both types of malignancies. Hence, prevention of development of advanced immunodeficiency and continued focus on reducing known risk factors (including smoking cessation and treatment of chronic hepatitis B virus infection) appear to be key strategies to prevent fatalities caused by malignancies in HIV-infected populations. |
| 85 | THE ESTIMATED BURDEN OF HIV DISEASE IN UGANDA, 2005-2010 Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 85) Wolfgang Hladik1, J Musinguzi2, W Kirungi2, A Opio2, J Stover3, F Kaharuza1, R Bunnell1, J Kafuko4, and J Mermin1 HIV/AIDS continues to be a leading cause of adult disease and death in Uganda. Prevention and treatment programs have a substantial effect on the burden of HIV/AIDS and, if scaled up, have potential to further mitigate it. |
| 86 | HIV TESTING FOR FAMILY MEMBERS OF HOSPITALIZED PATIENTS IN UGANDA Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 86) Happy Walusaga1, R Wanyenze1, C Nawavvu1, B mayanja1, J Ssenkusu1, J Ssempiira1, A Namale2, and M Kamya1 Routine offering of HIV testing to family members of patients identifies many additional HIV infections and discordant relationships. This innovative approach to increasing access to HIV prevention, care, and treatment for families merits expansion. |
| Session 26—Oral Abstracts New Antiretroviral Agents, Resistance Mechanisms, and Clinical Resistance |
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| 87 | NEXT GENERATION OF INHIBITORS OF HIV-1 INTEGRASE STRAND TRANSFER INHIBITOR: STRUCTURAL DIVERSITY AND RESISTANCE PROFILES Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 87) John Wai, T Fisher, M Embrey, M Egbertson, J Vacca, D Hazuda, M Miller, M Witmer, L Gabryelski, and T Lyle A potent integrase strand transfer inhibitor, MK-2048, with the potential to inhibit HIV-1 resistant variants generated with first generation compounds and good pharmacokinetic profiles in preclinical species was identified. |
| 88 | STRUCTURES OF HIV-1 REVERSE TRANSCRIPTASE COMPLEXED WITH NNRTI TMC278: CONFORMATIONAL AND POSITIONAL ADAPTABILITY OVERCOMES RESISTANCE MUTATIONS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 88) Joe D. Bauman1, K Das1, M Baweja1, A Clark Jr1, P Boyer2, A Shatkin1, P Lewi3, S Hughes2, and E Arnold1 The swiftness of crystallization of engineered RT that brought success in obtaining high-resolution structures of RT provides an excellent opportunity for accurate understanding of inhibitor-protein interactions, and the effects of resistance mutations. It also offers the opportunity to peruse systematic structure-based design of new RT inhibitors, and structure-based screening for new lead compounds directed to existing and possible new targets of RT. The technique of iterative crystal engineering can also be used in obtaining and improving crystals of important yet difficult proteins. |
| 89 | TERNARY COMPLEX FORMATION COMPROMISES THE INHIBITORY EFFECTS OF THE RT-ASSOCIATED RNase H INHIBITOR β-THUJAPLICINOL Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 89) Greg Beilhartz1, J Beutler2, S LeGrice2, and M Gotte1 Here we show mechanistic differences with regards to inhibition of the RT-associated RNase H activity in the context of binary and ternary complexes. Inhibition of RNase H cleavage is severely compromised with stable ternary complexes that freeze the substrate in the binding channel of RT, which is a possible factor that can compromise the antiviral effects of certain RNase H inhibitors. |
90 | 3’-AZIDO-3’-DIDEOXYTHIMIDINE SELECTS MUTATIONS IN THE CONNECTION (A371V) AND RNase H (Q509L) DOMAINS OF REVERSE TRANSCRIPTASE THAT INCREASE AZT RESISTANCE IN COMBINATION WITH THYMIDINE ANALOG MUTATIONS WITHOUT AFFECTING THE RATE OF AZT EXCISION ON A DNA/DNA TEMPLATE/PRIMER Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 90) Jessica Brehm, D Koontz, S Zelina, N Sluis-Cremer, and J Mellors The A371V and Q509L mutations are co-selected on the same genome as TAM and increase AZT resistance when combined with TAM. They also confer greater cross-resistance to 3TC, ABC, and TDF. A371V and Q509L do not affect the efficiency of ATP-mediated excision reactions carried out on DNA/DNA template/primer, but do affect the rate of DNA-dependent RNase H cleavage, suggesting a possible role for A371V/Q509L in AZT-MP excision from RNA/DNA template/primer. |
| 91 | SUPPRESSION OF DUAL-TROPIC HIV-1 VARIANTS BY THE CXCR4 INHIBITOR AMD3100 IS ASSOCIATED WITH EFFICIENCY OF CXCR4 USE AND CLONAL COMPOSITION OF THE BASELINE VIRUS POPULATION Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 91) Signe Fransen1, G Bridger2, J Whitcomb1, J Toma1, N Parkin1, C Petropoulos1, and W Huang1 This study indicates that AMD3100 has the ability to inhibit both X4-tropic and certain dual-tropic variants in vivo. Dual-tropic viruses exhibit considerable variation in their efficiency of CXCR4 and CCR5 co-receptor use. The efficiency of CXCR4 usage and the tropism composition of the baseline virus population appears to influence the suppression of dual-tropic variants by AMD3100. Further characterization of dual-tropic variants is needed to fully appreciate the susceptibility of dual tropic viruses to CXCR4 and CCR5 targeted therapies. |
| 92 | NEVIRAPINE-RESISTANT HIV-1 AMONG MOZAMBICAN INFANTS INFECTED IN UTERO VS INTRA-PARTUM OR EARLY POSTPARTUM Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 92) M Micek1,2, A Blanco1,2, E Matediane3, L Matunha2, I Beck4, S Dross4, P Montoya1,2, L Jamisse5, S Gloyd1,2, and Lisa Frenkel1 The selection of common NVP-resistance mutations was high in Mozambican infants receiving single-dose NVP and infected with HIV-1 in utero compared to infants infected intra-partum or early postpartum. While most mutants were detected through 8 weeks of age, the persistence and long-term consequences of these HIV-1 resistance mutations remains unknown. Further analyses in this study will focus on the persistence of mutants, as gauged by sensitive assays, in infants infected in utero versus intra-partum or early postpartum. |
| 93LB | SHORT-COURSE ZIDOVUDINE AND LAMIVUDINE OR SINGLE-DOSE NEVIRAPINE-CONTAINING PMTCT COMPROMISES 12-MONTH RESPONSE TO HAART IN AFRICAN WOMEN, ABIDJAN, CÔTE D’IVOIRE (2003-2006) Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 93LB) P Coffie1, D Ekouevi2, M L Chaix3, B Tonwe-Gold4, S Toure4, I Viho4, C Amani-Bosse4, V Leroy1, C Rouzioux3, François Dabis1, D Ekouevie1, and MTCT-Plus Initiative of ICAP Short course (ZDV±3TC) and sdNVP may induce viral resistance to NVP or 3TC that can impair the subsequent women’s response to HAART, an adverse phenomenon to be taken into account in PMTCT guidelines. |
| 94 | PREVALENCE OF HIV-1 DRUG RESISTANCE AFTER VIROLOGIC FAILURE OF FIRST HAART REGIMEN IN SOUTH AFRICA: INITIAL RESULTS OF THE SOUTH AFRICA RESISTANCE COHORT STUDY Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 94) Vincent C. Marconi1,2, H Sunpath3, Z Lu4, M Gordon5, K Koranteng6, J Hampton3, D Ross6, E Losina4, B Walker4, D Kuritzkes1, and SARCS Team Antiretroviral drug resistance has been detected in a growing number of South African patients with virologic failure of first-line ART. The resistance profiles predominantly contained nucleoside reverse transcriptase inhibitor (NRTI) and non-NRTI (NNRTI) mutations reflecting use of the first-line regimen. This study identified recent opportunistic infections as a major risk factor for virologic failure with drug resistance among HIV-1-infected South African patients with first-line ART failure. Further follow-up of this cohort is underway to determine the effectiveness of second-line regimens in this setting. |
| Session 31—Symposium T-Cell Based Vaccines: Promise of Clinical Efficacy? |
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| 95 | HOW CAN T-CELL-BASED VACCINES PROTECT AGAINST SIV AND HIV? Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 95) Mario Roederer These findings identify a key mechanism leading to differential rates of progression to AIDS in infected subjects. In addition, they point to the critical importance of reducing the cell-associated viral load during acute infection, through therapeutic or vaccination strategies. Finally, these studies show that a T-cell-based vaccine against HIV or SIV can have profound protective effects even in the absence of sterilizing immunity. |
| 96 | GLOBAL EPIDEMIOLOGY OF HIV: RISK FACTORS, SOCIAL NETWORKS, AND INTER-SUBTYPE RECOMBINANT STRAINS IN VACCINE TRIAL SITES Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 96) Francine McCutchan1, G Kijak1, S Tovanabutra1, E Sanders-Buell1, C Beyrer2, M deSouza3, M Arroyo3, M Robb1, D Birx1, and N Michael Michael1 Recombinant strains reflect the social networks in which they spread. In multiply exposed, high-risk groups, repeated cycles of dual infection and recombination leads to a dynamic network of complex and inter-related recombinants. CRF may emerge when strains from high-risk groups enter larger, but lower-risk, heterosexual networks, where lower dual infection rates lead to a stabilization of their structure. In vaccine trials, particularly those in high-risk groups, the possibility exists that vaccinees may be exposed to multiple HIV-1 strains in a single transmission event, and to related but non-identical recombinant strains in the population. |
| 97 | HOW CAN THE IMMUNOGENICITY OF pDNA VACCINES BE IMPROVED? Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 97) Michael Egan1, M Sidhu1, D Weiner2, G Pavlakis3, I Mathieson4, R Kjeken4, and J Eldridge1 Collectively, improved pDNA expression vectors, co-delivery of plasmid-based immunomodulators and improved DNA delivery bring the field closer to the design and development of an efficacious DNA vaccine for the prevention and treatment of HIV-1 infection. |
| 98 | STRATEGIES TO OVERCOME PRE-EXISTING VECTOR-SPECIFIC IMMUNITY Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 98) Dan Barouch These rare serotype and capsid chimeric rAd vectors could potentially serve as alternatives to rAd5 vectors if the suppressive effects of pre-existing vector-specific immunity in target populations prove clinically relevant. Novel rAd vectors could also be utilized in conjunction with rAd5 vectors or other vectors in heterologous prime-boost vaccine regimens. |
| Session 32—Oral Abstracts Toward Broadly Neutralizing Antibodies against HIV and Advances in HIV Vaccine Development |
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| 99 | TOWARD BROADLY NEUTRALIZING ANTIBODIES AGAINST HIV Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 99) Dennis Burton The progress to date and challenges to be faced in developing an antibody-eliciting component of an HIV vaccine will be critically surveyed. |
| 101 | EV02, A PHASE I TRIAL TO ASSESS THE SAFETY AND IMMUNOGENICITY OF DNA-C FOLLOWED BY NYVAC-C IN AN OPEN, RANDOMIZED COMPARISON TO NYVAC-C ALONE IN HEALTHY VOLUNTEERS AT LOW RISK OF HIV INFECTION Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 101) Pierre-Alexandre Bart1, A Harari1, C Cellerai1, D Ciuffreda1, T Barber2, W Stöhr3, S McCormack3, G Pantaleo1, J Weber2, and EUROVACC Prgm After 48 weeks of follow-up, the vaccines appear safe and well tolerated. The DNA+NYVAC combination is highly immunogenic (>90% responders) and induces vigorous immune responses (500 SFU/106 cells) and polyfunctional CD4 and CD8 T-cell responses lasting in time (80% responders at week 48). |
| 102 | SAFETY AND IMMUNOGENICITY OF THE VRC RECOMBINANT MULTICLADE HIV-1 ADENOVIRAL VECTOR VACCINE ALONE OR IN COMBINATION WITH THE VRC MULTICLADE HIV-1 DNA PLASMID VACCINE IN HEALTHY AFRICAN ADULTS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 102) Kayitesi Kayitenkore1, G Omosa-Manyonyi2, J Bwayo2, E Karita1, W Jaoko2, C Schmidt3, J Gilmour3, M Boaz3, S Than3, and B Graham4 Preliminary safety data suggest that the VRC multiclade HIV-1 DNA and recombinant multiclade HIV-1 adenoviral vector vaccines were generally safe and well tolerated at all doses studied. Both rAd5 dose levels were immunogenic. |
| 103 | SCIENTIFIC OVERVIEW: STATUS OF HIV VACCINE EFFICACY TRIALS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 103) Merlin Robb However, the clinical import of alterations in viral burden among infected volunteers who have received vaccine is not known. Should vaccination produce a favorable reduction in viral burden in any of these studies, additional research will be required to define the associated clinical benefit. |
| Session 34—Symposium Emerging Strategies for the Treatment of HIV |
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| 107 | THE POTENTIAL FOR EXPLOITING HOST RESTRICTION FACTORS FOR THERAPY Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 107) Reuben Harris Strategies to modulate this delicate balance and thereby protect these host APOBEC3 proteins from Vif will be discussed. |
| 108 | NEW AGENTS AND NEW PARADIGMS: THE COMPLEXITY OF CCR5 INHIBITION Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 108) Dan Kuritzkes On balance, small-molecule CCR5 inhibitors remain promising drugs that add significantly to the potency of ART regimens for treatment-experienced patients with CCR5-using virus. Full assessment of their therapeutic potential awaits completion of ongoing clinical trials. |
| 109 | IMPORTANT ISSUES IN THE TREATMENT OF HIV-INFECTED WOMEN: OPTIMIZING ART THROUGHOUT LIFE Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 109) Shahin Lockman1 and J Currier2 The objective of this presentation is to discuss issues related to HIV management (in particular, ART) of women globally, including questions related to the optimal antiretroviral regimen(s) among women (taking into account factors such as CD4 cell count, fertility choices), choice of regimen after exposure to short courses of antiretrovirals during pregnancy, pharmacokinetic and toxicity differences of antiretroviral drugs in women vs men, safety of ART during pregnancy, treatment interruption, etc. Current data on the topic will be reviewed and important gaps in current knowledge discussed. |
| 110 | DO NOVEL ART STRATEGIES HAVE A ROLE IN THE LONG-TERM THERAPY OF HIV INFECTION? Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 110) David Cooper The most pressing need for a strategy trial at this point is the development and execution of “when to start” studies in both the developed and developing world. This question can only be reliably answered in the context of a randomized clinical trial that minimizes the known and unknown factors that bias even well-executed prospective cohort studies. |
| Session 35—Plenary Pathogenesis of Immune Reconstitution Inflammatory Syndrome |
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| 111 | PATHOGENESIS OF IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 111) Martyn French The introduction of ART programs into resource-poor countries has resulted in the treatment of large numbers of very immunodeficient HIV patients who are also infected by pathogens, such as M. tuberculosis and cryptococci. Consequently, IRIS is causing substantial morbidity and mortality and may account for the increased mortality during the first 3 months of ART that has been reported from resource-poor countries. Research priorities include the development of diagnostic methods to differentiate IRD from immunodeficiency disease and a better understanding of the immunopathogenesis so that prevention strategies and treatment can be improved. |
| Session 36—Plenary Viruses, microRNAs, and RNA Interference |
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| 112 | VIRUSES, microRNAs AND RNA INTERFERENCE Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 112) Bryan Cullen Our increasing understanding of the biogenesis of cellular miRNA has led to the development of several methods that allow the introduction of artificial miRNA, also called small interfering RNA (siRNA), into cellular RISC. This process, termed RNA interference (RNAi), can be used to selectively turn off specific cellular or viral genes, in the latter case blocking viral replication. Surprisingly, vertebrate cells do not normally seem to use RNAi as a mechanism of antiviral defense, even though RNAi appears to be an important innate antiviral defense mechanism in plants and insects. Instead, several DNA viruses, including Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpes virus (KSHV), have been found to encode viral miRNA that appear to target host genes involved in antiviral defense. In contrast, RNA viruses such as HIV-1 and hepatitis C virus (HCV) do not encode detectable miRNA in infected cells. In this presentation, I will review our current, as yet limited, understanding of viral miRNA function. |
| Session 37—Oral Abstracts HIV Infection in the Brain: Predictors, Risk Factors, and the Impact of HAART |
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| 113 | THIS IS YOUR BRAIN OFF DRUGS: NEUROCOGNITIVE FUNCTION BEFORE AND AFTER ART DISCONTINUATION IN PATIENTS WITH HIGH CD4 NADIR (ACTG A5170) Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 113) Kevin Robertson1, Z Su2, A Krambrink2, S Evans2, D Havlir3, D Margolis1, D Skiest4, and ACTG 5170 team This study found that patients with preserved immune function who discontinued ART did not experience decreases in neurocognitive function. Sensitivity analyses to adjust for practice effects and the selection bias of ART reinitiation do not completely explain this observation. These findings suggest that healthy patients who elect to stop ART early in the disease will not suffer neurocognitive problems. |
| 114 | HIV-1-ASSOCIATED DEMENTIA ASSOCIATED WITH HIV DNA WITHIN MONOCYTES IN SUBJECTS TREATED OR NOT TREATED WITH ANTIRETROVIRAL MEDICATIONS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 114) Bruce Shiramizu1, C Shikuma1, S Ratto-Kim2, J Ananworanich3, and V Valcour1 HAD is associated with high HIV DNA specifically within activated M/M both in subjects treated or naïve to ART. As it is known that HIV-1 infection of M/M leads to activation of these cells resulting in a more pro-inflammatory phenotype, this study provides an important clue to the pathogenic link between HIV and M/M in the development of HAD. |
| 115 | PREDICTORS OF CEREBROSPINAL FLUID VIRAL BURDEN DURING PRIMARY HIV-1 INFECTION Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 115) Serena Spudich1, M Gisslen2, L Hagberg2, N Lollo1, E Lee1, B Brew3, L Pemberton3, P Cinque4, G Tambussi4, and R Price1 Levels of HIV RNA in the CSF during PHI are most strongly predicted by plasma HIV in subjects with and without neurological symptoms. Both CSF pleocytosis and CSF protein are also independently associated with CSF viral burden during this early period. In subjects with slightly longer than 2 months median duration of infection, CSF HIV RNA levels are not independently correlated with number of days since exposure, despite a trend to decline in parallel with plasma HIV levels. Taken together, our findings suggest that early CSF HIV infection is driven primarily by plasma viral burden. |
| 116 | MRS CAN DETECT HIV-INDUCED INFLAMMATION AND OXIDATIVE STRESS IN THE LENTICULAR NUCLEI Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 116) B Ances1, A Roc2, S Chawla2, M Korczykowski2, D Kolson2, J Detre2, and H Poptani2 As seen by 2-dimensional chemical shift MRS, HIV induces inflammation and oxidative stress in HIV+ patients despite HAART. Lipid and lactate are more sensitive inflammatory biomarkers that can differentiate HIV+ subgroups. These results suggest that additional neuroprotective medications should be considered in HIV neurocognitively impaired patients. |
| 117 | LONGITUDINAL STABILITY OF PSYCHOMOTOR SPEED AND COGNITIVE FLEXIBILITY IN LONG-TERM ASYMPTOMATIC HIV-INFECTED INDIVIDUALS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 117) Michael Cole1, J Margolick2, C Cox2, X Li2, O Selnes2, E Martin3, J Becker4, H Aronow5, and E Miller6 Contrary to recent anecdotal reports, long-term asymptomatic HIV+ individuals did not show evidence of decline in psychomotor speed or cognitive flexibility over 5 years of follow-up. Regardless of whether the asymptomatic status was defined by the absence of AIDS, suppressed viral load, or stable CD4+ lymphocyte count, these areas of cognitive functioning remained stable across a 5-year period. These findings suggest that cognitive decline is primarily associated with persistent viremia and generalized immune system changes rather than duration of infection. Thus, immunological health can be a critical marker of neuropsychological stability over time. |
| 118 | ALTERED DIFFUSION SCALAR METRICS IN THE MIDSAGITTAL CORPUS CALLOSUM ARE ASSOCIATED WITH COGNITION AMONG HIV PATIENTS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 118) David Tate1,2, R Paul3, K Coop1, T Flanigan1, S Zhang4, D Laidlaw4, and K Tashima1 This study demonstrated alterations in FA/MD of the midsagittal corpus callosum with the most alteration occurring in the anterior regions. Furthermore, these alterations are associated with cognitive deficits often observed in HIV-infected patients. Combined, these findings demonstrate the utility of diffusion tensor imaging when examining the CNS and cognitive effects of HIV. |
| 119 | PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY IN THE ERA OF HAART Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 119) David Clifford Review of the current diagnostic criteria, clinical course, and potential approaches to therapy will be discussed. |
| Session 38—Oral Abstracts Primary HIV Infection, Early Treatment, and Immune-Based Therapies for Chronic Infection |
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| 120LB | HIV IN GENITAL FLUIDS DURING HETEROSEXUAL TRANSMISSION Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 120LB) Debrah Boeras1, P Hawkins1, J Mulenga2, S Allen1, and E Hunter1 These initial studies do not support the hypothesis that genetic restriction in the genital tissue is the basis for the extreme genetic bottleneck observed during transmission in HIV discordant couples. Because heterosexual transmission of HIV-1 is the predominant mode of transmission worldwide and non-subtype B viruses prevail in many developing countries, this study directly addresses critical questions about which stage in HIV transmission genetic bottlenecks occur—novel information that will be relevant to the development of vaccines and microbicides. |
| 121 | COMPLEX HIV-1 POPULATIONS PRIOR TO SEROCONVERSION IN MEN WHO HAVE SEX WITH MEN: ANALYSIS OF HIV-1 PLASMA RNA POSITIVE-SERONEGATIVE SUBJECTS FROM THE MACS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 121) Geoffrey Gottlieb1, L Heath1, D Nickle1, K Wong1, A van ’t Wout1, L Jacobson2, J Margolick2, and J Mullins1 In HIV-1 subtype B infection in MSM, multiple envelope variants can be found during acute infection and prior to the establishment of antibody responses. These results demonstrate that early viral populations in MSM can be as diverse as those previously reported in other risk groups, such as those transmitted heterosexually. However, acquisition or early appearance of a complex population of viral variants does not appear to be associated with disease outcome. In contrast, our finding of increasing variable loop length and glycosylation over calendar time may suggest that virus neutralization resistance may be increasing over time of the epidemic. Strategies to prevent HIV transmission will likely have to take these factors into account. |
| 122 | HIV-1 ENVELOPES FROM ACUTE AND CHRONIC INFECTION DIFFER IN THEIR LEVELS OF FUSOGENICITY AND SENSITIVITY TO INHIBITION WITH SCD4 Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 122) Yang Liu1, T Wrin1, N Parkin1, C Petropoulos1, S Frost2, S Little2, D Richman2, and W Huang1 Early HIV infection is characterized by viruses that are predominantly CCR5 using, but utilization of CXCR4 is associated with increased viral loads. Envelopes from acute viremia viruses are more fusogenic and have greater sensitivity to sCD4. This result suggests that the viruses present early in infection are able to spread rapidly through efficient use of cellular CD4 and membrane fusion. This characteristic is lost quickly after the acute phase of infection, possibly due to the influence of the emerging neutralizing antibody response. |
| 123 | IMMUNODOMINATION BY HLA-B27- AND HLA-B57-RESTRICTED HIV-1-SPECIFIC T-CELL RESPONSES RESULTS IN ABROGATION OF OTHER HLA-RESTRICTED RESPONSES IN PRIMARY HIV-1 INFECTION Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 23) Hendrik Streeck1, G Alter1, N Teigen1, M Swartz1, R P Sekaly2, A Kelleher3, S Little4, T Allen1, B Walker1, and M Altfeld1 These data demonstrate that the evolution of HIV-1-specific CD8+ T-cell responses restricted by HLA-A and B alleles is significantly suppressed by the presence of HLA-B27- and HLA-B57-restricted responses during primary HIV-1 infection. Our data in a large cohort of subjects with primary infection also suggest that the combination of different HLA class I alleles, and not the presence of an individual allele, determines the immunodominance patterns of CD8+ T-cell responses during primary HIV-1 infection. |
| 124LB | EARLY TREATMENT OF PRIMARY HIV-1 INFECTION LOWERS THE VIRAL SET POINT Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 124LB) Radjin Steingrover1,2,3, D Bezemer4,5, E Fernandez Garcia3, F Kroon6, F de Wolf4, M Prins5, J Lange1,2,3, and J Prins1 Compared to untreated patients, the viral set point is significantly lower at 7 weeks after interruption of early HAART, but increases over time. The CD4 decline is unaffected by early HAART. Randomized studies are needed to assess the clinical benefit of the lower viral setpoint. |
| 125LB | NO BENEFIT FROM EARLY TREATMENT IN PRIMARY HIV-INFECTION? Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 125LB) Christine Koegl1, E Wolf1, H Jessen2, K Schewe3, M Rausch4, J Goelz5, A Goetzenich6, H Knechten6, H Jaeger7, and the Prime-DAG and Ac-DAG Study Group In this relatively large cohort of acute, primary infected HIV patients, early treatment did not change the viral load set point. However, there was an advantage with regard to immune function: 12 months after seroconversion a median CD4 decrease of –87/µL was observed in untreated patients. In treated patients, 12 months after stopping treatment, CD4 cell count was still increased by +60 µL compared with seroconversion. |
| 126LB | TIME TO ART RESUMPTION FOLLOWING TREATMENT INTERRUPTION IS SHORTER FOR INDIVIDUALS IMMUNIZED WITH HIV-RECOMBINANT CANARYPOX VACCINE (Vcp1452) COMPARED TO PLACEBO: THE MANON-02 TRIAL Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 126LB) Brigitte Autran1, D Costagliola2, R Murphy3, N Wincker4, B Clotet5, J Gatell6, R Tubiana7, S Staszewski8, B Walker9, C Katlama7, and ORVACS Study Group The significant immunogenicity of the HIV-recombinant canarypox vaccine in fully suppressed ART-treated, chronically infected patients is associated with an increased virus production during the post-immunization treatment interruption and therefore to a shortened delay to ART resumption. |
| 127 | REPEATED r-hIL-7 DOSES IMPROVE T-CELL RECOVERY IN HIV-1-INFECTED PATIENTS ENROLLED IN A PHASE I/II MULTICENTRIC STUDY Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 127) Y Levy1,2, Weiss1,3,4, J P Viard5, J Molina6, C Goujard7, F Boué8, S Delluc1, C Rouzioux5, M Morre9, and Jean-François Delfraissy7 A short cycle of r-hIL-7 leads to a significant expansion of T cells in patients who maintained low CD4 counts while on HAART. This effect was observed at the lowest dose (3 µg/kg) without clinical or virological concerns. Results of the whole study will be presented. These results encourage further trials evaluating IL-7 as a novel strategy for improving immune reconstitution in HIV-infected patients. |
| 128 | rhIL7 IN HIV-1-INFECTED SUBJECTS WITH CD4 T-CELL COUNT >100CELLS/µL AND VIRAL LOAD <50,000 COPIES/mL: RESULTS FROM A RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLINDED STUDY (ACTG5214) Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 128) Irini Sereti1, E Aga2, J Spritzler2, A Landay3, S Pahwa4, M Fischl4, D Asmuth5, A Tenorio6, R Buffet7, M Lederman8, and ACTG 5214 team Single-dose rhIL-7 induced T-cell proliferation, down-regulation of IL-7Ra, and transient T-cell increases. The maximum tolerated dose was 30 µg/kg. Biologic activity at all tested doses suggests a favorable therapeutic index of this cytokine for potential use in HIV infection. |
| 129 | IN CHRONIC HIV-1 INFECTION, CYCLOSPORINE A PROVIDES NO SUSTAINED IMMUNOLOGIC BENEFIT TO PERSONS STARTING ART Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 129) Michael Lederman1, L Smeaton2, K Smith3, B Rodriguez1, H Wang2, P Tebas4, S Sieg1, D Margolis5, C Pilcher5, H Valdez6, and AIDS Clinical Trials Group A5138 team CsA coadministered for the first 2 weeks of ART did not provide sustained immunologic benefit to persons with chronic HIV-1 infection. The modest accelerated increase in circulating CCR7+ T cells likely reflects early release from sequestration in lymphoid tissues. If immune activation drives progressive immune deficiency in chronic HIV-1 infection, these activation pathways may not be cyclosporine-sensitive; other pathways of immune activation should be pursued. |
| Session 39—Oral Abstracts Hepatitis B and C: Epidemiology, Pathogenesis, and Treatment |
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| 130 | ACUTE HEPATITIS C IN MEN WHO HAVE SEX WITH MEN IS NOT CONFINED TO THOSE INFECTED WITH HIV, AND THEIR NUMBER CONTINUES TO INCREASE Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 130) Martin Fisher1, D Richardson1, and C Sabin2 There has been, and continues to be a significant increase in acute HCV in MSM. Contrary to current evidence, this phenomenon is not exclusively in MSM with HIV. This would suggest that routine HCV testing is required in all MSM presenting to sexually transmitted disease (STD)/HIV centers. |
| 131 | THE DYNAMICS OF HCV TRANSMISSION AMONG INJECTION DRUG USERS IN ST. PETERSBURG, RUSSIA: SEXUAL TRANSMISSION AND ACQUISITION OF HIV COOPERATIVE AGREEMENT PROGRAM Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 131) Elijah Paintsil1, N Abdala1, L Niccolai1, E Dukhovlinova2, O Toussova2, S Verevochkin2, L Alexander3, A Kozlov2, and R Heimer1 Our data suggest that molecular epidemiological tools could provide data to support or refute transmission within social networks that are exploited in assembling respondent-driven sampling study populations. The ability of respondent-driven sampling to capture transmission patterns for prevalent infections appears limited, but the 2 data sets combined could provide a more robust exploration of incident transmissions of infectious diseases like HCV and HIV. |
| 132 | HCV-SPECIFIC CD8+ T CELLS PRODUCE TGF-β THAT SUPPRESSES HCV-SPECIFIC T-CELL RESPONSES OF HCV-MONO-INFECTED AND HIV-CO-INFECTED SUBJECTS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 132) Nadia Alatrakchi, C Graham, M Exley, and M Koziel Blockade of TGF-β produced by CD8+CD25– could enhance detection of peripheral HCV-specific T-cell responses, even in presence of HIV co-infection. |
| 133 | HIV-SPECIFIC T CELLS ACCUMULATE IN THE LIVER IN HCV/HIV CO-INFECTION Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 133) F Yue, B Valli, D Wong, J Heathcote, C Kovacs, M Loutfy, R Gray, R Halpenny, and Mario Ostrowski Significant numbers of HIV-specific T cells are deposited in the liver of co-infected individuals, resulting in an increase in intra-hepatic viral-specific TNF-α T-cell responses. This mechanism may explain the faster progression of HCV disease in HCV/HIV-co-infected individuals, and further studies examining the effect of cART on this activity and HCV disease progression are warranted. |
| 134 | CpG ADJUVANT + HBV VACCINATION IN HIV INFECTION ACHIEVES LONG-TERM SEROPROTECTION FOR AS LONG AS 5 YEARS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 134) Curtis Cooper1, J Angel1, I Seguin1, D Cote1, H Davis2, and D Cameron1 The immunostimulatory properties of CPG 7909 present an important strategy in achieving long-term hepatitis B seroprotection in HBV vaccine hyporesponsive populations. |
| 135 | SELECTION OF HBV-RESISTANT MUTANTS IN HIV/HBV-CO-INFECTED PATIENTS FAILING ART WITH ANTI-HBV ACTIVITY: IMPLICATIONS FOR DIAGNOSTIC AND VACCINE ESCAPE Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 135) Julie Sheldon1, B Ramos1, A Bartholomeusz2, J Garcia-Samaniego1, P Rios1, M Romero1, S Locarnini2, and V Soriano1 Mutations in the HBV surface antigen following exposure to 3TC are significantly more frequent in HBV genotype A than D, whereas naturally occurring vaccine escape mutants are more frequent in HBV-mono-infected patients with genotype D. HBV genotyping should be performed before starting therapy with anti-HBV active drugs in HBV/HIV-co-infected patients and 3TC (and emtricitabine [FTC]) because single anti-HBV agents should be avoided. The circulation of HBV-encoding envelope mutations selected by antiviral agents requires further investigation to determine whether they may represent a public health concern. |
| 136LB | THE ANTI-HEPATITIS B DRUG ENTECAVIR INHIBITS HIV-1 REPLICATION AND SELECTS HIV-1 VARIANTS RESISTANT TO ANTIRETROVIRAL DRUGS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 136LB) M McMahon1, B Jilek1, T Brennan1, L Shen1, Y Zhou1, S Bhat1, B Hale2, R Hegarty1, R Silicano1, and Chloe Thio1 This study demonstrates that entecavir is a potent (but partial) inhibitor of HIV replication in vivo and in vitro and that it can select for viruses bearing the M184V mutation, which confers high-level resistance to entecavir. These data have important implications for treatment of hepatitis B in HIV-infected patients since they indicate that current guidelines recommending entecavir as the first line treatment in co-infected persons who do not require anti-HIV therapy should be reconsidered. |
| Session 40—Oral Abstracts Clinical Trials, Predictors of Outcome, and Disparities in Care |
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| 137 | INITIAL VIRAL DECAY TO ASSESS THE RELATIVE ANTIRETROVIRAL POTENCY OF PI-, NNRTI-, AND NRTI-SPARING REGIMENS FOR FIRST LINE THERAPY OF HIV-1 INFECTION: ACTG 5160s (SUB-STUDY OF A5142) Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 137) Richard H. Haubrich1, S Riddler2, H Ribaudo3, G DiRienzo3, K Klingman4, K Garren5, T George6, J Rooney7, D Havlir8, J Mellors2, and the AIDS Clinical Trials Group 5160s Study Team Early viral clearance, as evaluated by phase-1 viral load decay and day 7 viral load change, was greater for EFV than LPV or L/E. Phase-1 decay was not different for subjects by gender and race/ethnicity. Day 7 viral load change predicted week-48 virologic outcome. |
| 138 | RANDOMIZED COMPARISON IN TREATMENT-NAÏVE PATIENTS OF ONCE-DAILY VS TWICE-DAILY LOPINAVIR/RITONAVIR-BASED ART AND COMPARISON OF ONCE-DAILY SELF-ADMINISTERED VS DIRECTLY OBSERVED THERAPY Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 138) D Mildvan1, C Tierney2, Robert Gross3, A Andrade4, C Lalama2, S Eshleman4, T Flanigan5, J Santana6, M Dehlinger7, C Flexner4, and the ACTG A5073 Study Team Although overall there was no difference in sustained virologic response between twice daily and once daily LPV/r, twice daily may have an advantage for ART-naïve patients with high viral loads. DOT may have a treatment role while maintained, but there is no evidence of sustained virologic benefit once stopped. |
| 139 | COMPARISON OF PLASMA HIV-1 RNA, CD4 CELL COUNT, AND CD38 EXPRESSION ON CD8 T CELLS AS PREDICTORS OF PROGRESSION TO AIDS AND CD4 CELL DECLINE AMONG UNTREATED PARTICIPANTS IN THE MULTICENTER AIDS COHORT STUDY Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 139) John Mellors1, J Margolick2, J Phair3, C Rinaldo1, R Detels4, L Jacobson2, and A Muñoz2 A single HIV-1 RNA measurement was the best predictor of time to AIDS, explaining almost half of the variability in this clinically relevant outcome. High variance around CD4 regression lines likely accounts for the inability of any marker to explain CD4 cell decline. The predictive value of HIV-1 RNA for time to AIDS reaffirms the central role of viremia in AIDS pathogenesis and strongly supports the use of HIV-1 RNA for patient management. |
| 140 | PREDICTIVE VALUE OF PLASMA HIV RNA LEVELS FOR RATE OF CD4 DECLINE AND CLINICAL DISEASE PROGRESSION Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 140) Bryan Lau, S Gange, G Kirk, S Mehta, B Merriman, and R Moore Our results confirm that HIV RNA has poor predictive value for CD4 slope alone and that any explanation for rate of CD4 slope should account for initial CD4. However, our analysis showing high predictive value for clinical disease events even after adjusting for CD4 levels reinforces the importance of HIV RNA as an independent marker of HIV disease progression. |
| 141 | CARRIAGE OF HLA-Bw4 IS ASSOCIATED WITH LOWER CD4 CELL COUNTS AFTER STARTING HAART: CONSISTENT FINDINGS IN THE WESTERN AUSTRALIAN HIV COHORT STUDY AND THE SWISS HIV COHORT STUDY Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 141) Andri Rauch1, H Furrer1, D Nolan2, E McKinnon2, A Telenti3, and I James2 Carriage of at least one Bw4 allele was associated with lower CD4 cell counts 1 to 5 years after commencing HAART in both cohorts. This finding contrasts the protective effects of Bw4 in untreated HIV-infection and might have implications for timing of treatment initiation as routine HLA typing becomes more common. |
| 142 | DISPARITIES IN SURVIVAL ATTRIBUTABLE TO SUBOPTIMAL HIV CARE IN THE US: INFLUENCE OF GENDER AND RACE/ETHNICITY Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 142) Elena Losina1,2, B Schackman3, S Sadownik1, K Gebo4, R Walensky1,5,6, M Weinstein7, P Lawrence4, W Aaronson1, R Moore4, and D Paltiel8 Full adherence with current US HIV treatment guidelines leads to 9.6 years of life lost from HIV compared to survival in persons without HIV. An additional 5.1 years of life are lost because of late ART initiation and premature ART discontinuation in the United States. Survival losses are higher for Hispanics and blacks than for whites (5.8, 5.3, and 4.3 years, see the figure). Compared with men, Hispanic and black women show greater survival losses, due to higher rates of premature treatment discontinuation. Mean per-person decreases in survival were 6.4 years for Hispanic women compared with 3.9 years for white women. |
| 143LB | THE HIV INTEGRASE INHIBITOR GS-9137 DEMONSTRATES POTENT ANTIRETROVIRAL ACTIVITY IN TREATMENT-EXPERIENCED PATIENTS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 143LB) Andrew R. Zolopa1, M Mullen2, D Berger3, P Ruane4, T Hawkins5, L Zhong6, S Chuck6, J Enejosa6, B Kearney6, and A Cheng6 Both DAVG16 and DAVG24 for GS-9137 125 mg were statistically superior to those for boosted PI. GS-9137 was well tolerated. These data support the evaluation of GS-9137 in phase 3 studies. |
| 144LB | 48-WEEK PRIMARY ANALYSIS OF TRIAL TMC278-C204: TMC278 DEMONSTRATES POTENT AND SUSTAINED EFFICACY IN ART-NAÏVE PATIENTS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 144LB) Anton Pozniak1, J Morales-Ramirez2, L Mohapi3, M Santoscoy4, P Chetchotisakd5, M Hereygers6, S Vanveggel6, M Peeters6, B Woodfall6, and K Boven7 All doses of TMC278 demonstrated significant and sustained efficacy similar to that of EFV over 48 weeks in ART-naïve patients. TMC278 was generally well tolerated with lower nervous system, rash, and lipid effects than EFV. |
| Session 45—Symposium Management of HIV and Sexual Risk in Adolescents |
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| 145 | HIV AMONG ADOLESCENTS AND YOUNG ADULTS IN THE US AND IMPLICATIONS FOR BIOMEDICAL PREVENTION TRIALS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 145) Jonathan Ellen The goal of this presentation to is describe the state of the HIV epidemic among adolescents and young adults in the United States. Specifically, this presentation will: describe trends in incidence of new HIV diagnoses among US adolescents and young adults; compare and contrast trends and risk factors between male and female adolescents; and discuss implications of these data for the inclusion of adolescents and young adults in domestic HIV vaccines and microbicide trials. |
| 146 | THE PRIME OF OUR LIVES: IMMUNOLOGICAL FITNESS AND RECONSTITUTION IN ADOLESCENCE AND EARLY ADULTHOOD Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 146) Paul Krogstad These data may inform discussions with individual patients about the benefits of ART, and projections of the demographic effect on ART in countries heavily affected by the pandemic. |
| 147 | TARGETING ADOLESCENTS FOR HIV VACCINE TRIALS IN SOUTH AFRICA Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 147) Glenda Gray, G de Bruyn, N Skhosana, and J McIntyre Taken together, these preliminary studies indicate that willingness to participate in HIV vaccine trials appears high among Soweto youth and adults. Risk reduction counseling in these trials should also focus on issues such as substance abuse, pregnancy, and depression. |
| 148 | HPV-ASSOCIATED CANCERS AND HIV: WILL HPV VACCINES MAKE A DIFFERENCE? Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 148) Anna-Barbara Moscicki It is expected and hoped that the HPV vaccine will be beneficial to HIV+ children prior to HPV exposure, as expected in non-immunocompromised children. Studies are underway to examine its safety and immunogenecity in this group. Unfortunately, no data are available regarding HPV genital persistence in HIV+ children exposed to HPV at birth. Therefore, efficacy studies in this group are sorely needed. It is also hoped that HPV vaccines will be effective in stopping recurrent infections or reactivation in those HIV+ and HPV-exposed. HPV vaccine could also significantly affect anal and oral cancers in HIV+ persons if administration is timed correctly. |
| Session 46—Oral Abstracts Epidemiology: Transmission Dynamics and Risk |
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| 149 | EXODUS AND GENESIS: THE EMERGENCE OF HIV-1 GROUP M SUBTYPE B Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 149) Michael Worobey1, M Gilbert2, A Pitchenik3, G Wlasiuk1, and A Rambaut4 Our findings establish Haiti as the country with the oldest HIV/AIDS epidemic outside Sub-Saharan Africa. Because of its 40-year history, the HIV-1 epidemic in Haiti exhibits a greater range of viral genetic diversity than the rest of the world’s subtype B strains combined, a fact relevant to vaccine design. The timing of the Haitian origin of the epidemic supports the idea that the genesis of subtype B occurred with the return of 1 of the many Haitian professionals who worked in the Congo in the 1960s. The timing of the subsequent single-patient initiation of the United States and worldwide epidemic shows conclusively that HIV-1 was circulating in the United States for over a decade before the recognition of AIDS in 1981. Our results suggest that the global spread of HIV-1 involves more inertia than previously supposed, with major outbreaks hinging on rare, single transmission events. They also provide compelling independent corroboration of an early 20th century M-group ancestor. |
| 150 | HIV-1 TRANSMISSION DYNAMICS IN AN URBAN NORTH AMERICAN SETTING Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 150) Bluma Brenner1, M Roger2, D Moisi1, J P Routy3, M Wainberg1, and the Quebec PHI Study Group Ours is a North American urban setting in which universal access to ART is available free. The majority of new infections arise from untreated persons at early stages of disease, underscoring the potential benefit of early treatment, as a means of preventing new infections. |
| 151 | DESPITE HAART, HIV-1 IS ONCE AGAIN SPREADING EPIDEMICALLY AMONG MEN HAVING SEX WITH MEN IN THE NETHERLANDS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 151) Daniela Bezemer1, F de Wolf1,2, M Boerlijst3, A van Sighem1, D Hollingsworth2, M Prins4,5, R Geskus4,6, L Gras1, R Coutinho6,7, and C Fraser2 The effect of widespread use of HAART on overall transmission of HIV-1 was offset by an increase in risk behavior. Consequently, HIV-1 is once again spreading epidemically among MSM in the Netherlands. |
| 152 | CORRELATES OF INCIDENT HIV DIAGNOSIS, KNOWLEDGE OF CHEMOPROPHYLAXIS, AND BURDEN OF ACUTE AND RECENT INFECTION AMONG PATRONS OF NEW YORK CITY BATHHOUSES: A PILOT STUDY Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 152) Demetre Daskalakis, MD1, R Silvera1, R Hagerty1, R Hutt, RN1, K Bernstein, PhD1, D Stein1, T Neithercott1, A Brown2, F Valentine, MD1, and M Marmor,PhD1 Screening for HIV at bathhouses accesses a population often missed by traditional testing and preventive programs. Nearly half of those testing HIV+ were recently infected. Given the data implicating early infection with increased infectiousness, this finding highlights the potential effect of early identification on transmission. Additionally, bathhouse interventions, such as this one, may influence HIV transmission to other susceptible populations, given the frequency these MSM reported sex with women. Many of these men test less frequently than recommended by guidelines and are unaware of approved preventive interventions. |
| 153 | POPULATION-BASED PREVALENCE ESTIMATES OF DIAGNOSED AND UNDIAGNOSED HIV AND ASSOCIATED RISK BEHAVIORS AMONG NEW YORK CITY ADULTS, 2004 Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 153) Trang Quyen Nguyen1,2, R Gwynn1, S Kellerman1, E Begier1, R Garg1, K Konty1, M Pfeiffer1, L Torian1, T Frieden1, and L Thorpe1 Although the exclusion of institutionalized groups is a limitation, a smaller proportion of HIV-infected NYC adults was undiagnosed or unreported than previously estimated. Ongoing risky behaviors indicate that more effective prevention interventions are needed, particularly for HIV-infected persons. Low risk perception among adults engaged in high-risk activities highlights the limitations of risk-based testing. Broader, routine screening will enable identification of infected persons not targeted for testing or who do not believe they are at risk. |
| 154LB | IMPACT OF HSV-2 SUPPRESSIVE THERAPY ON GENITAL AND PLASMA HIV-1 RNA IN HIV-1 AND HSV-2-SEROPOSITIVE WOMEN NOT TAKING ART: A RANDOMIZED, PLACEBO-CONTROLLED TRIAL IN JOHANNESBURG, SOUTH AFRICA Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 154LB) Sinead Delany1,2, P Mayaud2, T Clayton2, N Mlaba1, G Akpomiemie1, K Hira3, A Capovilla3, W Stevens3, and H Rees1 HSV-2 suppressive therapy, by reducing HIV-1 plasma viral load and altering the pattern of genital HIV-1 shedding, may contribute to the reduction in sexual transmission of HIV-1 and may delay the requirement for HAART initiation. |
| 155aLB | RANDOMIZED TRIAL OF MALE CIRCUMCISION FOR HIV PREVENTION IN RAKAI, UGANDA Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 155aLB) Ronald Gray1, G Kigozi2, D Serwadda3, F Makumbi2, S Watya4, F Nalugoda2, N Sewankambo4, L Moulton1, A Chaudhury1, M Wawer1, and Rakai Hlth Sci Prgm Male circumcision reduced HIV incidence and genital ulceration, and there was no consistent evidence of behavioral disinhibition. Circumcision can be promoted for HIV prevention in men. Surgical complications are comparable in HIV– and HIV+ men. |
| 155bLB | THE EFFECTS OF MALE CIRCUMCISION ON GENITAL ULCER DISEASE AND URETHRAL SYMPTOMS, AND ON HIV ACQUISITION: AN RCT IN RAKAI, UGANDA Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 155bLB) Maria Wawer1, R Gray1, G kigozi2, F Nalugoda2, T Quinn3,4, F Makumbi2,5, and D Serwadda5 Male circumcision reduced symptomatic genital ulcer disease, but had no effect on urethral symptoms. The reduction in genital ulcer disease associated with circumcision partly accounts for the protective effect of circumcision against HIV infection. |
| Session 47—Symposium Immunopathogenesis: T-Cell Activation and CD4 T-Cell Dysfunction |
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| 156 | THE ROLE OF NEF IN PRIMATE LENTIVIRAL PATHOGENESIS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 156) Frank Kirchhoff In summary, Nef generally enhances the ability of primate lentiviruses to persist efficiently in their respective hosts by facilitating viral evasion of the host immune system and by directly amplifying virus production and infectivity. In most natural primate lentiviral infections the resulting high viral loads are not harmful to the host because Nef prevents high levels of immune activation and apoptosis. Importantly, the inability of HIV-1 to suppress T-cell activation most likely contributes to its high virulence in infected humans. |
| 157 | IMMUNOREGULATION IN HIV INFECTION Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 157) Bruce Walker1, D Kaufmann1, D Kavanagh1, F Pereyra1, J Zaunders2, M Brockman1, E Mackey1, A Rathod1, G Freeman3, and E Rosenberg1 Our data indicate that both PD-1 and CTLA-4 are selectively up-regulated in HIV-specific CD4 T cells and mediate reversible T-cell impairment, identify a unique phenotype among subjects who spontaneously control viremia in the absence of therapy, and provide a potential target to enhance virus-specific function. |
| 158 | UNDERSTANDING THE BENIGN NATURE OF SIV INFECTION IN NATURAL HOSTS: IMPLICATIONS FOR AIDS PATHOGENESIS Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 158) Guido Silvestri In this presentation, I will review and discuss the evidence supporting a key role for the absence of generalized immune activation in maintaining the disease-free state in natural hosts for SIV, and the potential mechanisms underlying the different levels of immune activation in natural versus non-natural HIV/SIV hosts. The implication of these findings in terms of AIDS pathogenesis will be discussed through a systematic analysis of the immunologic similarities and differences between pathogenic and non-pathogenic HIV/SIV infections. Finally, I will comment on how these studies provide a rationale for immune-based therapy targeting the HIV-associated chronic immune activation in HIV-infected patients. |
| 159 | INTERACTIONS BETWEEN REGULATORY T CELLS AND HIV: A COMPLEX BALANCING ACT Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 159) Claire Chougnet1, P Velilla1, J Nilsson2, A Boasso3, J Andersson2, and G Shearer3 Considered together, our findings suggest that HIV directly induces Treg accumulation in lymphoid tissues, and that such accumulation plays an important role in the incapacity of the immune system to control viral replication. They also imply that therapeutic manipulation of Treg number or function in chronically infected patients could improve the outcome of HIV infection. |
| Session 87—Poster Abstracts New RTIs and Pis |
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| 490 | MECHANISM OF SYNERGY BETWEEN EFAVIRENZ AND ZIDOVUDINE: ROLE OF HIV-1 REVERSE TRANSCRIPTASE RNase H ACTIVITY Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 490) Jessica Radzio1,2, and N Sluis-Cremer2 Because AZT potency may be governed by a balance between nucleotide excision and RNase H activity, we hypothesize that the observed increase in RNase H cleavage in the presence of EFV may destroy the RNA template before excision has occurred, leading to dissociation of the template/primer and inhibiting excision. These results might help to explain the observed synergy between AZT and EFV. |
| 491 | PROFILE OF GS-8374, A NOVEL PHOSPHONATE-CONTAINING HIV PI: IN VITRO ANTIRETROVIRAL ACTIVITY, TOXICITY, AND RESISTANCE Conf Retroviruses Opportunistic Infect 2007 Feb 25-28;14: (abstract no. 491) Christian Callebaut1, K Stray1, L Tsai1, L Xu1, G X He1, A Mulato1, T Priskich2, N Parkin2, W Lee1, and T Cihlar1 GS-8374, a phosphonate-containing PI, exhibits a favorable in vitro pharmacology profile with potent antiretroviral activity and low toxicity that has been consistently observed in multiple assay systems. The in vitro resistance profile of GS-8374 is superior to all tested PI, including darunavir. Collectively, these results support further evaluation of this novel PI. |