|
12th Conference on Retroviruses and Opportunistic InfectionsBoston, Massachusetts - February 22-25, 2005 |
Cite as: Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12:abstract no. xx
| Session 3—Symposium Scaling Up HIV Care in the Developing World |
|
| 1 | HIV CARE AND TREATMENT: MODELS OF CARE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 1) Wafaa El-Sadr The characteristics of HIV disease and those of the local environment necessitate that various models of care be established and their effectiveness evaluated. A mosaic of these various models may need to be established in order to meet the needs of all individuals with HIV in a community. |
| 2 | A FAMILY-BASED APPROACH TO PREVENTIVE CARE AND ANTIRETROVIRAL THERAPY IN AFRICA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 2) Jonathan Mermin Expansion of preventive care could improve health for persons with HIV and their families, help achieve public health equity, and lay a foundation for ART. |
| 3 | LABORATORY REQUIREMENTS FOR SCALING UP HIV TREATMENT Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 3) Desmond J Martin and J Sim It is important to choose technologies that are robust, reliable and able to scale up as specimen volumes increase. There should be a quality control programme managed from a central reference laboratory, which is based on technologies that do not rely on traditional communication systems. Cellular phone technology, with built-in communication redundancies, is suitable for this. A working model of such a laboratory configuration supporting an ARV roll out programme in a resource poor setting will be presented. |
| 4 | GETTING ANTIRETROVIRALS TO WHERE THEY’RE NEEDED Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 4) Julian Fleet Despite these important advances toward scaling up ART in developing countries, formidable barriers remain. These include the need for stronger health systems and for far greater numbers of health care and social service workers who can provide HIV testing and counseling, diagnose, prescribe and monitor ART, and provide nutritional support and other care to those in need in developing countries. |
| Session 4—Opening Plenary and Keynote Session Tenth Annual Bernard Fields Memorial Lecture |
|
| 5 | NATURAL RESISTANCE TO HIV INFECTION: THE Vif-APOBEC INTERACTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 5) Michael H. Malim Sequencing of viruses during natural infection indicates that the latter can indeed occur, thus suggesting that perturbation of Vif/APOBEC function deserves consideration as a future therapeutic strategy. |
| 6 | "3 BY 5" PROGRESS, CHALLENGES AND PROSPECTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 6) Jim Kim In the second half of 2004, the number of people on antiretroviral therapy in developing and transitional countries increased dramatically from 440,000 to an estimated 700,000. Experience in the field has given us critical insights regarding the determinants of success in rapidly scaling up HIV treatment and care--and significant encouragement about the feasibility of the project. However, current estimates of those under ARV treatment represent about 12% of the approximately 5.8 million people currently in need in developing and transitional countries. |
| Session 5—Plenary |
|
| 7 | THE HIV ENVELOPE GLYCOPROTEIN: INTERACTIONS AND CONFORMATIONAL CHANGES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 7) Stephen C Harrison The new structure also suggests possible gp120/gp41 interactions in the prefusion trimer and opens the way for design of locked-in gp120 variants, to help determine the antigenic properties of the molecule in a fixed state. |
| Session 6—Plenary |
|
| 8 | CONTROVERSIES IN THE USE OF NEVIRAPINE FOR THE PREVENTION OF MOTHER-TO-CHILD TRANSMISSION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 8) James McIntyre PMTCT interventions have been introduced in many countries, but it is estimated that current programmes still only reach 5% of all HIV-infected pregnant women. Antiretroviral regimens need to remain simple and feasible, while protecting the health of both mothers and children. |
| Session 7—Oral Abstracts and Research Overview Neuropathogenesis: Molecular Markers and Therapeutic Advances |
|
| 9 | HAART IMPROVES NEUROCOGNITIVE IMPAIRMENT IN HIV+ INDIVIDUALS IN UGANDA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 9) Ned Sacktor1, N Nakasujja2, M Wong3, R Skolasky1, K Robertson4, S Musisi2, E Katabira2, and A Ronald5 HAART can be associated with improvement in neurocognitive performance in HIV+ individuals in Uganda. Additional 6-month follow-up data will be obtained to improve our ability to generalize our results to the larger Uganda HIV+ population. A diagnosis of HIV dementia in Sub-Saharan Africa may be an indication for the initiation of HAART if available. |
| 10 | CHEMOKINE AND CYTOKINE PROFILING BY PROTEIN ARRAY TECHNOLOGY SHOWS THE BASAL GANGLIA AS THE MOST AFFECTED AREA IN HIV DEMENTIA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 10) Diana Vargas1, C Nascimbene1, A Lee1, J Williams2, J McArthur1, C Pardo1, and Department of Neurology, HIV Neuroscience group This study demonstrates that cytokines and chemokines are differentially expressed in brain regions in cases of HIV+D and that the basal ganglia appears to have a prominent pro-inflammatory profile as proteins involved in monocyte/macrophage activation were significantly elevated. This pattern of chemokine increase coincided with a marked increase in the magnitude of microglial activation in the basal ganglia. In HIV+D cases, MCP-1 was the only protein consistently elevated in both middle frontal gyrus and basal ganglia, while the expression of IGFBP-2 appeared to be differentially increased in cases of HIV+D with encephalitis as compared with HIV+D without encephalitis. |
| 11 | A HIGH FREQUENCY OF HIV ENVELOPES WITH REDUCED CD4 AND CCR5 DEPENDENCE IN BRAIN COMPARED WITH LYMPHOID TISSUES OF AIDS PATIENTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 11) Elaine Thomas1,2, R Dunfee1,2, D Bogdan3, J Stanton3, K Kunstman3, S Wolinsky3, and D Gabuzda1,2 These results suggest that HIV in the brain may have adapted to use low levels of CD4 and CCR5 for fusion and virus entry to enable efficient infection of macrophages and microglia. These findings have relevance for understanding mechanisms of HIV neurotropism as well as the development of coreceptor inhibitors. |
| 12 | COMPARTMENTALIZED HIV-1 VARIANTS PRESENT IN CEREBROSPINAL FLUID OF ASYMPTOMATIC SUBJECTS ARE PRODUCED BY SHORT-LIVED CELLS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 12) Patrick R Harrington1, D Haas2, and R Swanstrom3 These results suggest that a short-lived infected cell population exists within the central nervous system and contributes to the vast majority of compartmentalized HIV-1 in CSF of asymptomatic patients. We propose a model whereby short-lived, uninfected CD4+ T cells trafficking into the central nervous system amplify the HIV-1 population produced by longer-lived cells in the central nervous system. These findings illustrate the dynamic nature of HIV-1 replication in the central nervous system and raise the possibility that trafficking CD4+ T cells play a role in HIV-1 persistence and pathogenesis in the central nervous system. |
| 13 | EXPERIMENTAL DENERVATION OF THE EPIDERMIS DEMONSTRATED REDUCED REGERATION OF OCICEPTICE FIBERS IN PEOPLE WITH HIV Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 13) Michael Polydefkis*, A Brown, P Hauer, J Griffin, and J McArthur Nerve regeneration occurs and can be rigorously measured over a period of several months in HIV+ subjects. Our results suggest that abnormalities in nerve regeneration precede the development of clinical neuropathy. Regeneration rates for HIV subjects are impaired compared to healthy control subjects and this difference persists even among HIV+ subjects without signs or symptoms of peripheral neuropathy. This is consistent with subclinical pathologic abnormalities being present in nearly all AIDS patients. This approach to nerve regeneration measurement is attractive as an efficient outcome measure for future regenerative HIV-SN peripheral neuropathy trials. |
| 14 | ENHANCEMENT OF HIV-SPECIFIC IMMUNE RESPONSE IN AN ANIMAL MODEL FOR HIV-1 ENCEPHALITIS FOLLOWING PHARMACOLOGIC INHIBITION OF INDOLEAMINE 2,3-DIOXYGENASE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 14) Raghava Potula1, L Poluektova1, B Knipe1, J Chrastil1, D Heilman1, H Dou1, H Gendelman1, D Munn2, and Y Persidisky1 These results indicate that IDO inhibition leads to effective elimination of HIV-1-infected MDM in the brain offering new strategies for therapeutic intervention in HIVE. |
| 15 | PHYLOGENETIC AND SEQUENCE ANALYSIS OF gp160 FROM LONG-TERM PROGRESSING MACAQUES DEMONSTRATES COMPARTMENTALIZATION IN DISTINCT CENTRAL NERVOUS SYSTEM SITES AND TISSUE-SPECIFIC EVOLUTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 15) Maria Chen1, E Ryzhova1, S Westmoreland2, A Lackner3, and F González-Scarano1 Phylogenetic analysis of gp160 demonstrates CNS compartmentalization initiated by independent neuroinvasion events in anatomically distinct CNS sites in long-term but not rapid progression of immunodeficiency. Mutations found in CNS envelopes indicate that evolution of key regions, such as variable loops and CD4-binding domains, may be important for the development of viruses that acquire neuropathogenic potential. |
| 16LB | SIGNS OF NEURONAL DAMAGE AFTER ANTIRETROVIRAL TREATMENT INTERRUPTION IN HIV-1 Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 16LB) Magnus Gisslén1, L Rosengren1, L Hagberg1, and R Price2 These findings suggest that in the setting of treatment interruption, the increase in viremia may result in nervous system injury, albeit asymptomatic, within the time frame of the study. Neurofilament protein is a sensitive marker of axonal injury which in the present setting seems to disclose subclinical injury. Further studies are warranted to examine this issue further. |
| 17 | IMPACT OF HAART ON NeuroAIDS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 17) Ron Ellis Together, these observations argue for a multi-center, randomized clinical trial to evaluate a CNS-targeted antiretroviral treatment strategy. Such a trial would provide the level of evidence needed to formulate ART guidelines specific to HNCI. |
| Session 8—Oral Abstracts Diagnosis and Treatment of HIV Infection in Developing Countries |
|
| 18 | ROUTINE HIV COUNSELING AND TESTING: ACCEPTABILITY, PREVALENCE AND HIV RISK BEHAVIOR Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 18) Rhoda Wanyenze1, C Liechty2, K Ragland2, V Masembe3, H Mayanja-Kizza3, D Bangsberg2, and M Kamya3 We found routine in-patient HIV C&T to be highly acceptable in the medical in-patient setting of an urban sub-Saharan African hospital. Despite acute illnesses that may often be markers of advanced HIV disease, there was significant ongoing HIV risk behavior among medical in-patients. Referral of hospitalized patients for HIV C&T post discharge is a missed opportunity for HIV diagnosis, prevention counseling, and linkage to care. |
| 19 | PREGNANCY AND THE RISK OF INCIDENT HIV IN RAKAI, UGANDA, A CAUSE FOR CONCERN Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 19) Ronald Gray1, X Li1, D Serwadda2, G Kigozi3, F Wabwire Wabwire-Mangen2, H Brahmbhatt1, M Wawer4, and Rakai Health Sciences Program Pregnancy represents a special period of increased risk of HIV acquisition, and there is an urgent need to promote HIV prevention during pregnancy. |
| 20 | REAL-TIME DETECTION OF PATIENTS WITH ACUTE HIV INFECTION IN AFRICA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 20) Susan Fiscus1, C Pilcher1, W Miller1, I Hoffman1,2, M Price1, D Chilongozi2, C Mapanje2, R Krysiak1,2, M Hosseinipour2, S Galvin1,2, S Gama2, F Martinson2, and M Cohen1 These results suggest that a substantial number of people seeking care for acute STD in Malawi have acute HIV co-infection that would be undetected by standard testing. Real-time pooled RNA testing for detection of acute HIV and quality control is feasible at centers of excellence in sub-Saharan Africa; however, parallel rapid testing and p24 antigen testing are technologically simple approaches that together may detect as much as 80% of acute cases. Acutely infected patients are likely to be extremely contagious, and thus deserve special prevention and treatment efforts. |
| 21 | TOXICITIES FROM NEVIRAPINE IN HIV-INFECTED MALES AND FEMALES, INCLUDING PREGNANT FEMALES WITH VARIOUS CD4 CELL COUNTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 21) N Phanuphak, T Apornpong, S Intarasuk, S Teeratakulpisarn, and Praphan Phanuphak Although reported as a cause of life-threatening adverse events, NVP has not caused more frequent adverse events than previously reported in any group of our patients analyzed including, pregnant women with CD4 >250 cells/mm3. There were some trends of increasing gr. III-IV liver toxicities and gr. I-II skin toxicities in pregnant women with CD4 > 250 cells/mm3, but none reached a statistically significant level. With careful clinical and laboratory monitoring no fatality has been observed in this cohort. NVP-based triple regimen should still be considered as an option for PMTCT in pregnant women regardless of CD4 cell counts, especially in middle-income countries. |
| 22 | SHORT-TERM VIROLOGIC RESPONSE TO A TRIPLE NUCLEOSIDE/NUCLEOTIDE ANALOGUE REGIMEN IN ADULTS WITH HIV INFECTION IN AFRICA WITHIN THE DART TRIAL Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 22) Cissy Kityo Mutuluuza1, S Walker2, P Kaleebu3, V Robertson4, R Enzama1, A Burke2, D Yirrell3, A Reid4, P Munderi3, D Gibb2, C Gilks5, P Mugyenyi1, H Grosskurth3, J Hakim4, D Pillay6, and the DART Trial Triple nucleoside regimens are highly relevant in resource limited settings: 27% of DART patients have a prior diagnosis of pulmonary or extra-pulmonary tuberculosis, the latter also being the third most frequently reported WHO grade 4 event after baseline. ZDV+3TC+TDF has good virological efficacy in advanced HIV disease, comparable to that reported after HAART introduction in equivalent industrialised populations, but against a background of intercurrent illnesses. Evaluation of genotypes in those with HIV RNA ≥ 1000 copies/mL at 24 weeks, and response to 48 weeks are ongoing. |
| 23 | RESPONSE TO HIGHLY ACTIVE RETROVIRAL THERAPY IN LOW- AND HIGH-INCOME COUNTRIES: ANALYSIS OF CLINICAL DATABASES FROM 4 CONTINENTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 23) Francois Dabis1, M Schechter2, M Egger3, and ART-LINC/ART-CC STUDY GROUPS Immunologic and virologic response appear to be similar for HIV positive individuals in the two groups of countries. Compared to the pre-HAART era, mortality was reduced substantially both in developing and developing countries. For given baseline CD4 levels, mortality was higher in the developing countries. The difference in early mortality was most pronounced for patients with advanced disease, possibly because a larger proportion of patients in the developing countries presented with severe opportunistic infections. |
| 24 | SEVERE ANEMIA AND ASSOCIATED RISK FACTORS FOLLOWING INITIATION OF ZDV-CONTAINING REGIMENS IN ADULTS WITH HIV INFECTION IN AFRICA WITHIN THE DART TRIAL Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 24) Francis Ssali1, P Munderi2, A Reid3, S Walker4, W Stohr4, C Gilks5, and the DART Trial Although the incidence of grade 4 anemia in DART is higher than expected, this may be partly explained by a higher proportion of women, more advanced disease, and lower hemoglobin at baseline in DART compared to studies in industrialised countries, as well as greater risk of malaria. |
| 25 | ADHERENCE TO ANTIRETROVIRAL THERAPY ASSESSED BY PHARRMACY CLAIMS AND SURVIVAL IN HIV-INFECTED SOUTH AFRICANS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 25) Jean Nachega1,3, M Hislop2, M Lo1, S Omer1, D Dowdy1, L Regensberg2, R Chaisson1, and G Maartens3 Poor ART adherence as assessed by ART claim data is associated with decreased survival. Pharmacy claims may be a simple and effective tool for monitoring adherence as ART programs in sub-Saharan Africa are scaled up. Reasons for poor adherence in males in our study population need to be explored further. |
| 26 | LACK OF HEALTH INSURANCE IS ASSOCIATED WITH LOWER RESPONSE TO HIGHLY-ACTIVE ANTIRETROVIRAL THERAPY IN TREATMENT NAIVE PATIENTS AT A LARGE PRIVATE CLINIC IN BOTSWANA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 26) Gregory Bisson1, J Strom2, R Gross1, X Wang1, T Gaolathe3, N Ndwapi3, H Friedman1, I Frank1, and D Dickinson4 Lack of insurance coverage is associated with failure to achieve an undetectable HIV viral load in the first year after starting HAART in this large private clinic in Botswana. This finding suggests the importance of economic influences on response to HAART in private clinics in resource-limited settings. |
| 27LB | DECLINES IN HIV PREVALENCE IN UGANDA: NOT AS SIMPLE AS ABC Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 27LB) Maria J Wawer1, R Gray2, D Serwadda3, Z Namukwaya4, F Makumbi4, N Sewankambo5, X Li6, T Lutalo7, F Nalugoda8, and T Quinn9 We observed no increase in abstinence or monogamy (no evidence for A or B), but condom use increased in casual relationships (evidence for C). Mortality (death/D) removed ~70 more HIV+ persons per year than were added through new seroconversions, accounting for much of the observed decline in prevalence. HIV incidence and thus the number of HIV transmissions contributed by persons in early stage HIV infection (E) remained relatively stable in this period. ART is unlikely to reduce HIV incidence, since most transmissions occur prior to index partner ART eligibility. Moreover, ART availability may result in behavioral disinhibition, increased risk behavior, and higher HIV incidence. In summary, declines in Rakai HIV prevalence in the past decade are associated primarily with C and D. Prevention of ART-related behavioral disinhibition is crucial to contain the future course of the epidemic. |
| Session 9—Oral Abstracts Cellular and Viral Factors in Virus-Host Interplay |
|
| 28 | STRUCTURAL STUDIES OF AN UNLIGANDED SIMIAN IMMUNODEFICIENCY VIRUS GP120 CORE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 28) Bing Chen2, E Vogan1,2, H Gong2, J Skehel3, D Wiley1,2, and S Harrison1,2 These disulfide-locked mutants are expected to facilitate further crystallographic studies on both the monomeric gp120 and the envelope glycoprotein trimers. They may also be used as selective immunnogens. |
| 29 | HIV-1 VPR HELPS TO PROTECT THE VIRAL GENOME AGAINST APOBEC3-MEDIATED INNATE IMMUNITY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 29) Bärbel Schröfelbauer, Q Yu, and N Landau We conclude that Vpr serves as a secondary system by which the virus further protects itself from deamination, thereby increasing the fidelity with which its genome is replicated. The presence of 2 accessory genes in the viral genome dedicated to prevent the encapsidation of cellular DNA-modifying enzymes highlights the importance of cytidine deamination in the viral life cycle. |
| 30 | A NEW MECHANISM OF ANTIVIRAL DEFENSE BY APOBEC3G Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 30) Ya-Lin Chiu, V Soros, K Stopak, J Kreisberg, W Yonemoto, J Neidleman, and W Greene These findings reveal that low molecular weight form A3G functions as an effective post-entry restriction factor for HIV-1 in resting CD4 T cells. Accordingly, agents promoting high molecular weight form A3G disassembly might effectively block the growth of wild type HIV entering highly permissive cells. |
| 31 | PHOSPHORYLATION OF A NOVEL SOCS-BOX REGULATES ASSEMBLY OF THE HIV-1 Vif-Cul5 COMPLEX THAT PROMOTES APOBEC3G DEGRADATION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 31) Andrew Mehle1, J Goncalves2, M Santa-Marta2, M McPike1, and D Gabuzda1 Vif targets APOBEC3G for degradation by forming a Cul5-EloBC E3 ubiquitin ligase through a novel SOC-box that binds EloC. Vif binding to EloC is negatively regulated by serine phosphorylation in the BC-box motif. The finding that phosphorylation of Vif is important for productive HIV infection but not APOBEC3G degradation raises the possibility that Vif phosphorylation may also regulate another as yet unknown function important for HIV replication. Vif is autoubiquitinated by Cul5, analogous to F-box proteins that are autoubiquitinated within their SCF complex. These findings provide new insights into the mechanisms by which Vif counteracts the antiviral activity of APOBEC3G and also have implications for identifying new therapeutic targets. |
| 32 | SELECTIVE ASSEMBLY OF HIV-1 Vif-Cul5-ELONGINB-ELONGINC E3 UBIQUITIN LIGASE COMPLEX THROUGH A NOVEL SOCS BOX AND UPSTREAM CYSTEINES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 32) Zuoxiang Xiao, Y Yu, E Ehrlich, and X F Yu HIV-1 Vif is a SOCS-box-containing protein that acts as an adaptor protein bridging target protein(s) to E3 ligase complex. The SOCS-box motif of HIV-1 Vif interacting with Elongin C was necessary but not sufficient for interaction with Cul5-ElonginB-ElonginC complex. Our studies suggest that selective assembly with Cul5 vs Cul2 E3 may require protein interfaces in addition to the SOCS-box-ElonginC interaction. |
| 33LB | APOBEC3G HYPERMUTATION AND TY1 RESTRICTION IN YEAST Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 33LB) A Schumacher1, D Nissley2, and Reuben S. Harris1 These data expand the range of APOBEC3 targets and indicate that this innate cellular defense may be part of a more general mobile nucleic acid restriction mechanism poised to withstand internal as well as external assaults. |
| 34 | SPECIES-SPECIFIC VARIATION IN THE B30.2(SPRY) DOMAIN OF TRIM5α DETERMINES THE POTENCY OF HIV-1 RESTRICTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 34) Matthew Stremlau, M Perron, B Song, S Welikala, and J Sodroski Chimeric TRIM5α proteins that are more than 98% identical to the human protein can potently block HIV-1. These proteins may have therapeutic utility, and also provide important mechanistic insights into TRIM5α antiviral activity. |
| 35 | HOST FACTORS AFFECTING THE INTEGRATION OF HIV-1 IN NON-DIVIDING CELLS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 35) Jean-Marc Jacqué and M Stevenson A better understanding of these critical steps in HIV infection will permit the design new therapeutic approaches for intervention of HIV-1 replication. |
| 36 | HIV GAG TRAFFICKING AND ASSEMBLY ARE REGULATED BY THE NUCLEAR HISTORY OF THE GENOMIC RNA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 36) Chad Swanson, M Ahmad, and M Malim Differential use of RNA nuclear export pathways can modulate Gag trafficking and assembly. In human cells, altering the gag-pol RNA nuclear export pathway affects the intracellular trafficking of Gag and its ability to form virion-like particles. In murine cells, the fundamental assembly block appears to be due to a defect in the nuclear history of the RNA because Gag trafficking and virion-like particle formation can be rescued by altering the nuclear RNA export pathway from Rev/RRE/Crm1 to 4xCTE/NXF1. We hypothesize that the nuclear export element modulates cytosolic localization of gag-pol RNA to an assembly permissive microdomain and are currently characterizing RNA binding proteins that may regulate this process. |
| 37LB | UnPAKing HIV REPLICATION: EVIDENCE FOR THE INVOLVEMENT OF GROUP I PAK IN HIV INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 37LB) Deborah Nguyen, K Wolff, H Yin, J Caldwell, and K Kuhen Together, these studies argue that PAK1 rather than PAK2 is the dominant PAK involved in HIV infection, and that PAK1 is involved in multiple stages of HIV infection. Targeting of PAK kinases may represent a novel strategy for development of anti-viral therapeutics. |
| Session 10—Oral Abstracts Complications of Antiretroviral Therapy |
|
| 38 | MIXED PATTERNS OF CHANGES IN CENTRAL AND PERIPHERAL FAT FOLLOWING INITIATION OF ART Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 38) Kathleen Mulligan1, R Parker2, L Komarow2, P Tebas3, S Grinspoon4, G Robbins4, M Dube5, and the ACTG 5005S and 384 Study Teams Individual results obtained by both anthropometry and DEXA show diverse patterns of fat gain and loss over 64 weeks after initiation of ART. In one quarter of subjects, DEXA trunk fat increased while limb fat decreased, but in 69% the changes were in the same direction. In the majority of cases, increases in waist-to-hip ratio were associated with increases in waist circumference without a concomitant decrease in hip circumference. Increases in waist-to-hip ratio that were a result of decreased hip circumference without a concomitant increase in waist circumference also occurred but were less common. |
| 39 | TREATMENT OF HYPERTRIGLYCERIDEMIA IN HIV-INFECTED PATIENTS UNDER HAART, BY (n-3)POLYUNSATURATED FATTY ACIDS: A DOUBLE-BLIND RANDOMIZED PROSPECTIVE TRIAL IN 122 PATIENTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 39) Pierre De Truchis1, M Kirstetter2, A Perier3, C Meunier4, J Gardette4, J C Melchior5, and Maxepa-VIH Study Group This study demonstrates the efficacy of Maxepa® to decrease triglycerides in ART-treated HIV-infected patients with baseline elevated triglycerides; it could represent a potential option for first line therapy for ART-associated hypertriglyceridemia because of its efficacy, good tolerance, and absence of drug interactions. |
| 40 | SWITCH TO A PROTEASE INHIBITOR-CONTAINING/NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR-SPARING REGIMEN INCREASES APPENDICULAR FAT AND SERUM LIPID LEVELS WITHOUT AFFECTING GLUCOSE METABOLISM OR BONE MINERAL DENSITY. THE RESULTS OF A PROSPECTIVE RANDOMIZED TRIAL, ACTG 5125s Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 40) Pablo Tebas1, J Zhang2, K Yarasheski3, S Evans2, M Fischl4, A Shevitz5, J Feinberg6, A Collier7, C Shikuma8, B Brizz9, F Sattler10, and Adult AIDS Clinical Trials Group (AACTG) The switch to a non-NRTI containing combination of LPV/r+EFV was associated with significant improvement in appendicular fat, increases in serum lipids, and stable glucose metabolism and regional bone mineral density. These findings support the observations that LPV/r has minimal effects on glucose metabolism, but is associated with greater increases in triglycerides and cholesterol than a NRTI-containing regimen. These results provide additional evidence that NRTI are important in progressive appendicular fat loss that characterizes HIV-lipoatrophy. The switch to a NRTI-sparing regimen represents a therapeutic option for patients with lipoatrophy. |
| 41 | THE EFFECT OF ROSIGLITAZONE ON PPAR-γ EXPRESSION IN HUMAN ADIPOSE TISSUE IS LIMITED BY CONTINUED EXPOSURE TO THYMIDINE NRTI Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 41) Patrick Mallon1,2, R Sedwell1, G Rogers3, D Nolan4, P Unemori1, H Wand1, K Samaras5, A Kelleher1,2, S Emery1, D Cooper1,2, A Carr2, and The Rosey Investigators In subcutaneous adipose tissue of lipoatrophic, HIV-infected males, the effect of RSG on PPAR-γ expression appears limited by continued exposure to thymidine NRTI. These results provide further insight into the effect of mitochondrial toxicity on PPAR-γ expression and provide a potential molecular explanation for the lack of clinical effect of RSG on limb fat in this patient group. |
| 42 | RELATIONSHIP BETWEEN PROLONGED EXPOSURE TO COMBINATION ART AND MYOCARDIAL INFARCTION: EFFECT OF SEX, AGE, AND LIPID CHANGES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 42) Wafaa El-Sadr1, P Reiss2, S De Wit3, A D'Arminio Monforte4, R Thiébaut5, L Morfeldt6, R Weber7, C Pradier8, G Calvo9, M Law10, O Kirk11, C Sabin12, N Friis-Møller13, J Lundgren13, and On behalf of the D:A:D Study Group These findings suggest that while the overall absolute risk of myocardial infarction remains modest, the risk continues to increase with longer exposure to combined ART over the first 7 years of use. The relative increase in risk appears similar in men and women, and in older and younger subjects. Dyslipidemia explained part but not all of the association of combined ART with risk of myocardial infarction. |
| 43 | A PILOT STUDY OF MITOCHONDRIAL HAPLOGROUPS AND PERIPHERAL NEUROPATHY DURING ANTIRETROVIRAL THERAPY: NWCS238, AN ANALYSIS OF ACTG STUDY 384 Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 43) Todd Hulgan1, J Canter1, J Haines1, M Ritchie1, A Kallianpur1, M Summar1, G Robbins2, R Shafer3, D Clifford4, D Haas1, and the ACTG Study 384 Team Mitochondrial haplogroup T was more frequent in Caucasians who developed subjective peripheral neuropathy while on ddI/d4T during Study 384. The polymorphism that defines this haplogroup is located in the ND5 region of the mitochondrial gene encoding Complex I respiratory transport chain subunits and may point to variations in this gene that predispose individuals to mitochondrial toxicity. Further study of functional mechanisms and confirmation of this association in other cohorts are warranted. |
| 44LB | A 48-WEEK, RANDOMIZED, OPEN-LABEL COMPARATIVE STUDY OF TENOFOVIR DF VS ABACAVIR AS SUBSTITUTES FOR A THYMIDINE ANALOG IN PERSONS WITH LIPOATROPHY AND SUSTAINED VIROLOGICAL SUPPRESSION ON HAART Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 44) Graeme Moyle1, C Sabin1, J Cartledge2, M Johnson1, E Wilkins3, D Churchill4, P Hay5, A Fakoya6, M Murphy7, G Scullard8, C Leen9, G Reilly10, and The Rave Study Group In lipoatrophic HIV-infected adults, switching from a thymidine analog to ABC or TDF for 48 weeks leads to similar, significant increases in limb fat. While both agents maintain virological suppression, TDF is associated with fewer treatment discontinuations and greater improvements in lipid parameters than ABC. |
| 45LB | SWITCHING TO A THYMIDINE ANALOG-SPARING OR A NUCLEOSIDE-SPARING REGIMEN IMPROVES LIPOATROPHY: 24-WEEK RESULTS OF A PROSPECTIVE RANDOMIZED CLINICAL TRIAL, AACTG 5110 Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 45LB) Robert Murphy1, J Zhang2, R Hafner3, A Shevitz4, K Tashima5, K Yarasheski6, J Forand4, B Berzins1, S Owens7, S Evans2, P Tebas8, and AACTG 5110 Study Team In patients with lipoatrophy, switching d4T or ZDV to a nonthymidine analog or changing to a NRTI-sparing regimen is associated with significant improvements in SAT, VAT, and VAT:TAT while maintaining virologic control and improving CD4 with NRTI-sparing. Further follow-up is needed to identify long-term effects. |
| Session 14—Oral Abstracts Pediatric HIV Therapy |
|
| 48 | SAFETY AND CELL-MEDIATED IMMUNE RESPONSES TO PRIME-BOOST IMMUNIZATION WITH ALVAC HIV VACCINE AND AIDSVAX B/B IN NEWBORNS OF HIV-INFECTED MOTHERS (PACTG 326) Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 48) Elizabeth McFarland1, D Johnson2,3, P Muresan4, T Fenton4, J McNamara5, E Hawkins6, B Heckman7, J Read8, S Estep5, M Gurwith9, S Gurunathan10, J Lambert11, and Pediatric AIDS Clinical Trials Group 326 Protocol Team Blinded results in infants suggest that 1452 and AIDSVAX B/B are safe and that immunogenicity is enhanced when given in a prime-boost regimen. Unblinded results will be available at the meeting. |
| 49 | EARLY HAART LIMITS HIV-1 EVOLUTION IN INFECTED INFANTS TREATED FROM INFANCY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 49) J Kajdas1, D Watson2, G Siberry1, A Ahonkhai1, R Ashworth1, T Quinn1, S Ray1, and Deborah Persaud1 HAART initiated in early infancy is highly effective in arresting HIV-1 evolution in pol and env. The persistence of a homogeneous pool of HIV-1 variants due to early effective HAART has important implications for therapeutic HIV-1 vaccine strategy. |
| 50 | EFFECTIVENESS OF NNRTI-BASED HAART IN ART-NAÏVE HIV-INFECTED CHILDREN PARTICIPATING IN THAILAND'S NATIONAL ACCESS PROGRAM: 72-WEEK RESULT Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 50) Thanyawee Puthanakit1, A Oberdorfer1, N Akarathum2, S Kanjanavanit2, P Wannarit3, R Chaiwarith1, and T Sirisanthana1 This study showed that NNRTI-based HAART is an effective regimen for HIV-infected children despite initiation of treatment in the advanced stage of disease. The use of generic fixed-dose formulations and non-pediatric formulations are feasible and effective in resource-limited settings. |
| 51a | A 12-MONTH TREATMENT WITN TENOFOVIR DOES NOT RESULT IN BONE MINERAL LOSS IN HIV-INFECTED CHILDREN Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 51a) Vania Giacomet1, S Mora2, L Cafarelli1, P Erba1, M Sciannamblo2, and A Viganò1 Our data indicate that, in HIV-infected children, 12-month treatment with TDF is not associated with an impairment on bone mineral accrual. |
| 51b | EFFECTS OF HAART SIMPLIFICATION IN HIV-INFECTED CHILDREN Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 51b) Guido Castelli1, M Amicosante2, P Palma1, C Cancrini2, M Romiti2, M Santucci2, A Martino1, and P Rossi1 HAART simplification after an induction therapy allows to maintain a complete and long term virologic control. The progressive increase of specific CTL response observed in some patients can be related to an enhanced viral replication in lymph nodes. The evaluation of proviral DNA is under evaluation and will be presented. |
| 51c | IMMUNE RECONSTITUTION AND PREDICTORS OF VIROLOGIC SUPPRESSION AND BREAKTHROUGH IN ADOLESCENTS ON HAART: WEEK 60 RESULTS FROM THE PACTG 381 COHORT Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 51c) Bret Rudy1, J Lindsey2, P Flynn3, R Bosch2, C Wilson4, M Hughes2, S Douglas1, and Pediatric AIDS Clinical Trials Group 381 Study Team Adolescents achieve lower levels of virologic suppression by weeks 16 to 24 than do adults. However, in those who do achieve early virologic control on HAART, suppression to week 60 is high although total CD4+ T cells remain significantly lower. Further study of the immunologic predictors of virologic failure in this population is warranted. |
| 51d | HLA B44 ALLELE AND B44 SUPERTYPE EFFECT ON THE RESPONSE TO HAART IN HIV-1-INFECTED CHILDREN Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 51d) Akihiko Saitoh1, C Powell2, T Fenton3, C Fletcher4, and S Spector1 The HLA B44 allele and B44 supertype were commonly seen in children who failed to respond to HAART. These data suggest that HIV-1-infected children with the common HLA alleles may be less likely to respond optimally to HAART. |
| Session 15—Symposium Epidemiology of HIV: New Insights |
|
| 52 | ESTIMATING THE GLOBAL BURDEN OF HIV/AIDS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 52) Karen A Stanecki Different information sources and different assumptions are used to create national estimates. The accuracy of these estimates depends critically on the quantity and quality of HIV prevalence data, as well as the assumptions used to translate these data into national estimates of the number of adults living with HIV, new infections and deaths among adults, and the number of children newly infected with HIV, living with HIV, and child deaths. |
| 53 | ROLLING OUT RAPID HIV TESTS IN THE UNITED STATES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 53) Bernard M Branson Rapid HIV testing is feasible, delivers timely and accurate results, and offers unique opportunities to diagnose HIV infection among the estimated 180,000 to 280,000 persons in the U.S. who are currently unaware they are infected. |
54 | HIV EPIDEMICS DRIVEN BY INJECTING DRUG USERS: OBSERVATIONS FROM THE FORMER SOVIET UNION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 54) Kasia Malinowska-Sempruch A number of countries known as the former Soviet Union are now struggling with significant HIV infections attributed to injecting drug use. The presentation will explore the social, economic and political reasons for these epidemics. |
| 55 | THE EPIDEMIOLOGY OF SUBSTANCE USE AND SEXUAL RISK BEHAVIOR AMONG MEN WHO HAVE SEX WITH MEN: IMPLICATIONS FOR HIV PREVENTION INTERVENTIONS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 55) Grant Colfax The correlations between use of specific substances and HIV risk behavior make it clear that interventions to reduce methamphetamine, amyl nitrite, cocaine, and heavy alcohol use among MSM should be tested to determine if reductions in use of these substances are associated with corresponding reductions in sexual risk. Given the different psychological and physical effects of these substances, it is likely that a variety of interventions will need to be developed. To date, few substance-use interventions for MSM have been rigorously tested or have demonstrated sustained reductions in sexual risk behaviors, although several approaches show promise, including pharmacologic, contingency management, and risk-reduction counseling interventions. |
| Session 16—Symposium Chemokine Receptor Blockade: Bench to Bedside |
|
| 56 | PRECLINICAL DEVELOPMENT OF CHEMOKINE RECEPTOR INHIBITORS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 56) Donald E Mosier It will be important to understand the evolution of HIV envelope:coreceptor interactions to use entry inhibitors in the most productive manner. |
| 57 | CLINICAL ACTIVITY AND EFFICACY TRIALS OF CHEMOKINE RECEPTOR INHIBITORS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 57) Daniel Kuritzkes A particular challenge is the occurrence of mixed infection with R5 and X4 virus in patients with advanced disease. Whether drugs that specifically inhibit only a portion of the virus population can contribute to an overall net reduction in plasma viremia is an important objective of ongoing studies. Another concern is whether emergence of X4 viruses will be accelerated by CCR5 inhibition, and if so, what the consequences will be on disease progression. In addition, the long-term safety of CCR5 or CXCR4 blockade remains to be established. Lastly, whether the chemokine receptor antagonists are best used as a component of initial treatment regimens or reserved for use in later regimens must be explored through treatment strategies trials. |
| 58 | CLINICAL PHARMACOKINETICS AND PHARMACODYNAMICS OF CHEMOKINE INHIBITORS: IMPLICATIONS FOR RATIONAL DOSING Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 58) Craig W Hendrix Rational dosing of drugs is best informed by an understanding of both the pharmacokinetics of the drug (concentration-time relationship) as well as the pharmacodynamics of the drug (exposure-response relationship). Armed with an understanding of drug exposure levels which achieve desired efficacy and avoid undesired toxicity combined with the knowledge of how drug concentration changes over time, one can build a useful dose-exposure-response model. This model enhances the ability to rationally choose a dosing regimen that achieves the optimal balance of antiviral effect with minimized toxicity. |
| 59 | RESISTANCE TO HIV CHEMOKINE RECEPTOR ANTAGONISTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 59) Christos J Petropoulos1, W Huang1, J Toma1, S Fransen1, S Bonhoeffer2, and J Whitcomb1 HIV-1 entry inhibitors represent a diverse new class of antiretroviral agents. Virus entry is a multi-step process involving several virus envelope proteins (gp120SU, gp41TM) and host cell receptors (CD4, CCR5, CXCR4). |
| Session 17—Symposium Heart and HAART |
|
| 60 | PATHOGENESIS OF DYSLIPIDEMIA IN HIV Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 60) Lars Berglund Our present understanding of the underlying mechanisms for the metabolic complications in HIV is not complete, although a number of studies have contributed to increase our knowledge in this area. It is likely that multiple pathways are involved and that the background for the metabolic pattern is complex. |
| 61 | CARDIOVASCULAR RISK PREDICTION IN THE GENERAL POPULATION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 61) Jorge Plutzky The need for predicting cardiovascular risk in the general population is obvious. Not only are myocardial infarction (MI) and stroke major causes of morbidity and mortality in the Western world, we now know the atherosclerosis to be a pathologic process that arises over decades, even if its most dangerous complications can happen over minutes. |
| 62 | CARDIOVASCULAR OUTCOMES IN HIV INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 62) Jens D Lundgren1, C Sabin2, R Weber3, A D'Arminio Monforte4, W El-Sadr5, P Reiss6, M Law7, F Dabis9, C Pradier10, S deWit11, I Weller2, A Phillips2, N Friis-Moller1, and on behalf of the D:A:D study group The presence of HIV-specific IgA varied from 15/22 (68%) for gp160 to 4/22 (18%) for gp120. IgAl, IgA2 and Secretory Component were all detected in the majority of IgA positive samples regardless of HIV protein specificity. The presence of IgA did not correlate with stage of the menstrual cycle or stage of HIV disease. No anti-HIV antibodies were detected in any of the "at risk" HIV(-) women. These results suggest 1) that HIV-specific IgG found in CVL samples parallel that found in the serum; 2) HIV-specific IgA is detectable in CVL specimens in some but not all seropositive women; and 3) at least some of the CVL IgA is Secretory-IgA. Larger numbers, longitudinal studies during the menstrual cycle and quantitation of antibodies are needed to weigh the importance of genital tract IgA in HIV transmission and HIV effects in the genital tract. |
| 63 | MANAGING CARDIOVASCULAR RISK AND LIPID DISORDERS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 63) Esteban Martinez In the absence of definitive data, it seems reasonable to evaluate lipid disorders in HIV-infected patients according to the same criteria used in the general population. The impact of individual antiretroviral drugs on lipid parameters should be included among the factors to be considered on prescribing cART. |
| Session 18—Policy Forum |
|
| 64 | THE GLOBAL CHALLENGE OF INFECTIOUS DISEASES: THE EVOLVING ROLE OF THE NIH IN BASIC AND CLINICAL RESEARCH Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 64) Anthony Fauci It is imperative that the infectious disease community collectively develops a 21st-century research vision that will allow us to adapt to evolving research needs, and to rapidly translate basic and clinical findings into practice. The next generation of scientific research will require an unprecedented level of flexibility and collaboration. The success of tomorrow's scientific research will depend on our ability to adapt quickly to emerging challenges by efficiently allocation resources across a broad range of evolving research priorities. |
| Session 19—Plenary |
|
| 65 | LIPODYSTROPHY: FITTING THE PIECES OF THE PUZZLE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 65) Peter Reiss Changes in body fat distribution (lipodystrophy), dyslipidemia and insulin resistance unfortunately are very frequent adverse effects of current combination therapy for HIV-1 infection, and thereby importantly jeopardize the sustained effectiveness of treatment. Both nucleoside analogue reverse transcriptase and protease inhibitors are thought to contribute to the pathogenesis of lipoatrophy in particular, and both drug classes are likely to also be involved in the pathogenesis of lipid changes and insulin resistance both by direct and indirect mechanisms. |
| Session 20—Plenary |
|
| 66 | THE BIOLOGY OF HIV-1 TRANSMISSION AND RE-INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 66) B Chohan1,2, L Lavreys2, S Rainwater1, M Sagar1,2, K Mandaliya3, K Mandaliya, and Julie Overbaugh1 The viruses present during chronic HIV-1 infection are genetically and phenotypically diverse, and thus are likely to differ in their fitness for transmission to a new host. The variants that are most successful at spreading from host to host are important targets for vaccine design, microbicides and other interventions. |
| Session 21—Oral Abstracts Pregnancy and Prevention of Perinatal HIV Transmission |
|
| 67 | HAART IN PREGNANCY: SAFETY, EFFECTIVENESS, AND PROTECTION FROM VIRAL RESISTANCE: RESULTS FROM THE DREAM COHORT Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 67) Leonardo Palombi1, P Germano2, G Liotta1, C Perno1, P Narciso3, A da Cruz Gomes4, M Valls Blazquez5, S Loureiro5, S Ceffa6, M Magnano San Lio2, M Bartolo2, G Guidotti7, and M Marazzi8 The DREAM cohort shows that a public health program with an holistic approach, focused on the administration of HAART during pregnancy, protects mothers’ health, as well as to lower HIV vertical transmission, without a high rate of drug resistance mutations. |
| 68 | GESTATIONAL DIABETES AND ART IN PREGNANT HIV-1-INFECTED WOMEN Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no.68) Maria Isabel Gonzalez-Tome1, J Ramos1, I Solis1, E Muñoz1, S Guillen1, J Almeda2, I Bates3, P Miralles4, J Peña3, P del Barrio5, C Garaulet6, A Gonzalez-Espinola7, S Oñate8, N Salcedo9, P Segovia4, and For the Spanish Cohort of HIV infected mothers -infants pairs In our cohort of HIV-1-infected women the prevalence of gestational diabetes appears to be increased compared to general population. Older age and PI exposure are independent significant risk factors for gestational diabetes. |
| 69 | MODE OF DELIVERY AND POSTPARTUM MORBIDITY AMONG HIV-1-INFECTED WOMEN IN LATIN AMERICA AND THE CARIBBEAN: THE NICHD INTERNATIONAL SITE DEVELOPMENT INITIATIVE PERINATAL STUDY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 69) G Duarte1, Jennifer Read2, R Gonin3, M Losso4, D Chang3, E Cardoso5, R Succi6, L Freimanis3, R de Souza7, M Ceriotto8, and J Korelitz3 The overall proportion of HIV-1-infected women with any postpartum morbidity event in this Latin American and Caribbean cohort with enrollment beginning in 2002 is much lower than described in previous studies. There was no statistically significant difference in the risk of overall or major postpartum morbidity according to mode of delivery, but NECS was associated with a greater risk of minor postpartum morbidity events compared with vaginal delivery. |
| 70 | NO INCREASED MATERNAL MORTALITY ATTRIBUTABLE TO PROLONGED BREASTFEEDING AMONG HIV+ WOMEN IN LUSAKA, ZAMBIA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 70) Louise Kuhn1, P Kasonde2, M Sinkala3, C Kankasa2, K Semrau4, G Aldrovandi5, and D Thea4 There was no evidence of increased maternal mortality attributable to long-term breastfeeding in our randomized study. The finding of increased mortality among women who actually ceased breastfeeding early, which is most likely due to confounding by severity of maternal illness, makes it unlikely that failure to comply with random assignment diluted an adverse effect of breastfeeding. Although HIV-related mortality was high, prolonged lactation did not adversely influence survival of HIV+ women. |
| 71 | ASSOCIATION OF CORD BLOOD NEVIRAPINE WITH SELF-REPORTED TIMING OF DOSE AND HIV-1 TRANSMISSION IN THE HIV NET 012 STUDY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no.71) Brooks Jackson1, T Parsons1, P Musoke2, C Nakabiito2, D Donnell3, T Fleming4, M Mirochnick5, L Mofenson6, M Fowler7, F MMiro2, L Guay1, and HIVNET 012 Cord blood NVP concentration correlated well with self-report of NVP administration and timing of dose before delivery. While NVP cord blood concentration did not correlate with HIV-1 transmission, the number of infants infected between birth and 6 to 8 weeks of age was small (n = 11), limiting statistical power. Additionally, cord blood drug levels reflect only pre-exposure infant prophylaxis, and not the infant post-exposure dose component. The high adherence rate in the HIV NET 012 study supports the simplicity and deliverability of this regimen which allows HIV-infected pregnant women in resource-limited settings to self-administer the NVP tablet at labor onset. The lower efficacy rates of the single-dose NVP regimen reported in some field programs may reflect poorer patient instruction/adherence than seen in HIV NET 012. |
| 72LB | ADDITION OF 3 DAYS OF ZDV+3TC POSTPARTUM TO A SHORT COURSE OF ZDV+3TC AND SINGLE-DOSE NVP PROVIDES LOW RATE OF NVP RESISTANCE MUTATIONS AND HIGH EFFICACY IN PREVENTING PERI-PARTUM HIV-1 TRANSMISSION: ANRS DITRAME PLUS, ABIDJAN, CÔTE D’IVOIRE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 72LB) M L Chaix1, Francois Dabis2, D Ekouevi2, F Rouet3, B Tonwe-Gold4, I Viho4, L Bequet4, G Peytavin5, H Toure4, H Menan3, V Leroy2, and C Rouzioux1 A short-course regimen of ZDV+3TC with sdNVP, together with 3 days of ZDV+3TC post-partum prevents most peri-partum HIV-1 transmission in Africa and minimizes viral resistance to NVP. |
| 73LB | NEVIRAPINE RESISTANCE AND SURVIVAL OF WOMEN RECEIVING HAART SUBSEQUENT TO PREVENTION OF MOTHER-TO-CHILD TRANSMISSION: A POPULATION-BASED STOCHASTIC MODEL Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 73LB) Daniel Westreich, A Van Rie, F Behets, J Eron, and C Van Der Horst Our model suggests that the effect of NVP resistance on mortality may not be apparent for many years; and, once it appears, may be small. Current forecasts, based on short-term follow-up of PMTCT programs involving initiation of HAART < 2 years post-delivery, may exaggerate the influence of NVP resistance on survival. Two main factors may explain our results. First, HIV-infected pregnant women are fairly healthy, with relatively high CD4 counts. Second, HAART can have a sustained effect on survival, even after HAART failure. The long-term effects of NVP resistance on survival appear minor compared with the effects of less-than-universal access to HAART. It follows that concerns about NVP resistance should not slow roll-out of non-HAART PMTCT, and that wide access to HAART will have vast public health benefits in the developing world. |
| 74LB | MATERNAL SINGLE-DOSE NEVIRAPINE MAY NOT BE NEEDED TO REDUCE MOTHER-TO-CHILD HIV TRANSMISSION IN THE SETTING OF MATERNAL AND INFANT ZIDOVUDINE AND INFANT SINGLE-DOSE NEVIRAPINE: RESULTS OF A RANDOMIZED CLINICAL TRIAL IN BOTSWANA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 74LB) Roger Shapiro1, I Thior2, P Gilbert3, S Lockman4, C Wester2, L Smeaton5, L Stevens2, T Ndung'u2, V Novitsky5, E van Widenfelt2, P Mazonde6, T H Lee5, R Marlink5, S Lagakos5, M Essex5, and The Mashi Study Group Adding N/N to ZDV was not superior to ZDV alone, but these results need to be interpreted in the context of feeding strategy and the in utero infection rate. If perinatal SD-NVP is added to ZDV, P/N is similar to N/N and may avoid maternal NVP resistance. |
| 75LB | BREAST-FEEDING WITH 6 MONTHS OF INFANT ZIDOVUDINE PROPHYLAXIS VS FORMULA-FEEDING FOR REDUCING POSTNATAL HIV TRANSMISSION AND INFANT MORTALITY: A RANDOMIZED TRIAL IN SOUTHERN AFRICA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 75LB) Ibou Thior1, S Lockman2, L Smeaton3, R Shapiro4, C Wester1, J Heymann3, P Gilbert5, L Stevens1, T Peter1, S Kim1, J Makhema1, K McIntosh6, R Marlink3, S Lagakos3, M Essex3, and the Mashi Study Team This is the first study to compare 2 different types of intervention to prevent postnatal HIV transmission. The BF+ZDV arm had higher HIV infection and lower mortality rates than the FF arm by 7 months and comparable HIV-free survival rates by 18 months. While the application of these results may differ depending on socioeconomic conditions and public health infrastructure, high rates of HIV-free survival through 18 months of age were achieved with both infant feeding strategies. |
| Session 22—Oral Abstracts Clinical Pharmacology: New Agents, Interactions, and Predictors of Virologic Response |
|
| 77 | PROLONGED DURATION OF CCR5 OCCUPANCY BY 873140 IN HIV-NEGATIVE AND HIV-POSITIVE SUBJECTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 77) S Sparks, K Adkison, A Shachoy-Clark, S Piscitelli, and James Demarest Studies using CCR5-specific monoclonal antibodies demonstrate substantial and prolonged in vivo blood CCR5 receptor occupancy by 873140. At sample times post final dose, when plasma drug levels were undetectable, significant CCR5 receptor occupancy (> 50%) was observed for approximately 5 days. The prolonged CCR5 receptor occupancy suggests a potential mechanism for the sustained antiretroviral effect seen following 873140 administration in HIV+ subjects. Taken together, the data support further evaluation of 873140 in HIV-infected individuals. |
| 78 | PHARMACODYNAMICS OF ANTIRETROVIRAL AGENTS IN HIV-1-INFECTED PATIENTS USING VIRAL DYNAMIC MODELS WITH CONSIDERATION OF DRUG SUSCEPTIBILITY AND ADHERENCE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 78) Hulin Wu1, Y Huang1, E Acosta2, J G Park3, S Yu3, S Rosenkranz3, D Kuritzkes4, J Eron5, A Perelson6, and J Gerber7 Any single factor of pharmacokinetics, adherence, and drug susceptibility did not contribute to long-term virologic response. But their combinations in viral dynamic modeling significantly predicted virologic response. HIV dynamic modeling can appropriately capture the complicated nonlinear relationships and interactions among multiple covariates. |
| 79 | STEADY-STATE PHARMACOKINETICS OF AMPRENAVIR, LOPINAVIR, AND EFAVIRENZ COMBINATION IN HIV-INFECTED PATIENTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 79) Paul Pham1, P Barditch-Crovo1, E Redpath1, T Parson1, W Khan1, C Hendrix1, K Carson1, R Qaqish2, and C Flexner1 At the studied dose of LPV-r 533 mg/133 mg twice daily + APV 750 mg twice daily, the pharmacokinetic profiles of LPV and APV were not significantly different in patients who also received EFV. LPV pharmacokinetic parameters were similar to historical controls receiving LPV-r 400 mg/100 mg twice daily. APV Cmin was similar to that seen with LPV 400 mg/100 mg twice daily + APV 600 or 750 mg twice daily or LPV/r 533 mg/133 mg twice daily + FPV 1400 mg twice daily. |
| 80 | MINIMUM PLASMA CONCENTRATIONS OF NEVIRAPINE AND EFAVIRENZ IN RELATION TO VIROLOGIC FAILURE IN ANTIRETROVIRAL-NAÏVE PATIENTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 80) F van Leth1, B Kappelhoff2, D Johnson3, M Losso4, A Boron-Kaczmarska5, M Saag6, J M Livrozet7, D Hall8, A Huitema2, Ferdinand Wit1, J Beijnen2, J Lange1, and the 2NN Study group There was no clear Cmin of NVP below which the risk of virologic failure was significantly increased. A reasonable probability of therapy success (77%) already existed when the NVP Cmin was above 2.3 mg/L. For EFV, this value was 88% for a cut-off > 1.1 mg/L. Therapeutic drug monitoring should target drug concentrations above these values. |
| 81 | PHARMACOGENETICS OF LONG-TERM RESPONSE TO EFAVIRENZ- AND NELFINAVIR-CONTAINING REGIMENS: NWCS213, AN ANALYSIS OF ACTG 384 Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 81) David W Haas1, L Smeaton2, R Shafer3, G Robbins4, G Morse5, L Labbe6, G Wilkinson1, D Clifford7, M Dube8, R D'Aquila1, V DeGruttola2, R Pollard9, A George1, J Donahue1, and R Kim1 Despite strong associations between genetics variants and plasma pharmacokinetics, we did not find significant associations between CYP2B6 or CYP2C19 variants and long-term responses to EFV- or NFV-containing regimens in this dataset. Further analyses of these SNP to consider gene-gene interactions and other outcome variables are warranted. |
| 82 | AN OPEN-LABEL, NON-RANDOMIZED STUDY OF THE EFFECT OF DEPO-MEDROXYPROGESTERONE ACETATE ON THE PHARMACOKINETICS (PK) OF SELECTED PROTEASE INHIBITORS AND NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS THERAPIES AMONG HIV-INFECTED WOMEN Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 82) Susan Ellen Cohn1, D Watts2, J Lertora3, J G Park4, S Yu4, and the A5093 Team Efficacy of DMPA among HIV+ women does not appear to be altered in the presence of NFV-, EFV-, and NVP-based regimens, with no evidence of ovulation occurring based on progesterone levels through week 12. DMPA was well-tolerated and side effects were similar to those reported in HIV– women on DMPA. NFV- and EFV-based regimens do not appear to be altered by the presence of DMPA. Although NVP AUC levels were higher with DMPA, the increased levels do not appear to be clinically relevant. DMPA appears to be safe and effective for HIV-infected women taking these PI and NNRTI. |
| Session 23—Oral Abstracts and Research Overview Determinants Driving Humoral and Cellular Immunity in Monkeys and Humans |
|
| 87 | ANTIGENIC CONSERVATION AND IMMUNOGENICITY OF THE CO-RECEPTOR BINDING SITE IN HIV-1 SUBTYPES A, B, C, D, F, G, H, AND CRF02 Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 87) Julie Decker1, F Bibollet-Ruche1, X Wei1, S Wang1, D Levy1, C Derdeyn2, S Allen2, E Hunter2, J Hoxie3, E Delaporte4, M Peeters4, B Hahn1, P Kwong5, J Robinson6, and G Shaw1 The co-receptor binding surface of the HIV-1 envelope glycoprotein is inherently highly immunogenic and antigenically broadly cross-reactive. Thus, despite remarkable evolutionary diversity among primate lentiviruses, functional constraints on receptor binding create opportunities for broad humoral immune recognition, which in turn serves to constrain the viral quasi-species. |
| 88 | DEFECTIVE MEMORY B-CELL RESPONSES IN HIV-INFECTED PATIENTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 88) Susan Moir1, A Malaspina1, S Orsega1, J Vasquez1, N Miller1, E Donoghue1, S Kottilil1, M Gezmu1, D Follman1, G Vodeiko2, R Levandowski2, J Mican1, T W Chun1, and A Fauci1 All categories of chronically HIV-infected patients had reduced levels of resting memory B cells compared with HIV-negative individuals. This defect translated into a reduced anti-influenza B-cell memory response following influenza vaccination and was likely a contributing factor to the lower baseline levels of hemagglutinin-inhibition titers observed in HIV-infected patients when compared to HIV-negative individuals with similar vaccine histories. |
| 89 | INFECTIVITY AND NEUTRALIZATION OF SIMIAN IMMUNODEFICIENCY VIRUS WITH FLAG EPITOPE TAG INSERTION IN THE GP120 VARIABLE LOOPS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 89) Melissa E Laird and R Desrosiers These results demonstrate that a specific antibody targeted to the SIV V1 loop can neutralize viral infectivity. Furthermore, more potent neutralization of the V1-tagged SIV239 than the V4-tagged SIV239 suggests that antibodies directed to V1 may be more capable of neutralizing infectivity than antibodies directed to V4. |
| 90 | CONTROL OF HIV REPLICATION IN LONG-TERM NON-PROGRESSORS AND PATIENTS PARTIALLY CONTROLLING DRUG-RESISTANT HIV IS ASSOCIATED WITH HIGH LEVELS OF HIV-SPECIFIC IL-2-PRODUCING CD4+ T CELLS AND LOW LEVELS OF IMMUNE ACTIVATION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 90) B Emu1, E Sinclair1, D Favre1, W Moretto1, R Hoh2, J Martin2, D Nixon1, J McCune1, and Steven Deeks3 Control of HIV replication is most strongly correlated with high levels HIV-specific IL-2+ CD4+ T cells and IFN-γ bright T cells, and low levels of T-cell activation. This immunologic state can be best characterized as one in which the host responds to HIV by expanding but not exhausting HIV-specific memory T cells while maintaining a relatively quiescent immune system. Despite a history of advanced HIV disease, a subset of individuals with multi-drug resistant HIV exhibit an immunologic profile comparable to that in LTNP, suggesting that functional immunity can be reconstituted with partially suppressive HAART. |
| 91 | THE MAJORITY OF CURRENTLY CIRCULATING HIV-1 CLADE B VIRUSES FAIL TO PRIME CTL RESPONSES AGAINST AN OTHERWISE IMMUNODOMINANT HLA-A2-RESTRICTED EPITOPE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 91) Marcus Altfeld1, T Allen1, E Kalife1, N Frahm1, M Addo1, B Mothe2, L Reyor1, X Yu1, G Alter1, M Lichterfeld1, A Sette3, E Rosenberg1, P Goulder1, C Brander1, and B Walker1 These data demonstrate that HLA-A2 is capable of contributing to the acute phase CTL response in infected subjects, but that most currently circulating viruses lack a dominant immunogenic epitope presented by this allele, and suggest that immunodominant epitopes restricted by common HLA alleles may be lost as the epidemic matures. |
| 92 | TRANSMISSION AND ACCUMULATION OF CTL ESCAPE VARIANTS EXPLAINS APPARENT NEGATIVE SELECTION IN HIV Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 92) Alasdair Leslie1, D Kavanagh2, I Honeyborne1, K Pfafferott1, C Edwards1, T Pillay1, L Hilton1, C Thobakgale3, D Ramduth3, R Phillips1, P Klenerrman1, B Korber4, P Kiepiela3, B Walker2, and P Goulder1 Negative associations can arise as a result of positive selection of an escape mutation, which is stable on transmission and therefore accumulates in the population to the point at which it defines the consensus sequence. If an escape variant reaches fixation in the population, the epitope can be considered extinct, as it has been lost as a potential target to the immune system, and evidence for the mechanism by which it arose will disappear. These data help to explain how HIV is evolving at a population level. Understanding the direction of HIV evolution has important implications for vaccine development. |
| 93 | REPERTOIRE, DIVERSITY, AND DIFFERENTIATION OF CD8+ CMV-SPECIFIC T CELLS DETERMINE IMMUNE CORRELATES OF PROTECTION AGAINST CMV AFTER RECOVERY FROM ACUTE CMV EVENTS IN HIV-INFECTED PATIENTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 93) Karim Sacre1, G Carcelain1, N Cassoux1, A M Fillet1, D Olive2, D Vittecoq1, C Katlama1, B Autran1, and The RESTIMOP and ALT study groups The control of HCMV replication after acute CMV events in HIV-infected patients treated with HAART depends both: upon a broad antigenic repertoire and diversity of HCMV-specific CD8 T cells, with preferential recognition of IE1 in the early recovery, switching to pp65 in the late recovery periods, rather than solely on the magnitude; and upon regeneration of early memory CD8 T cells with long term survival capacity directed against both pp65 and IE1. These data show that the repertoire, diversity, and differentiation contribute more strongly than the magnitude of virus-specific T cells alone in the control of persistent viruses such as HCMV. |
| 94LB | DELAY OF HIV-1 REBOUND AFTER CESSATION OF ART THROUGH PASSIVE ADMINISTRATION OF HUMAN NEUTRALIZING ANTIBODIES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 94LB) Alexandra Trkola1, H Kuster1, P Rusert1, B Joos1, M Fischer1, C Leemann1, A Manrique1, M Huber1, A Oxenius2, R Weber1, G Stiegler3, B Vcelar3, H Katinger3, L Aceto1, and H Günthard1 Of 14 patients, 7 responded to the antibody treatment with a clearly delayed or decreased rebound thus providing the first direct evidence that neutralizing antibodies can in principle contain viremia in human HIV-1 infection. By giving first insight on the potency, breadth, and titers of neutralizing antibodies required for in vivo activity, our data underline both the potential as also the limits of HIV-1 vaccines based on humoral immunity. |
| 95 | IMMUNE CORRELATES IN SIV Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 95) L Yant, J Loffredo, T Friedrich, S Martin, D O'Connor, and David I Watkins To determine the mechanism of control, we are investigating the cellular immune responses, viral escape, and viral fitness in these controllers. These unusual macaques may be a model HIV-infected long-term non-progressors, and may be useful in identifying the immune mechanisms underlying their superior viral control. |
| Session 24—Oral Abstracts HIV Drug Resistance: Selection, Persistence, and Impact of Response |
|
| 96 | STRUCTURALLY-RELATED HIV CO-RECEPTOR ANTAGONISTS BIND TO SIMILAR REGIONS OF CCR5 BUT HAVE DIFFERENTIAL ACTIVITIES AGAINST UK-427,857-RESISTANT PRIMARY ISOLATES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 96) Mike Westby, C Smith-Burchnell, D Hamilton, J Mori, M Macartney, N Robas, B Irvine, M Fidock, F Perruccio, J Mills, K Burt, C Barber, P Stephenson, P Dorr, and M Perros Substitution of a key functional group in a series of structurally related HIV co-receptor antagonists leads to biologically significant changes in the way 427res viruses interact with compound-bound CCR5. It appears that subtle differences in the occupation of the binding pocket, in particular around the ECL2 interface, enable some compounds to block replication of 427res strains. Encouragingly, our data indicate that resistance to an HIV co-receptor antagonist will not necessarily lead to drug-class resistance. |
| 97 | RESISTANCE TO ENFUVIRTIDE PROCEEDS THROUGH REPEATED SELECTION OF HR1 MUTATIONS IN DIFFERENT ENV QUASI-SPECIES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 97) Beatrice Labrosse1, L Morand-Joubert2, A Goubard1, S Rochas3, J L Labernardière3, J Pacanowski4, J L Meynard4, A Hance1, F Clavel1, and F Mammano1 Mutations conferring ENF resistance are repeatedly selected in different Env genetic backgrounds, leading to the replacement of dominant virus populations over time. The whole Env genetic context thus appears to play a critical role in the expression and selection of HR1 mutations. |
| 98 | K65R AND T215Y ARE NOT PRESENT ON THE SAME VIRAL GENOME IN PLASMA SAMPLES WITH BOTH MUTATIONS DETECTED BY POPULATION SEQUENCING Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 98) Urvi Parikh1, D Barnas1, C Bixby1, H Faruki2, and J Mellors1 K65R and multiple TAM were rarely detected (< 0.1%) in the same plasma sample by population sequencing. In those samples having both mutations, 65R was not found on the same genome with 215Y/F/I; 65R was rarely present with other TAM. These findings confirm at the genomic level the antagonism and mutual exclusivity of the 65R and the 215Y/F/I pathways of NRTI resistance. |
| 99 | SELECTION OF RESISTANCE MUTATIONS IN CHILDREN RECEIVING PROPHYLAXIS WITH LAMIVUDINE OR NEVIRAPINE FOR THE PREVENTION OF POSTNATAL TRANSMISSION OF HIV Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 99) Marina Giuliano1, C Galluzzo1, E Germinario1, R Amici1, M Pirillo1, L Bassani1, J Vyankandondera2, F Mmiro3, P Okong4, and S Vella1 Post-partum prophylaxis with nevirapine or lamivudine leads almost invariably to the selection of resistance mutations in the children who are diagnosed with the infection while receiving these drugs; this should be considered when choosing the antiretroviral regimen for these children. The presence of resistance-associated mutations in untreated women in Africa needs to be evaluated in a larger sample. |
| 100 | RESISTANCE EMERGES IN THE MAJORITY OF WOMEN PROVIDED INTRAPARTUM SINGLE-DOSE NEVIRAPINE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 100) Jeffrey Johnson1, J F Li1, L Morris2, N Martinson3,5, G Gray4, J McIntyre4, and W Heneine1 The finding of K103N in an additional 40% of women with previously undetectable resistance suggests that only a minority of women receiving SD-NVP do not develop resistance mutations, and that conventional sequencing substantially underestimates the emergence of resistance. Real-time testing for other NVP-associated mutations may show that the proportion of women with undetectable resistance is even smaller. These data emphasize the importance of assessing the clinical implications of resistant variants. |
| 101 | PERSISTENCE OF NNRTI-r RESISTANT VARIANTS AFTER SINGLE-DOSE NEVIRAPINE IN HIV-1 SUBTYPE-C-INFECTED WOMEN Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 101) Sarah Palmer1, V Boltz1, F Maldarelli1, N Martinson2,3, G Gray3, J McIntyre3, J Mellors4, L Morris5, and J Coffin1 NNRTI-resistant variants selected by single-dose NVP can still be detected by allele-specific RT-PCR in the majority of women 6 months after standard genotyping becomes negative. The frequency of NNRTI-resistant mutants declines with time after single-dose NVP but can remain above pretreatment levels for at least 1 year. |
| 102 | SENSITIVE REAL-TIME PCR QUANTIFICATION OF 103N RESISTANCE MUTANTS FOLLOWING SINGLE-DOSE TREATMENT WITH NEVIRAPINE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 102) Shayne Loubser1, P Balfe2,5, G Sherman3, S Jones3, S Cohen1, L Kuhn4, S Hammer4, and L Morris1 Real-time PCR shows greater sensitivity for the detection of 103N mutants than in population sequencing. 103N mutants faded over time in RNA among all but a subset of single-dose NVP-exposed women. We found no evidence for archiving of 103N mutations in DNA at 1 year post-single-dose NVP. |
| 103 | EFFECTIVENESS OF SINGLE-DOSE NEVIRAPINE IN A SECOND PREGNANCY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 103) Neil Martinson1,2, L Pumla2, L Morris3, M Ntsala3, A Puren3, C Chezzi3, P Dhlamini2, S Cohen3, G Gray2, J Steyn2, and J McIntyre2 Preliminary data from this pilot study suggest that HIV-transmission in women receiving sdNVP a second time is higher than multiparous controls. However, the rates in cases are similar to other studies in the same population who have been exposed to sdNVP only once. Controls appear to have more advanced HIV which could explain higher resistance levels. Numbers of women attending PMTCT programs for a second or third time are increasing and data is urgently needed to better inform decision-making. |
| 104 | EFFECT OF BASELINE GENOTYPE ON RESPONSE TO TIPRANAVIR/RITONAVIR (TPV/R) COMPARED WITH STANDARD-OF-CARE COMPARATOR (CPI/R) IN TREATMENT-EXPERIENCED PATIENTS: THE PHASE 3 RESIST-1 AND -2 TRIALS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 104) J Schapiro1, P Cahn2, B Trottier3, F Antunes4, D Jayaweera5, J Gerstoft6, D Norris7, D Cooper8, C Hicks9, S McCallister10, D Hall10, H Valdez10, D Neubacher10, V Kohlbrenner10, and D Mayers10 These results indicate that the efficacy of TPV/r-based therapy was consistently superior to CPI/r in this cohort of treatment-experienced HIV+ patients regardless of the number of total baseline protease mutations, primary PI mutations, or key mutations. |
| 105 | PREDICTION OF EARLY HIV-1 RNA REDUCTION IN THE JAGUAR STUDY USING PHENOTYPIC SUSCEPTIBILITY TO DIDANOSINE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 105) Michael Bates1, P Flandre2, K Ryan3, A G Marcelin4, J F Maa3, D Seekins3, C Chappey1, V Calvez4, M C Bernard5, and J M Molina6 The relationship between phenotypic fold change to ddI and virologic response describes a continuum of susceptibility. At low fold change values (£ 1.3) in these highly experienced patients, the majority of patients responded. These patients also experienced the largest drops in viral load from baseline. Patients with intermediate fold change values (1.3 < fold change < 2.2) had approximately a 50% probability of responding while patients with fold changes3 2.2 had a lower probability (29%) of responding to ddI. As such, these data suggest the existence of a fold change range of intermediate probability of response not appreciated previously. |
| Session 28—Symposium Critical Pediatric Issues in Developing Countries |
|
| 106 | SAFER BREASTFEEDING FOR BABIES BORN TO HIV-POSITIVE MOTHERS: PART OF THE ANSWER TO A DILEMMA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 106) Jean Humphrey1,3,4, E Piwoz2,4, P Iliff3,4, N Tavengwa4, and E Marinda4 Compared with EBF, MBF was associated with a 4.03 (95% CI: 0.98, 16.61), 3.79 (95% CI: 1.40-10.29), and 2.60 (95% CI: 1.21-5.55) greater risk of PNT at 6, 12, and 18 months, respectively. PBF was associated with a 1.6 – 2.6 greater (NS) risk. Mothers exposed to the program were 70% more likely to learn their HIV status early (< 3 mo) and 8.4 times more likely to EBF. Each additional program contact was associated with a significant reduction in PNT. |
| 107 | IS EARLY DIAGNOSIS OF HIV INFECTION FEASIBLE IN RESOURCE-LIMITED SETTINGS? Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 107) Christine Rouzioux1, F Rouet2, D Ekouevi2, M Burgard1, M Chaix1, and F Dabis3 Access to treatment for HIV-infected children is one of the most important challenges for the next two years. Thus, early HIV diagnosis in children is one of the first critical issues which needs implementation within the health infrastructures. |
| 108 | ANTIRETROVIRAL THERAPY FOR HIV-INFECTED CHILDREN IN RESOURCE-LIMITED SETTINGS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 108) Diana Gibb The most efficient and cost effective way to reduce paediatric HIV globally is to reduce mother-to child transmission. However, in resource-limited settings, only 10% of pregnant HIV infected women access antenatal services, and single dose nevirapine used in women who subsequently breastfeed has limited efficacy. Even if coverage were 80% today, over 300,000 new paediatric infections would still occur annually. The necessity for treatment alongside prevention is therefore increasingly recognized, the goal being family-based therapy for practical (to avoid pill sharing) and ethical reasons. Nevertheless, the current reality is that even successful programmes struggle to include children – in 2004, only 7% of 25,000 patients on HAART in MSF projects were children. Barriers include difficulties with early diagnosis; procurement, high cost and inadequate availability of appropriate paediatric expertise. In addition, data required for forecasting children’s needs, such as numbers of infected children, natural history and predictors of progression, are lacking. |
| 109 | ADDING INSULT TO INJURY: CHILDHOOD TUBERCULOSIS AND THE HIV EPIDEMIC Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 109) Peter R Donald Atypical mycobacterioses appear to be relatively infrequent in TB high incidence communities even in the presence of high HIV infection rates. In a published study from our hospital of 183 mycobacterial isolates from 49 HIV-infected infants, M bovis BCG was identified from 5 children (10%) and in 2 cases was isolated from gastric aspirate, but no other mycobacteria, other than M tuberculosis. The inherent resistance of certain BCG strains to low concentrations of isoniazid and to pyrazinamide should be kept in mind when treating disseminated BCG. |
| Session 29—Symposium Recent Advances in HIV Vaccine Development |
|
| 110 | HIDE AND SEEK: EVASION AND EXPOSURE OF THE HIV ENVELOPE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 110) Peter D Kwong, L Chen, C C Huang, S Majeed, G Ofek, and T Zhou The HIV envelope employs a variety of mechanisms to evade antibody neutralization. But not all viral isolates nor all portions of the envelope are equally protected. Two extremes are the V3 and the membrane-proximal regions, both of which are about 30 amino acids in size. |
| 111 | VIRAL VECTORS AS HIV VACCINES: LESSONS LEARNED AND FUTURE PROSPECTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 111) Phillip Johnson Viral vectors that serve as a means for non-self (foreign) gene delivery have shown great promise in animal models for a variety of vaccine applications. Yet, with over 20 years of experience, such vectors have not reached the level of FDA-approved human use. This general experience is also true for HIV vaccines based on a variety of viral vector systems. Several major issues have arisen that have impeded progress. |
| 112 | CTLs: ALL T CELLS ARE NOT CREATED EQUAL Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 112) M Juliana McElrath Vaccines that prevent HIV-1 infection will likely need to elicit both broadly neutralizing antibodies and T cells, particularly HIV-1-specific CD8+ cytotoxic T lymphocytes (CTL). Functionally intact CTL are required for the successful control of HIV-1 infection, and rapid CTL effectors at the site of initial infection may ultimately provide the best benefit. |
| 113 | Nonhuman Primate HIV Vaccine Studies: Will They Be Predictive? Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 113) Norman L Letvin Various nonhuman primate models are used to evaluate HIV vaccine strategies. However, there are limited data available to determine the extent to which any of these models might predict the immunogenicity of candidate vaccines in humans or the clinical protection in humans that might be conferred by immunization. Examples will be reviewed of the immunogenicity of candidate HIV vaccines that have been evaluated both in rhesus monkeys and in humans. |
| Session 30—Symposium Antiretroviral Drug Discovery: Exploiting New Targets |
|
| 114 | RNASE H: CAN SELECTIVE INHIBITORS BE IDENTIFIED? Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 114) Michael A Parniak HIV carries its genome as (+)RNA, but must replicate through a double strand DNA intermediate. All steps in the conversion of viral (+)RNA into dsDNA are catalyzed by the viral enzyme, reverse transcriptase (RT), and this requires RT to be multifunctional. |
| 115 | THE DESIGN AND DEVELOPMENT OF HIV-1 INTERGRASE INHIBITORS: PAST, PRESENT AND FUTURE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 115) Daria Hazuda Integrase remains a promising target for the development of novel antiretroviral agents to treat HIV-1 infection. The viability of integrase as a therapeutic target has been validated in vitro as well as in experimental animal model systems of retroviral infection and clinical proof of concept has now been achieved in HIV-1 infected patients. |
| 116 | ASSEMBLY AND RELEASE: NEW TARGETS FOR ANTIRETROVIRALS? Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 116) A Waheed, C Adamson, A Ono, and Eric O Freed HIV-1 particle production is a multistep process that begins with the transport of the newly synthesized Gag polyprotein precursor to the site of assembly, which, in most cell types, is the plasma membrane. We have recently observed that the localization of HIV-1 assembly is regulated by the plasma membrane levels of the phosphoinositide PI(4,5)P2, indicating that this lipid is a cellular cofactor for Gag targeting. |
| 117 | HIV PROTEASE: CAN BETTER INHIBITORS BE FOUND? Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 117) Dale J Kempf The introduction of HIV protease inhibitors (PIs) in the mid 1990s revolutionized the treatment of HIV infection. Eight PIs are currently available |