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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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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-Mřller13, 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 |
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| 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 Viganň1 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 Muńoz1, S Guillen1, J Almeda2, I Bates3, P Miralles4, J Peńa3, P del Barrio5, C Garaulet6, A Gonzalez-Espinola7, S Ońate8, 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 |
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| 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 |
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| 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 |
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| 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 Labernardičre3, 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 |
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| 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 |
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| 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 |
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| 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, and more are in development, particularly for use in individuals infected with drug-resistant virus. Nonetheless, the usefulness of the PI class is still limited by GI side effects, relatively high pill burden, drug-drug interactions (affecting both PI and concomitant medication pharmacokinetics), metabolic complications (e.g., hyperlipidemia, insulin resistance, hyperbilirubinemia), and concern over long-term manifestations (lipodystrophy and cardiovascular disease). |
| Session 31—Oral Abstracts Hepatitis Virus Co-Infection |
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| 118 | COMPARISON OF HEPATITIS C VIRUS-SPECIFIC T-CELL RESPONSES IN PERIPHERAL BLOOD OF SUBJECTS WITH CHRONIC HCV INFECTION WITH VERSUS WITHOUT HIV CO-INFECTION WHEN BLOCKING THE CYTOKINES INVOLVED IN SUPPRESSOR ACTIVITY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 118) Nadia Alatrakchi1, C S Graham1, K E Sherman2, and M J Koziel1 These data demonstrate that blocking of Treg-associated immunoregulatory cytokines may significantly amplify the HCV specific T-cell responses in PBMC of chronic HCV infection even when co-infected with HIV. This may explain the low frequency of HCV-specific responses observed in PBMC. |
| 119 | EVIDENCE FOR A DEFECT IN THE HCV-SPECIFIC CD4+ T-CELL RESPONSE IN HIV/HCV CO-INFECTED INDIVIDUALS OCCURRING AT EARLY STAGE OF HIV INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 119) Valerie Dutoit, D Ciuffreda, J J Gonvers, and G Pantaleo HCV-specific T-cell responses were detected in a similar proportion in HCV-mono-infected and HIV/HCV-co-infected patients. However, the HCV-specific T-cell response was narrowed in HIV/HCV-co-infected individuals and mostly composed of CD8+ T-cell epitopes. These results may provide new insights in the pathogenesis of the progressive course of HCV disease in HIV/HCV-co-infected individuals. |
| 120 | CAN ROUTINE NON-INVASIVE TESTS PREDICT LIVER HISTOLOGY IN HIV/HCV CO-INFECTION? ANALYSIS OF PATIENTS ENTERING THE AIDS PEGASYS RIBAVIRIN INTERNATIONAL CO-INFECTION TRIAL (APRICOT) Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 120) Richard Sterling1, E Lissen2, N Clumeck3, R Sola4, M Correa5, J Montaner6, M Sulkowski7, F Torriani8, D Dieterich9, D Thomas7, D Messinger10, and M Nelson11 Noninvasive tests can accurately predict hepatic fibrosis and may reduce the need for liver biopsy in some HIV/HCV-co-infected patients. The utility of a novel index (FIB-4) using routine laboratory tests requires further study. |
| 121 | UNEXPECTED SIGNIFICANT LIVER DISEASE AMONG HIV/HCV-CO-INFECTED PERSONS WITH MINIMAL FIBROSIS ON INITIAL LIVER BIOPSY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 121) Mark Sulkowski, S Mehta, M Torbenson, R Moore, and D Thomas Unexpectedly > 25% of co-infected patients with mild fibrosis on initial liver bx had significant fibrosis on subsequent bx. If confirmed by others, these data do not support the application of current HCV treatment guidelines to HIV-infected patients on the basis of a single liver biopsy, and suggest that such patients should be closely monitored for liver disease progression. Additional research is urgently needed to identify better predictors of liver disease stage and progression in co-infected patients. |
| 122 | HOMOSEXUALLY TRANSMITTED HCV ACUTE INFECTION RELATED TO A CLUSTERED GENOTYPE 4 HCV IN HIV-1-INFECTED MEN AND INEFFICACY OF EARLY ANTIVIRAL THERAPY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 122) Marie-Laure Chaix1, J Serpaggi2, D Batisse3, C Dupont4, A Vallet-Pichard2, H Fontaine2, J P Viard5, C Piketty3, E Rouveix4, C Rouzioux1, L Weiss3, and S Pol2 These results demonstrate a risk of sexual transmission of HCV in HIV-infected men who have sex with men; a cluster of HCV genotype 4d suggesting a common source of infection and the breakthrough of preventing counseling; and an inefficacy of early treatment with standard interferon of acute hepatitis C in HIV-infected patients to prevent chronic evolution of hepatitis C. |
| 123 | ENTECAVIR IN HIV/HBV-CO-INFECTED PATIENTS: SAFETY AND EFFICACY IN A PHASE II STUDY (ETV-038) Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 123) Wilkin Pessoa1, B Gazzard2, A Huang3, C Brandao-Mello4, L Cassetti5, M Correa6, V Soriano7, P Phiri8, A Hall8, E Ledesma8, and R Wilber8 In HIV/HBV-co-infected patients with 3TC-resistant HBV, adding ETV therapy results in rapid and clinically significant reductions in HBV DNA and normalization of ALT within 24 weeks, with comparable tolerability to placebo. No interference with HIV infection or HAART was observed. ETV is the first selective HBV antiviral to demonstrate safety and efficacy in this population. |
| 124 | TENOFOVIR DISOPROXIL FUMARATE IS NOT INFERIOR TO ADEFOVIR DIPIVOXIL FOR THE TREATMENT OF HEPATITIS B VIRUS IN SUBJECTS WHO ARE CO-INFECTED WITH HIV: RESULTS OF ACTG A5127 Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 124) Marion Peters1, J Anderson2, P Lynch3, J Jacobson4, K Sherman5, B Alston Smith6, S Swindells7, T Liu2, V Johnson8, R Pollard9, J Rooney10, B polsky4, and AACTG 5127 team Both ADV and TDF successfully lower HBV DNA and are safe and efficacious in HIV/HBV co-infected subjects over 48 weeks. ALT flares occur but did not lead to decompensation in these compensated subjects. |
| Session 32—Plenary |
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| 126 | VACCINE PROTECTION AGAINST HUMAN PAPILLOMAVIRUSES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 126) Kathrin U Jansen Human papillomaviruses (HPVs) infect cutaneous, genital, oral and respiratory epithelia in a tissue-specific manner. Infection with HPVs is widespread throughout the world, and viral infection is closely associated with both benign and malignant lesions. The causal link of HPV and cervical cancer has been clearly established both from population based studies as well as animal models. |
| Session 33—Plenary |
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| 127 | MAKING SENSE OF HIV DISEASE PATHOGENESIS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 127) Daniel Douek The mechanisms underlying CD4+ T-cell depletion in HIV infection are not well understood. Comparative studies of lymphoid tissues, where the vast majority of T cells reside, and peripheral blood can potentially illuminate the pathogenesis of HIV-associated disease. |
| Session 34—Oral Abstracts and Research Overview Prevention Strategies: Vaccines and Microbicides |
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| 128 | VAGINAL APPLICATION OF A SMALL MOLECULE CCR5 INHIBITOR PROTECTS MACAQUES AGAINST VAGINAL SHIV 162P TRANSMISSION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 128) Ronald Veazey1, P Klasse2, J Dufour1, M Springer3, and J Moore2 These results demonstrate that topical application of a small-molecule inhibitor of CCR5 can completely protect macaques against vaginal SHIV 162P transmission. Since CCR5- utilizing strains predominate in early mucosal transmission, these findings suggest that targeting CCR5 is sufficient to block vaginal SHIV transmission, and that small-molecule inhibitors may be an effective and economical strategy for preventing mucosal HIV-1 transmission. |
| 129 | MICROBICIDAL POTENTIAL OF RNA INTERFERENCE IN VIVO Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 129) Patricia Cristofaro and B Ramratnam Direct mucosal application of liposome-complexed siRNA leads to gene-specific silencing in cervico-vaginal epithelia. RNAi may be exploited to knock down the vaginal expression of gene products such as CCR5 and thereby may emerge as a novel HIV-1microbicide. |
| 130 | A NOVEL HIV-1-NEUTRALIZING ANTIBODY THAT TARGETS A HIGHLY CONSERVED REGION OF THE VIRAL FUSION MACHINERY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 130) Romas Geleziunas1, A Pessi2, E Bianchi2, G Barbato2, R Hrin1, M Lu1, H Zhang1, S Lennard3, D Lowe3, P Ingallinella2, G Ciliberto2, R Cortese2, D Hazuda1, J Shiver1, and M Miller1 Collectively, these new findings reveal that D5 interacts with a highly conserved epitope located in the hydrophobic pocket formed by the gp41 HR1 region. Future studies will be aimed at exploiting this novel conserved epitope in vaccination strategies by attempting to elicit polyclonal D5-like antibodies in experimental animals using synthetic peptides containing the HR1 hydrophobic pocket. |
| 131 | DYNAMIC IMMUNE RESPONSES MAINTAIN CYTOTOXIC T-LYMPHOCYTE EPITOPE MUTATIONS IN TRANSMITTED SIV VARIANTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 131) Dan Barouch1, J Powers2, F Peyerl1, M Kuroda1, V Hirsch3, D Montefiori4, A Carville5, K Mansfield5, K Kunstman2, S Wolinksy2, and N Letvin1 These data suggest that viruses with mutations in dominant CTL epitopes can prove highly pathogenic when transmitted to naïve hosts. Moreover, mutations in dominant HIV-1 CTL epitopes may accumulate in human populations with limited major hystcompatibility complex heterogeneity by a mechanism involving dynamic CTL control of transiently reverted WT viruses. |
| 132 | CONTROL OF VIREMIA AFTER ANTIRETROVIRAL TREATMENT AND THERAPEUTIC VACCINATION WITH NOVEL FORMS OF DNA VACCINES IN CHRONICALLY SIVMAC251-INFECTED MACAQUES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 132) B Felber1, A von Gegerfelt1, M Rosati1, C Alicea1, P Roth1, J Bear1, A Valentin1, J Boyer2, D Weiner2, N Bischofberger3, P Markham4, P Albert5, G Franchini5, and George Pavlakis1 The combination of novel forms of DNA vaccines administered during ART treatment induced an immune response able to control viremia after removal of ART. Importantly, animals able to control virus maintained this ability for more than a year after ART termination. Therefore, optimized DNA vectors may be beneficial either alone or in combination with other vaccine modalities as an addition to antiretroviral treatment. |
| 133LB | SUSTAINED CONTROL OF VIREMIA FOLLOWING THERAPEUTIC IMMUNIZATION IN CHRONICALLY HIV-1-INFECTED INDIVIDUALS: LONG-TERM FOLLOW-UP OF THE ANRS 093 TRIAL Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 133LB) Yves Levy1, C Durier2, V Meiffredy2, H Gahery-Segard3, A S Lascaux1, C Goujard4, J P Cassuto5, C Rouzioux6, R El Habib7, M Beumont-Mauviel8, J G Guillet3, M Kazatchkine9, J F Delfraissy4, J P Aboulker2, and ANRS 093 Study Group, ANRS, Paris, France These results provide evidence that a sustained control of viremia correlated with enhanced viral-specific cellular responses may be achieved through therapeutic immunization in chronic HIV-1 infection. These effects translated into a significant reduction in exposure to HAART. |
| 134 | IMMUNIZATION OF RHESUS MONKEYS WITH A MULTI-GENE HIV-1 DNA/MVA VACCINE PROVIDES PROTECTION FROM SYSTEMIC INFECTION AFTER REPEATED LOW-DOSE INTRARECTAL SHIV HETEROLOGOUS CHALLENGE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 134) Salvatore Butera1, D Ellenberger1, L Wyatt2, B Li1, S Buge1, I Rodriguez3, C Sariol3, M Martinez3, A Greenberg1, E Kraiselburd3, B Moss2, H Robinson4, J McNicholl1, R Otten1, and T Folks1 These findings provide the first evidence that a multigene HIV-1 DNA/MVA vaccine may successfully prevent transmission in a SHIV-monkey model when the challenge dose more closely mimics that in human sexual transmission. Furthermore, this system provides insight into correlates of protection that may involve subtle aspects of immunity distinct from standard vaccine-elicited T-cell and serologic responses. |
| 135 | SAFETY AND IMMUNOGENICITY OF THE MRK ADENOVIRUS TYPE-5 GAG/POL/NEF HIV-1 (TRIVALENT) VACCINE IN HEALTHY ADULTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 135) Frances Priddy1, D Wright2, J Lalezari3, S Santiago4, R Novak5, S Brown6, M Lally7, M Marmor8, J Kublin9, R Leavitt10, R Isaacs10, D Mehrotra10, J Shiver10, D Brown10, and V520 Protocol 016 Study Group Preliminary safety data suggest the MRKAd5 trivalent vaccine was generally safe and well tolerated at all doses studied. Adverse effects occurred most frequently at the 1 x 1011 viral particle dose. Preliminary immunogenicity data suggest that the MRKAd5 trivalent vaccine was immunogenic eliciting responses against the 3 antigens included in the vaccine. |
| 136LB | CHEMOPROPHYLAXIS WITH ORAL TENOFOVIR DISOPROXIL FUMARATE (TDF) DELAYS BUT DOES NOT PREVENT INFECTION IN RHESUS MACAQUES GIVEN REPEATED RECTAL CHALLENGES OF SHIV Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 136LB) Shambavi Subbarao, R Otten, A Ramos, E Jackson, D Adams, C Kim, S Bashirian, J Johnson, M Monsour, R Janssen, L Paxton, A Greenberg, and T Folks This is the first application of a repeat-rectal exposure macaque-model to evaluate chemoprophylaxis as a method of preventing retroviral infection. In this study, chemoprophylaxis with oral TDF delayed, but ultimately did not prevent infection via rectal exposure with virus levels similar to levels in human semen during an acute infection. |
| 137 | PRE-EXPOSURE PROPHYLAXIS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 137) Robert M Grant Pre-exposure prophylaxis (PrEP) involves regular dosing of antiviral agents among individuals with recurring exposures, in contrast to dosing that is triggered by specific contact episodes (PEP). Regular dosing allows for drug levels to be present at the time of exposure, and does not require that individuals recognize the risk of every contact. |
| Session 35—Oral Abstracts Infectious Complications: Prevention and Treatment |
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| 138 | ACUTE INVASIVE BACTERIAL INFECTIONS AND THE NATURAL HISTORY OF HIV-1 DISEASE IN UGANDA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 138) Edward N Janoff, C Gilks, D Nelson, J Nakiyingi, L Awoyinka, E Lugada, J Whitworth, H Rubins, and N French The development of invasive bacterial infections is associated with increased long-term mortality among HIV-infected patients in Uganda. However, both S. pneumoniae and Salmonella occur among a relatively more advanced subset of HIV-infected patients in Uganda with lower CD4+ T cells and higher HIV RNA than among non-case controls. Moreover, although the incidence of these infections is associated with more advanced disease, no persistent changes in either CD4+ T cells or HIV RNA are directly related to the acute infection. Thus, acute invasive bacterial infections may reflect more advanced HIV disease, but these infections do not appear to appreciably drive the disease progression. |
| 139 | THE INCIDENCE OF INVASIVE PNEUMOCOCCAL DISEASE IN THE ERA OF HAART IS THE SAME AS THAT IN THE PRE-HAART ERA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 139) Gregory Lucas, J Keruly, K Gebo, and R Moore IPD is a common event, occurring in approximately 4 per 1000 HIV-infected individuals annually. Despite being correlated with immunologic and virologic factors, there is no evidence that widespread adoption of HAART has led to declines in IPD. In fact, a trend to the contrary was observed, suggesting that modest immune suppression leaves HIV-infected individuals susceptible to IPD. |
| 140 | IMMUNOLOGIC EFFICACY OF A PRIME-BOOST STRATEGY COMBINING A 7-VALENT PNEUMOCOCCAL CONJUGATE VACCINE FOLLOWED BY A 23-VALENT PNEUMOCOCCAL POLYSACCHARIDE VACCINE VS PPV ALONE IN HIV-INFECTED ADULTS WITH 200 TO 500 CD4 CELLS/μL. RESULTS OF THE ANRS 114 STUDY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 140) Philippe Lesprit1, G Pedrono2, J M Molina3, C Goujard4, P M Girard5, N Sarrazin2, C Katlama6, P Yéni7, P Morineau8, B Fritzell9, J F Delfraissy4, G Chčne2, Y Lévy1, and A Study Group10 In a setting of practical care, a PCV prime–PPV boost strategy enhances the frequency, breadth, and magnitude of antibody responses against SPP compared with the currently recommended PPV alone in HIV-infected adults with moderate immunodeficiency. |
| 141 | RANDOMIZED CLINICAL TRIAL OF 6-MONTH VERSUS 9-MONTH ANTI-TUBERCULOSIS TREATMENT IN HIV+ INDIVIDUALS WITH PULMONARY TUBERCULOSIS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 141) Soumya Swaminathan1, S Iliayas1, C Padmapriyadarsini1, S Rajasekaran2, V Mohan1, C Ponnuraja1, P Venkatesan1, R Ramachandran1, C Paramasivan1, S Ramesh Kumar1, P Menon1, M Dilip1, and P Narayanan1 A 6-month regimen of thrice-weekly anti-TB therapy resulted in a high cure rate, similar to the 9-month regimen. Relapse appeared to be similar in the 2 arms; follow-up is ongoing. These results have implications for TB treatment programs in resource-constrained countries. |
| 142 | INCIDENCE OF AND RISK FACTORS FOR CLINICALLY SIGNIFICANT MRSA INFECTION IN A COHORT OF HIV-INFECTED ADULTS: RELATION TO SEVERITY OF HIV DISEASE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 142) Christopher Mathews1, F Torriani1, L Miller2, E Barber1, J Caperna1, S May1, and A McCutchan1 Incidence of initial clinically significant MRSA events increased over 6-fold over a 4-year period. The association between clinically significant MRSA and HIV viral load, and its effect modification by CD4, is previously unreported and suggests a direct effect of HIV on anti-staphylococcal defenses. |
| 143LB | 2 MILLION YEARS OF LIFE SAVED: THE SURVIVAL BENEFITS OF AIDS THERAPY IN THE UNITED STATES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 143LB) Rochelle P. Walensky1,2, A Paltiel3, E Losina4, L Mercincavage4, B Schackman5, P Sax2, M Weinstein6, and K Freedberg6 Progress in HIV care has saved nearly 2 million years of life in the United States since 1989. The per person benefits far exceed those conferred by treatment of other chronic diseases and highlight the importance of HIV diagnosis, linkage to effective care, and continued research in HIV therapeutics. |
| Session 36—Oral Abstracts Viral and Cellular Determinants of Pathogenesis |
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| 146 | CCL3L1 GENE-CONTAINING DUPLICATIONS SIGNIFICANTLY INFLUENCE VERTICAL TRANSMISSION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 146) Andrea Mangano1, E Gonzalez2, H Kulkarni2, H Bolivar2, M Dolan3,4, R Bologna1, L Sen1, and S Ahuja2 Our results demonstrate that variation in CCL3L1 gene copy number is a powerful determinant of susceptibility to HIV-1 infection. |
| 147 | HIV CO-RECEPTOR USAGE DICTATES TARGET-CICS OF CD4+ T-CELL DEPLETION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 147) Siu-hong Ho1, L Shek1, A Gettie1, J Blanchard2, and C Cheng-Mayer1 Our findings firmly establish co-receptor usage as the sole determinant of target-cell and tissue specificity of the virus in vivo, and dictates the dynamics of CD4+ T-cell depletion during HIV infection. Since progressive loss of CD4+ T lymphocytes underlies the development of AIDS in HIV-1- infected individuals, the two isogenic R5- and X4- SHIV clones described here will provide valuable tools to further advance our understanding of the impact of co-receptor usage on AIDS pathogenesis. |
| 148 | CD16+ MONOCYTES TRANSMIT HIV-1 TO CD4+ T CELLS FOLLOWING CELL-TO-CELL CONTACT AND RENDER RESTING T CELLS PERMISSIVE TO PRODUCTIVE INFECTION BY PRODUCING EOTAXIN-2 AND MCP-1 Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 148) Petronela Ancuta and D Gabuzda CD16+ MO transmit HIV virions to activated CD4+ T cells following cell-to-cell contact and render resting T cells permissive to HIV infection by producing eotaxin-2 and MCP-1. Thus, expansion of CD16+ MO in HIV-infected individuals may contribute to HIV pathogenesis by carrying infectious virions into anatomic sites where CD16+ MO are preferentially recruited and producing eotaxin-2 and MCP-1, which activate resting CD4+ T cells and render them permissive to productive HIV infection. |
| 149 | MACROPHAGES DRIVE B LYMPHOCYTE DYSFUNCTION IN HIV-1 INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 149) Simon Swingler, J Zhou, T Greenough, and M Stevenson The production of ferritin by HIV-1 infected macrophages and the novel immunological properties of ferritin offer a greater understanding of the mechanism of B-cell dysfunction. These findings provide additional evidence on the significance of macrophages in HIV infection and further support Nef as a major pathogenesis factor in HIV disease. |
| 150 | VISUALIZING VIRUS CAPTURE AND TRANSMISSION BY DENDRITIC-CELL INTERFERENCE WITH A FUSION INHIBITOR Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 150) Ines Frank1, H Stoessel2, N Romani2, B Crise3, D Morcock3, D Ott3, E Chertova3, J Lifson3, and M Pope1 AT-2 inactivated and ALEXA-labeled viruses represent a unique way to monitor DC-virus interplay and DC-driven virus spread. Being non-infectious, we can selectively explore the contribution of this phase of DC-to-T-cell transfer to virus spread. The complex nature of DC-virus interactions and the partial blocking effects of single inhibitors underscore the need to explore a combination of attachment, fusion, and entry inhibitors to efficiently block virus capture by DC and virus growth in the DC-T-cell milieu. |
| 151LB | POLYMORPHISM IN RHESUS MACAQUE TRIM5 ASSOCIATED WITH AN INNATE SUSCEPTIBILITY TO SIV INFECTION AND DISEASE PROGRESSION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 151LB) Toshiaki Kodama, T Kawahara, B Wahlberg, A Hartman, P Rajakumar, and M Murphy-Corb These results suggest that the polymorphism in rhTRIM5 resulting in a differential expression of wt- and d6-rhTrim5α might be an important host genetic factor determining the innate susceptibility to SIV infection and disease progression. |
| 152 | FUNCTIONAL DIFFERENCES IN DENDRITIC-CELL POPULATIONS PROVIDE CLUES TO THE DETERMINANTS OF DIVERGENT DISEASE OUTCOMES FOLLOWING SIV INFECTION OF NATURAL AND NON-NATURAL HOST SPECIES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 152) Silvija Staprans1, A Barry1, S Klucking1, R Chavan1, K Dalbey1, M Wernett1, H McClure2, G Silvestri1, and M Feinberg1 These findings point to a break in the normal communication between innate and adaptive immune responses following SIV infection of a natural host species. Lack of DC activation and type I IFN production in SIV-infected SM may lead to an anti-inflammatory immune response that protects this host from the bystander damage seen in pathogenic primate lentivirus infections. |
| 153 | EFFECTOR MEMORY CD4+CCR5+ T CELLS ARE MARKEDLY REDUCED IN NORMAL, NON-PROGRESSING PRIMATE HOST SPECIES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 153) Ronald Veazey, P Marx, J Dufour, C Apetrei, A Lackner, and I Pandrea In normal humans, macaques, and all other species tested, effector memory CD4+ T cells comprise a major proportion of the intestinal T-cell pool. In progressing hosts, these cells are selectively depleted in SIV and HIV infection, and turnover of these cells serves as “fuel” for active viral replication. Remarkably, we found that these cells are essentially absent in both uninfected sooty mangabeys and African green monkeys. The striking absence of activated, memory CD4+CCR5+ T cells in their tissues suggests that co-evolution of these natural hosts with SIV over millennia has resulted in the selection of animals that have few intestinal CD4+ T cells (AGM) or that do not express CCR5 on their intestinal CD4+ T cells (SM). Evolutionary pressure from the virus may have changed fundamental aspects of the immune system in these species to evade AIDS |
| 154 | RELATIONSHIP BETWEEN CELLULAR IMMUNE RESPONSES AND VIRAL LOAD IN NATURALLY SIV-INFECTED SOOTY MANGABEYS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 154) Zichun Wang1, B Metcalf1, D Lee2, S Staprans2, H McClure2, and A Kaur1 These data suggest a role for SIV-specific CD8+ T lymphocytes in limiting viral replication during the course of natural SIV infection in SM. |
| 155 | SIV-SPECIFIC CD8 T CELL RESPONSES ARE LIMITED IN THE MAJORITY OF NATURALLY SIV-INFECTED SOOTY MANGABEYS AND THEIR MAGNITUDE DOES NOT CORRELATE WITH PLASMA VIREMIA OR CD4 T CELL COUNT Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 155) Shari Gordon1, P Pagliardini1, B Sumpter1, J Engram1, R Dunham1, D Sodora2, M Feinberg1, S Staprans1, C Ibegbu1, and G Silvestri1 SIV-specific CD8+ T cell-mediated responses are limited (i.e. <0.2% of total CD8+ T cells) in the majority of naturally SIV-infected SMs. When present, their breadth and magnitude do not correlate with either control of viral replication or maintenance of normal CD4+ T cell count. These data indicate that, in SIV-infected SMs, CD8+ T cell mediated cellular immune responses do not play a major role in determining the immunological and clinical course of the infection. |
| 155LB | DISCOVERY OF NEW HUMAN T-LYMPHOTROPIC VIRUSES REVEALS FREQUENT AND ONGOING ZOONOTIC RETROVIRUS INTRODUCTIONS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 155LB) Nathan Wolfe1, W Heneine2, J Carr3, A Garcia2, V Shanmugam2, U Tamoufe4, J Torimiro4, A Prosser2, M LeBreton4, E Mpoudi-Ngole4, F McCutchan3, D Birx3, T Folks2, D Burke1, and W Switzer2 We report that bush-meat hunters in central Africa who are exposed to infected primates are regularly infected with novel HTLV. We discovered at least 6 viruses that had crossed from infected primates, including 2 novel human retrovirus species, HTLV-3 and HTLV-4. The findings demonstrate that cross-species transmission following primate exposure is not the rate-limiting step in retrovirus emergence and suggest that emergence may be predicted by surveillance of human populations exposed to animal reservoirs. |
| Session 37—Oral Abstracts Antiretroviral Therapy: New Agents, New Combinations, and Virologic Responses |
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| 156 | IDENTIFICATION AND BIOCHEMICAL CHARACTERIZATION OF A NEW CLASS OF HIV INHIBITORS: NUCLEOTIDE-COMPETING REVERSE TRANSCRIPTASE INHIBITORS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 156) Dirk Jochmans1, B Kesteleyn1, B Marchand2, M Götte2, T Ivens1, P Dehertogh1, A Peeters1, R Pauwels3, P Wigerinck1, and K Hertogs1 Antiviral assays and biochemical experiments showed that Compound-1 inhibits HIV RT by a mechanism of action that is clearly different from that of current NNRTI and N(t)RTI. The competitive mode of RT inhibition and the effect on enzyme translocation suggest that Compound-1 blocks the DNA polymerization step by binding to the active site of HIV RT and inhibiting nucleotide binding. We therefore propose nucleotide-competing reverse transcriptase inhibitors (NcRTI) as a name for this new class of HIV inhibitors. |
| 157 | CRYSTAL STRUCTURE OF A COMPLEX OF HIV-1 REVERSE TRANSCRIPTASE WITH AN RNASE H INHIBITOR BOUND AT A NOVEL SITE ON THE ENZYME Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 157) Daniel M Himmel1, S Sarafianos1, A Clark, Jr1, M Parniak2, S Hughes3, and E Arnold1 Our results suggest that KMMP05 binding may affect RNase H activity by altering the trajectory of the nucleic acid or enzyme processivity. These studies may help in the design of inhibitors that target a novel binding site and that should have little or no cross-resistance with existing NRTI (nucleoside RT inhibitors) and NNRTI families of antivirals, thus providing options for novel therapeutic strategies in the treatment of AIDS. |
| 158 | THERAPEUTIC INHIBITION OF SIV REPLICATION IN MACAQUES BY GR BLOCKADE AND IMPLICATIONS FOR THERAPY OF HIV-1 Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 158) K Muthumani1, J Boyer1, A Choo1, D Hwang1, K Thieu1, R Parkinson1, E Nietrzeba1, J Kim2, M Lewis3, and David Weiner1 SIV replication in vivo can be targeted by inhibition of the host GR pathway, suggesting important implications for possible treatment of HIV infection by a well-tolerated oral therapeutic. |
| 159 | PA-457, THE FIRST-IN-CLASS MATURATION INHIBITOR, EXHIBITS ANTIVIRAL ACTIVITY FOLLOWING A SINGLE ORAL DOSE IN HIV-1-INFECTED PATIENTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 159) David Martin1, J Jacobson2, D Schurmann3, E Osswald4, J Doto1, C Wild1, and G Allaway1 Single, oral doses of PA-457 demonstrated dose-related antiviral activity and were safe and well tolerated in HIV-infected patients. PA-457 retained activity in 2 patients with extensive resistance mutations. Although longer duration studies are needed to fully establish the potency of this new compound, these initial data support further development of PA-457 as a potential new treatment option for HIV infection. |
| 160 | TMC278: POTENT ANTI-HIV ACTIVITY IN ANTIRETROVIRAL THERAPY-NAĎVE PATIENTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 160) Frank Goebel1, A Yakovlev2, A Pozniak3, E Vinogradova4, P Lewi5, G Boogaerts6, R Hoetelmans6, M P De Béthune6, M Peeters6, and B Woodfall6 TMC278 was highly active as monotherapy for 7 days at all doses studied. TMC278 was safe and well tolerated. A further proof-of-principle study of TMC278 is being carried out in treatment-experienced HIV-1 patients. |
| 161 | ANTIRETROVIRAL EFFECT OF L-000870810, A NOVEL HIV-1 INTEGRASE INHIBITOR, IN HIV-1-INFECTED PATIENTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 161) Susan Little1, G Drusano2, R Schooley3, D Haas4, P Kumar5, S Hammer6, D McMahon7, K Squires8, R Asfour1, D Richman1, J Chen9, A Saah9, R Leavitt9, D Hazuda9, B Y Nguyen9, and Protocol 004 Study Team The potent antiretroviral effect observed after a short period of monotherapy in both ART-experienced and ART-naďve patients provided proof-of-concept for the antiviral activity of ISTI as a new chemotherapeutic class. L-000870810 was generally well-tolerated in patients. |
| 162 | RANDOMIZED, CONTROLLED TRIAL OF LOPINAVIR/RITONAVIR + EFAVIRENZ VS EFAVIRENZ + 2 NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS FOLLOWING A FIRST SUPPRESSIVE 3- OR 4-DRUG REGIMEN IN ADVANCED HIV DISEASE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 162) Margaret Fischl1, R Bassett2, A Collier3, L Mukherjee2, L Demeter4, P Tebas5, M Giuliano6, K Garren7, B Brizz8, J Feinberg9, and Adult AIDS Clinical Trials Group Treatment with EFV+2 NRTI led to lower rates of regimen failure than treatment with LPV/r+EFV, due to decreased toxicity and a trend toward reduced virologic failure. |
| 163 | THE LEVEL OF PERSISTENT VIREMIA LESS THAN 50 COPIES/ML IN PATIENTS ON SUPPRESSIVE ANTIRETROVIRAL THERAPY IS INDEPENDENT OF REGIMEN POTENCY BUT STRONGLY ASSOCIATED WITH PRETREATMENT VIREMIA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 163) Sarah Palmer1, A Wiegand1, F Maldarelli1, J Omachi2, S Brun2, D Kempf2, M King2, J Coffin1, and J Mellors3 The level of persistent viremia below 50 copies/mL was independent of the expected potency of the suppressive regimen (NFV vs LPV/RTV vs NNRTI), but correlated well with baseline viremia. These results imply that persistent viremia on treatment may result from virus production by cells that are infected prior to initiation of therapy. |
| 164LB | EFFICACY OF TMC114/r IN 3-CLASS EXPERIENCED PATIENTS WITH LIMITED TREATMENT OPTIONS: 24-WEEK PLANNED INTERIM ANALYSIS OF 2 96-WEEK MULTINATIONAL DOSE-FINDING TRIALS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 164LB) C Katlama1, D Berger2, N Bellos3, B Grinsztejn4, Richard Haubrich5, T Wilkin6, J M Molina7, C Steinhart8,9, R Pedro10, M P de Béthune11, S De Meyer11, R Hoetelmans11, W Parys12, T Vangeneuden11, and E Lefebvre12 TMC114/r demonstrated unprecedented efficacy in three class-experienced patients with limited treatment options. All TMC114/r doses were generally safe and well tolerated. The recommended dose for further clinical development in treatment-experienced patients is 600/100 mg twice daily. |
| 165LB | VIROLOGICAL AND IMMUNOLOGICAL OUTCOMES AT 3 YEARS FOLLOWING INITIATION OF ART WITH REGIMENS CONTAINING A NNRTI OR PI OR BOTH: THE INITIO TRIAL Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 165LB) D Cooper1 and Patrick Yeni2 Starting ART with a 3-drug/2-class regimen containing EFV is superior to one with NFV (using d4T and ddI as the initial NRTI backbone) for HIV RNA outcomes (but not CD4 response) at 3 years. There is no evidence to support the use of 4-drug/3-class therapy for the initial treatment of HIV infection. |
| Session 42—Oral Abstracts The Evolving HIV Epidemic: Risk Behavior, Incidence, and Prevalence |
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| 166 | THE PREVALENCE OF HIV IN THE UNITED STATES HOUSEHOLD POPULATION: THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEYS, 1988 TO 2002 Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 166) Geraldine McQuillan, B Kottiri, and D Kruszon-Moran HIV seroprevalence in the household population did not significantly change in the 10 years between the 2 surveys, but did significantly increase in the non-Hispanic black population. In the total population, 35% of HIV-infected individuals reported taking ART drugs compared with 18% in the non-Hispanic black population. Since 91% of those who knew their HIV status were being treated, awareness of HIV status continues to be an important component of HIV/AIDS prevention. Data from this representative sample of the U.S. household population demonstrates that racial and ethnic disparities in HIV infection are increasing on national level but since most individuals who knew about their infection were receiving treatment, an increased awareness and availability of HIV testing should help reduce these racial and ethnic disparities. |
| 167 | ESTIMATED NUMBER OF HIV-INFECTED PERSONS ELIGIBLE FOR AND RECEIVING HIV ANTIRETROVIRAL THERAPY, 2003--UNITED STATES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 167) Eyasu Teshale, L Kamimoto, N Harris, J Li, H Wang, and M McKenna Using the largest set of national data available, we estimated that only 55% of eligible PLWHA age 15 to 49 years old are receiving ART in the United States, suggesting a substantial unmet health care need for this service. Validation of these estimates and examination of factors affecting availability, accessibility, and acceptability to ART are needed. The number of PLWHA eligible for and receiving ART can be better estimated when all HIV and AIDS case surveillance jurisdictions are integrated and new population-based clinical surveillance systems are established. |
| 168 | A COMPARISON OF ON-LINE AND OFF-LINE RISK AMONG MEN WHO HAVE SEX WITH MEN Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 168) Mary Ann Chiasson1, S Hirshfield1, M Humberstone1, R Remien2,5, R Wolitski3, and T Wong4 More than 25% of men recruited online in this study had UAI with 1 or more partners in their last encounter. The large number of men on-line and the diversity of their risk and ways of meeting partners show that the Internet provides a unique opportunity for far-reaching behavioral interventions, particularly those that incorporate information about links between UAI and drug use. |
| 169 | BATH-HOUSES, BARS, AND BRIDGES: PATTERNS OF SEXUAL PARTNER RECRUITMENT IN A COHORT OF MSM WITH RECENT HIV INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 169) Simon Frost1, S Cheng1, L Drumright1, A Leigh Brown2, D Richman1,3, S Little1, and P Gorbach4 Many participants reported no recruitment of sex partners over a 3-month period, despite attending many bars and clubs, implying that spread of HIV from these individuals during acute/early infection may be limited. However, many of the participants who reported one or more casual partners either attended bath-houses, or bars or clubs where other individuals who attended bath-houses recruited partners. Work is underway to determine whether clustering of individuals by recruitment venue correlates with clustering of HIV by genetic similarity. |
| 170 | SPATIAL MONITORING OF INCIDENCE: USING HIV BIOMARKERS TO IDENTIFY CLUSTERS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 170) Kristen Hampton1, C Pilcher1, S Fiscus1, E Foust2, W Messer1, M Serre1, J McPherson2, D Williams2, R Ashby2, T Nguyen1, B Stalzer1, J Harris2, A Cachafeiro1, J Eron, Jr1, and P Leone1,2 The STAT system for geomapping makes it possible for North Carolina to passively monitor HIV transmission events and detect localized high transmission areas based on significantly raised incidence. Geomapping is a powerful tool for better understanding transmission dynamics and clustering of HIV infections, and can be used to guide resource allocation at the state level. |
| 171 | HIV INCIDENCE IN BLOOD DONORS IN FRANCE BETWEEN 1992 AND 2003 USING AN IMMUNOASSAY FOR IDENTIFICATION OF RECENT INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 171) Josiane Pillonel1, S Laperche2, S Le Vu1, B Liandier3, and F Barin3 The consistency of the results of the assay for recent infection with the interval between the positive and the last negative donation on one hand, and the similarity of incidence rates with the classical method on the other hand, validate the relevance of the immunoassay for recent HIV infection. This new assay allowed us to estimate the HIV-1 incidence in first time donors showing that incidence is slightly higher in this population than in repeat donors and that it has decreased overtime in both populations. |
| 172 | THE EFFECT OF ART ON CROSS-SECTIONAL INCIDENCE TESTING: THE 2001 JOHNS HOPKINS HOSPITAL EMERGENCY DEPARTMENT SERO-SURVEY AS AN EXAMPLE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 172) Oliver Laeyendecker1, C Henson2, B Horne2, R Rothman2, K Ketlogetwe2, J Shahan2, G Kelen2, and T Quinn1,2 The use of ART in a population significantly affects the capacity of STARHS in determining HIV incidence. Finally, these results suggest that inner city emergency departments provide an opportunity to identify previously unrecognized HIV infection and together with incidence testing allow for real-time monitoring of the epidemic. In addition the emergency department could serve as a venue for disseminating information to at risk individuals. |
| 173 | HIV INFECTION AMONG YOUNG BLACK WOMEN Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 173) Lisa Fitzpatrick1, F Forna1, A Greenberg1, P Leone2, A Adimora2, and E Foust3 HIV infection in black women was correlated with herpes, an ulcerative sexually transmitted disease (STD). Therefore, biomedical research and therapeutic interventions that integrate HIV and STD treatment and prevention are warranted. In addition, socioeconomic determinants of HIV infection highlight the need for a multi-dimensional approach to address HIV transmission in this population. |
| Session 43—Symposium HIV Replication: Co-Factors and Host Restrictions |
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| 174 | TRIM5α: A MEDIATOR OF INNATE INTRACELLULAR IMMUNITY TO RETROVIRUSES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 174) M Stremlau1, B Song1, M Perron1, C Owens1, H Javanbakht1, W Ulm2, R Mulligan2, B Gold3, C O'hUigin3, C Winkler4, M Dean3, and Joseph Sodroski1 Several retroviruses, including human and simian immunodeficiency viruses and N-tropic murine leukemia viruses, encounter early blocks after entering the cells of particular primate species. These blocks are mediated by TRIM5α, which targets the viral capsid. |
| 175 | CYCLOPHILIN AND INNATE RESISTANCE TO HIV-1 Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 175) Jeremy Luban Capsid (CA)-specific restriction factors are determinants of retroviral tropism in mammalian cells. These dominant factors act after viral entry but before integration into the host genome. |
| 176 | HOST FACTORS IN HIV BUDDING Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 176) Heinrich Gottlinger1, B Strack2, A Calistri2, E Popova1, and A Zamborlini2 HIV-1 budding from the plasma membrane requires a membrane fission event to separate the fully assembled viral particle from the host cell. The detachment of the virion is mediated by the p6 region of Gag, which harbors the so-called late assembly domain of HIV-1. |
| 177 | TSG101 AND OTHER CELLULAR CO-FACTORS IN HIV ASSEMBLY AND RELEASE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 177) Carol Carter1, L Ehrlich1, A Goff1, G Medina1, Q Lu2, S Cohen2, and M Powell3 Results suggest that HIV-1 Gag recruits Tsg101 to a distinct subset of vesicles from which the protein is transported to budding sites on the plasma membrane will be discussed. |
| 178 | VPU OVERCOMES A HOST CELL RESTRICTION TO RETROVIRUS ASSEMBLY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 178) V Varthakavi, K Martin, RM Smith, and Paul Spearman Vpu is an accessory protein of HIV-1 that is absent in most simian immunodeficiency viruses (SIVs). Vpu enhances HIV particle assembly or release in a variety of human cells, but exerts no effect on assembly in African green monkey (AGM) cells. We carried out experiments to determine whether a Vpu-like “positive” factor exists in AGM cells, or conversely if a restrictive factor is present in human cells. |
| Session 44—Symposium Key Topics in Antiretroviral Therapy |
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| 179 | SCIENTIFIC RATIONALE FOR ANTIRETROVIRAL THERAPY IN 2005 Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 179) Robert F Siliciano This talk will discuss key scientific principles underlying antiretroviral therapy, focusing on the unique way in which HIV evolves in vivo. In viremic patients, there are two important populations of virus: a quantitatively dominant, rapidly evolving population that is replicating in activated CD4+ T cells and macrophages, and small stable populations of viruses that persist in cellular reservoirs. |
| 180 | HIV DRUG RESISTANCE: SMALL CHANGES, BIG DIFFERENCES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 180) Francois Clavel HIV resistance is the near inevitable consequence of failure of antiretroviral drugs to fully suppress viral replication in treated patients. Once resistance has emerged, it is usually irreversible, and extensive cross-resistance within each class of antiretroviral agents can severely compromise the further efficacy of HAART regimens. Therefore, any attempt to control virus replication in patients harboring resistant HIV variants should combine drugs that can be proved to retain maximal antiviral activity. |
| 181 | SIMPLIFIED MAINTENANCE THERAPY REVISITED Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 181) Diane Havlir “Induction Maintenance” is a treatment strategy where an intensive induction regimen is simplified to a less potent and more tolerable maintenance regimen. The goal of the strategy is to reduce drug toxicity, drug interactions, and cost and pill burden while maintaining control of viral replication. |
| 182 | CHALLENGES IN THE TREATMENT OF TWO INFECTIONS: HIV AND TUBERCULOSIS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 182) William Burman Tuberculosis (TB) is the single most common opportunistic infection among HIV-infected persons worldwide, and persons with HIV-related TB have a substantial risk of death and other opportunistic infections during the 6-9 month period of TB treatment. Therefore, antiretroviral therapy should be a key intervention among persons with HIV-related TB. However, treatment of two infections at the same time is challenging. |
| Session 50—Poster Abstracts Viral Replication: Early Events, Fusion, and Tropism |
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| 200 | CXCR4-TROPIC HIV-1 ENVELOPE GLYCOPROTEIN FUNCTIONS AS A VIRAL CHEMOKINE IN UNSTIMULATED PRIMARY CD4+ T LYMPHOCYTES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 200) K Balabanian, J Harriague, C Decrion, B Lagane, S Shorte, F Baleux, J L Virelizier, F Arenzana-Seisdedos, and Lisa Chakrabarti Gp120, in monomeric as well as oligomeric, virion-associated form, elicited a complex cellular response that mimicked the effects of a chemokine. HIV-1 has therefore the capacity to dysregulate the vast CD4+ T-cell population that expresses CXCR4. In addition, HIV-1 may exploit its chemotactic properties to retain potential target cells and locally perturb their cytoskeleton, thereby facilitating viral transmission. |
| 201 | CRYO-ELECTRON MICROSCOPY OF HIV-1 AND SIV SURFACES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 201) Ping Zhu1, E Chertova2, J Bess2, J Liu1, K Taylor1, J Lifson2, L Arthur2, and K Roux1 Cryo-EM can be used to visualize internal and external structural details on AIDS virions. The data suggest that there is an interaction between the cytoplasmic tail of TM and the viral matrix. |
| 202 | HIV-1 EXPLOITS HOST SULFATIONS TO FACILITATE ITS ENTRY INTO HUMAN CELLS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 202) M Bobardt, A Parseval, J Elder, and Philippe Gallay HIV-1 uses a single highly conserved arginine in gp120 to bind both syndecans and CCR5 via common sulfated motifs. Thus, HIV-1 exploits host sulfations to ensure successful infection of cells that express low CD4 levels. |
| 203 | RESTRICTED VARIABLE RESIDUES IN THE STEM OF HIV-1 V3 LOOP REGULATE MOLECULAR ANATOMY OF CCR5 UTILIZATION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 203) Q Hu1, K Napier2, J Trent2, Z Wang3, S Taylor4, G Griffin1, S Peiper3, and R Shattock1 These findings indicate that Asp or Asn at position 324 of the V3 stem stabilizes the conformation of V3 loop and hence influences the intensities of interaction between CD4-activated gp120 and CCR5, which results in viral entry. Our study illustrates the power of characterizing co-receptor function with chimeras and provides insight into the role of the V3 loop in the association of gp120 with the CCR5 co-receptor. |
| 205 | PREDICTED CO-RECEPTOR USAGE OF HIV-1 IN LOW-LEVEL VIREMIAS DURING HAART Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 205) Nicole Tobin, M Jensen, G Learn, J Mullins, and L Frenkel Viral co-receptor use by low-level viremia sequences appears to correspond with the mechanism causing the low-level viremia: low-level viremia from subjects with viral replication during HAART predominately used the CXCR4 co-receptor, and low-level viremia from expression of archived virus used the CCR5 co-receptor. These data further support our hypothesis that these 2 distinct phenomena cause low-level viremia. Further studies of larger populations are warranted to determine whether low-level viremia co-receptor use can distinguish between ongoing viral replication vs expression of archived virus, due to differences in their clinical consequences. |
| 206 | A SINGLE AMINO ACID SUBSTITUTION IN THE HIV-1 GP41 CYTOPLASMIC DOMAIN AFFECTS ASSEMBLY OF A PATIENT-DERIVED ENVELOPE GLYCOPROTEIN Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 206) Jayanta Bhattacharya, J M Jacque, and P Clapham These results indicate that R787 in the gp41 cytoplasmic domain is an important determinant in envelope assembly but can be complemented by unknown determinant/s present in the NL43 envelope. |
| 207 | GENERATION OF A TEMPERATURE ARRESTED INTERMEDIATE OF HIV VIRUS-CELL FUSION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 207) Hamani Henderson and T Hope These studies demonstrate that a temperature arrested state can be created for virus–cell fusion, which can be used as a valuable tool to synchronize entry and study HIV fusion. The use of various inhibitors gives insight to how far virus-cell fusion has proceeded during temperature arrested state. Successful inhibition by sCD4 before, but not after temperature arrested state implies that engagement between gp120 and cell surface receptor, CD4 had already taken place during temperature arrested state. Further, the time required to become resistant to AMD 3100 is less after temperature arrested state than before. However, complete inhibition by AMD 3100 suggests that CXCR4 involving steps in the fusion process have not yet been fulfilled. These data imply that temperature arrested state provides a kinetic predisposition for engagement of CXCR4 by virion-associated gp120. |
| 208 | CHARACTERIZATION OF HIV RECEPTOR AND CO-RECEPTOR DYNAMICS USING PHOTOACTIVATABLE GFP Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 208) Andrea D Anderson, C Steffens, and T Hope CD4, CXCR4, and CCR5 fluorescently labeled fusion proteins function and localize normally making them an effective way to study the dynamics of these proteins. In addition, preliminary studies with our PA-GFP constructs suggest differences in the rate and degree of diffusion between the 3 proteins and that CXCR4 may contain an immobile phase similar to that previously described for CD4. |
| 209 | SCD4 INDUCES EXPOSURE OF THE HIV-1 GP41 PRE-HAIRPIN INTERMEDIATE IN THE ABSENCE OF GP120 DISSOCIATION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12:.(abstract no. 209) Nicole Kilgore, K Salzwedel, M Reddick, and C Wild These results extend our previous work demonstrating that sCD4 is sufficient to induce exposure of a gp41 pre-hairpin fusion intermediate. Specifically, we establish that the Env conformational changes leading to the exposure of this gp41 fusion intermediate are due solely to sCD4-induced changes in Env conformation and are not the result of gp120 shedding. These results strengthen the support for a model in which CD4, alone, is sufficient to induce formation of the gp41 pre-hairpin intermediate. |
| 210 | SELECTION OF PEPTIDES THAT INTERFERE WITH HIV-1 INFECTION AND ISOLATION OF HOST CELLULAR FACTORS INVOLVED Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 210) Roland Wolkowicz, G Jager, and G Nolan We rescued several peptides that interfere with viral infection. One of the peptides binds the JAB-1/subunit 3 of the signalosome. The use of random peptide libraries can be efficiently applied in the search for novel molecules with pharmacologic properties against HIV-1 and other infectious pathogens. |
| 211 | REPLICATION COMPETENT VARIANTS OF HIV-2 WITH DELETIONS OF THE V1/V2 AND V3 HYPERVARIABLE LOOPS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 211) George Lin1,2, A Bertolotti-Ciarlet2, M Biscone2, B Haggarty2, J Romano2, J Reeves2, J Miamidian2, R Doms2, and J Hoxie2 Our findings represent a proof of concept that replication-competent HIV lacking V1/V2 and V3 can be derived. Because variable loops are implicated in protecting gp120 core domains from antibody responses, loop-deleted HIV may be useful for producing novel immunogens that can focus humoral responses to conserved and/or cryptic epitopes on the Env trimer. Efforts to extend this work to HIV-1 are underway. |
| 212 | STOICHIOMETRIC REQUIREMENTS OF ENVELOPE GLYCOPROTEINS IN THE ENTRY OF HIV-I, AMPHOTROPIC MURINE LEUKEMIA VIRUS, AND INFLUENZA A VIRUS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 212) Xinzhen Yang, S Kurteva, X Ren, S Lee, and J Sodroski Thus, entry of distinct viruses requires markedly different degrees of cooperation among the envelope spikes, which has important implications in viral replication and pathogenesis. |
| 213 | PREFERENTIAL USE OF CXCR4 BY R5X4 HIV-1 ISOLATES FOR INFECTION OF PRIMARY LYMPHOCYTES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 213) Yanjie Yi, F Shaheen, and R Collman These results indicate that co-receptor phenotype in transformed cells does not necessarily predict utilization in primary cells, and many or most strains characterized as R5X4 use CXCR4 only to infect primary lymphocytes. Less efficient interaction between R5X4 strains and CCR5 may be responsible for the inability to use CCR5 on lymphocytes, which express relative low CCR5 levels. These results have implications for the evolution from R5 to R5X4 during disease progression, and for the use of chemokine receptor antagonists as antiretroviral therapeutics. Furthermore, since isolates that acquire CXCR4 utilization retain the ability to use CCR5 on macrophages despite their inability to use CCR5 on lymphocytes, these results also raise the possibility that a CCR5-mediated macrophage reservoir is required for sustained infection in vivo. |
| 214 | HIV-1 ENVELOPE GP120 DETERMINANTS OF CXCR4-MEDIATED INFECTION OF MACROPHAGES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 214) G Ghaffari1, D Tuttle1, Joshua Bunger2, J Sleasman3, and M Goodenow3 Our results suggest that cell-type-specific regulation of viral entry is comprised of a discontinuous interaction of V1, V2, and V3 hypervariable loops and elements of CD4-binding. Determinants of receptor affinity are significant for development of new treatment strategies, including therapeutic vaccines that control replication of D-X4 viruses to prevent evolution of more pathogenic D-X4 viruses and delay disease progression. |
| 215 | A RELIABLE CO-RECEPTOR USAGE PREDICTOR FOR HIV-1 SUBTYPE C BASED ON ENV V3 SEQUENCE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 215) Mia Coetzer1, M Jensen2, A van't Wout3, L Morris1, and J Mullins3 We derived a C-specific phenotype predictor that performs nearly as well on C V3 loops as do existing B-specific methods on B V3 loops, and can thus be applied to characterize C V3 sequence of unknown co-receptor use. V3-HTA could provide an inexpensive method for scoring large numbers of subtype C V3 samples. |
| 216 | PHENOTYPIC CHARACTERIZATION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE I (HIV-1) ENVELOPES DERIVED FROM KIDNEY AND BLOOD OF PATIENTS WITH RENAL DISEASES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 216) B Zerhouni-Layachi, P Klotman, and Mary E Klotman Our preliminary results demonstrated that the patterns of co-receptor usage were heterogeneous, with no clear distinctions between kidney and blood env clones to account for renal compartmentalization. The evolution of distinct quasi-species within the kidney compartment is not manifested by a distinct co-receptor usage pattern. |
| 217 | A HIV-1 MINIMAL GAG PROTEIN IS SUPERIOR TO NC AT IN VITRO tRNALys3 ANNEALING AND EXHIBITS MULTIMERIZATION-INDUCED INHIBITION OF REVERSE TRANSCRIPTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 217) Ariel Roldan, B Spira, O Warren, R Russell, C Liang, and M Wainberg These results strongly suggest that nucleocapsid in the context of the precursor has greater annealing properties than nucleocapsid alone, and that the initial stages of reverse transcription may be regulated by the multimerization ability of Pr55Gag polyprotein at times prior to cleavage of nucleocapsid. |
| 218 | INTRACYTOPLASMIC MATURATION OF THE HIV-1 PRE-INTEGRATION COMPLEXES DETERMINES THEIR CAPACITY TO INTEGRATE INTO CHROMATIN Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 218) Sergey Iordanskiy, R Berro, F Kashanchi, and M Bukrinsky Most PIC complete reverse transcription in the cytoplasm and then transport to the nucleus, but some, especially early after infection, get into the nucleus before completing DNA synthesis. Since cPIC and nPIC reveal similar protein composition reverse transcription may continue in the nuclear compartment. However, completion of reverse transcription in nPIC does not increase their integration capacity. This result suggests that nPIC containing RT and immature DNA are defective for integration. |
| 219 | SPECIFIC INTERSUBUNIT TRP-MOTIF INTERACTIONS ARE CRITICAL FOR HIV-1 RT FUNCTION IN VIVO Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 219) Alok Mulky1, S Sarafianos2, Y Jia1, E Arnold2, and J Kappes1 Detailed examination of our results, reverse transcriptase crystal structure, and previous reports on the Trp-motif suggests that mutating p66W401/p51W401 causes repositioning of the αL-β20 loop in p66 and disruption of specific intersubunit interactions, resulting in a loss of reverse transcriptase dimerization and virus infectivity. This analysis of the reverse transcriptase connection subdomain identifies a putative “hot spot” for p51-p66 interaction in the Trp-motif and provides new insights relevant to targeted drug design. |
| Session 51—Poster Abstracts (and Session 25—Poster Discussion) The Role of LEDGF in Viral Replication |
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| 220 | LEDGF/P75 IS A CO-FACTOR OF LENTIVIRAL INTEGRASES AND PLAYS A ROLE IN HIV REPLICATION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 220) Linos Vandekerckhove1, F Christ1, K Busschots1, J Vercammen2, S Emiliani3, R Benarous3, M Witvrouw1, Y Engelborgs2, and Z Debyser1 LEDGF/p75 is the first cellular co-factor of HIV integrase that has been unambiguously shown to be important for HIV replication. LEDGF/p75 seems to play a role in the nuclear trapping of integrase and its tethering to the chromosomal DNA. This mechanism is apparently specific for lentiviridae. |
| 221 | LEDGF/P75 PREVENTS PROTEASOMAL DEGRADATION OF HIV-1 INTEGRASE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 221) Manuel Llano, S Delgado, M Vanegas, and E Poeschla Here we identify a second function for the LEDGF/p75-integrase interaction. LEDGF/p75 protects HIV integrase from proteasome degradation. Protection requires integrase-LEDGF/p75 interaction and it is independent of the subcellular localization of this protein complex. We postulated that LEDGF/p75 prevents the recognition of HIV integrase by an E3 ligase. |
| 222 | IDENTIFICATION OF THE LEDGF/P75 HIV-1 INTEGRASE-INTERACTION DOMAIN AND NLS REVEALS NLS-INDEPENDENT CHROMATIN TETHERING Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 222) Maria Vanegas, M Llano, S Delgado, D Thompson, M Peretz, and E Poeschla LEDGF/p75 is a multi-domain adaptor protein that interacts with the nuclear import apparatus, lentiviral integrase proteins, and chromatin by means of a nuclear localization signal, an integrase-binding domain, and additional chromatin-interacting domains. |
| 223 | RNA INTERFERENCE AS A VALIDATION TOOL FOR LEDGF/P75 AND OTHER POTENTIAL CO-FACTORS FOR HIV-1 REPLICATION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 223) Frauke Christ, L Vandekerckhove, M Witvrouw, and Z Debyser RNAi is a powerful tool to validate potential cellular co-factors of HIV-1 replication. Both siRNA and shRNA proved valuable in the validation process of LEDGF/p75. Inhibition of HIV-1 replication correlated with the level of gene silencing. Although a more profound gene silencing was obtained with siRNA, a significantly lower degree of cellular toxicity was observed with shRNA. This may be related to the lower extent of gene silencing, to the absence of unspecific RNA-induced cellular response, or to adaptation during selection. |
| 224 | NEITHER IMPORTIN 7 NOR LEDGFP75 CONTROLS HIV RT-COMPLEX NUCLEAR IMPORT IN MACROPHAGES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 224) Steven Zielske and M Stevenson Using primary macrophages as biologically relevant targets of HIV and infection, and under a natural infection process, we found no evidence to support IPO7 or LEDGFp75 as mediators of RT complex nuclear import. Neither did loss of IPO7 impair infection efficiency. |
| 225 | GENES REMAIN FAVORED SITES FOR HIV-1 INTEGRATION IN CELLS REDUCED FOR INTEGRASE-BINDING PROTEINS P75/LEDGF AND HRP-2 Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 225) Nicholas Vandegraaff, E Devroe, P Silver, and A Engelman HIV infection appears unaffected under p75/HRP-2 knock-down conditions generated by siRNA transfection. |
| 226 | STRUCTURE ANALYSIS OF THE INTEGRASE-BINDING DOMAIN IN LEDGF/P75 Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 226) Peter Cherepanov1,3, Z Y Sun2, G Wagner2, and A Engelman1,3 The LEDGF/p75 integrase-binding domain is comprised of 5 α-helices folded into a compact right-handed bundle. Results of our mutagenesis scan and in vitro binding assays indicate residues 363-369 forming the loop between the first and the second α-helices of the integrase-binding domain are involved in the interaction with HIV-1 integrase. We confirmed that V165A integrase mutant is defective for binding to LEDGF/p75 and identified several other class II HIV-1 integrase mutants with greatly reduced affinity for this human protein. |
| 227 | LEDGF/P75 IS INVOLVED IN TARGETING OF HIV-1 INTEGRASE TO CHROMOSOMES, INTEGRATION, AND VIRAL REPLICATION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 227) Richard Benarous1, B Van Maele2, A Mousnier3, M Maroun1, L Vandekerckhove2, K Busschots2, M Witvrouw2, J C Rain4, C Dargemont5, Z Debyser2, and S Emiliani1 Altogether, these results indicate that p75 is a major cellular co-factor involved in integration and replication of HIV-1. From these experiments, we can conclude that p75 is probably not directly responsible for the active nuclear import of integrase, but rather targets integrase to the chromosome, thereby influencing the retention of integrase in the nucleus. Interaction of integrase with p75 could play a role in the selection of target sites for integration of HIV-1. |
| Session 52—Poster Abstracts Cellular Co-Factors |
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| 228 | SELECTION OF REPLICATION-COMPETENT VIRUSES THAT INCORPORATE A POTENT ANTIGENIC OR BIOCHEMICAL TAG: TOOLS FOR THE RECOVERY AND IDENTIFICATION OF CELLULAR PROTEINS THAT INTERACT WITH HIV-1 DURING PRODUCTIVE INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 228) Yang Luo1, M Topper2, and M Muesing2 Using our panel of independently tagged, replication-competent derivatives, we seek to recover host proteins that interact specifically with the virus as it progresses through its natural life cycle. Mass spectrometry techniques are in progress to determine the identity of host proteins and their complexes captured via their interaction with the targeted viral protein. |
| 229 | VIRAL AND HOST MICRO-RNA(MIR) ARE UP-REGULATED DURING HIV INFECTION--CENTRAL ROLE OF MIR IN CONTROL OF THE INFECTION? Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 229) Zvi Bentwich HIV infection is associated with up-regulation of several host MIR and appearance of virally encoded MIR. At least some of the host and the virally encoded MIR may have a direct effect on viral replication and latency. Control of MIR expression or its modulation offers a novel approach for therapy of HIV infection. The changed expression of host MIR with HIV infection, may also lend itself to new therapies affecting the host response and susceptibility to HIV infection. |
| 230 | tRNA-LIKE MOLECULES ARE INVOLVED IN NUCLEAR IMPORT OF HIV-1 INTRACELLULAR REVERSE TRANSCRIPTION COMPLEXES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 230) L Zaitseva, L Maluish, R Myers, and Ariberto Fassati These results indicate that tRNA-like molecules may be involved in HIV-1 RTC nuclear import and may represent a new class of cellular ribonucleoproteins. |
| Session 53—Poster Abstracts Host-Cell Restriction Factors: Vif, APOBEC, TRIM5 and Cyclophilin |
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| 231 | MODULATION OF TRIM5α-MEDIATED RESTRICTION ACTIVITY IN PRIMATE CELL LINES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 231) Sarah Sebastian, L Berthoux, and J Luban CypA was found to be a necessary co-factor for TRIM5α-mediated restriction of HIV-1 in Old World monkeys. CypA effects on HIV-1 replication are cell-type specific. Restriction of HIV-1 and N-MLV in Old World monkeys was shown to be counteracted by mitochondria-targeting agents. |
| 232 | TARGET CELL CYCLOPHILIN A MODULATES HIV-1 INFECTIVITY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 232) Elena Sokolskaja, D Sayah, and J Luban Our results clearly demonstrate that target cell CypA, and not producer cell CypA, is important for HIV-1 CA-mediated function. Inhibition of HIV-1 infectivity resulting from virion production in the presence of CsA occurs independently of the CA-CypA interaction. Furthermore, producer cell CypA is not required for virion infectivity, as virions produced from CypA KD cells are as infectious as virions produced from control cells. We also show that cell line–specific effects of CsA on the replication of HIV-1 CA variants are determined by the target cell. These CsA phenotypes of HIV-1 CA variants result from effects of the drug on target cell CypA. |
| 233 | A NATURALLY OCCURRING CAPSID MOTIF GOVERNS HIV-1 DEFENSE AGAINST INNATE PRIMATE RESTRICTIONS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 233) U Chatterji1, M Bobardt1, R Ptak2, L Pallansch2, P Ward2, M Jones2, C Stoddart3, A Saphire1, P Scalfaro4, J M Dumont4, K Besseghir4, B Rosenwirth5, and Philippe Gallay1 We found that HIV-1 exploits at least 2 strategies to escape restrictions in human cells. One defensive strategy consists of the recruitment of CypA onto its viral capsid core that is thought to protect the core from attack by restriction factors. The second defensive strategy relies on the preexistence of a capsid motif, which renders the viral capsid core resistant or invisible to restriction factors. In contrast to the CypA-mediated defense strategy above, this strategy does not rely on CypA-capsid interactions, suggesting that HIV-1 exploits CypA-dependent and -independent defensive strategies to guarantee successful colonization of primates. |
| 234 | CELL BIOLOGY OF TRIM5α Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 234) Xiaolu Wu, E Campbell, and T Hope Trim5α continuously exchanges between the cytoplasmic bodies and a soluble form in the cytoplasm. This demonstrates that cytoplasmic bodies are dynamic in nature rather than protein aggregates or inclusion bodies that represent dead-end static structures. The unique structure and highly dynamic property of cytoplasmic bodies may provide valuable information to illuminate the mechanism of Trim5α function. |
| 235 | HIJACKING CULLIN5-ELONGINB/C E3 LIGASE BY ADENOVIRUS E4ORF6 AND LENTIVIRAL VIF THROUGH VIRAL-SPECIFIC BC BOXES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 235) K Luo1, Elana Ehrlich2, Z Xiao1, Y Yu2, B Liu2, G Ketner2, and X F Yu2 These viral-specific BC-box motifs are highly divergent from the cellular SOCS boxes. Therefore, lentiviral Vif proteins and adenovirus E4orf6 represent novel families of viral BC-box adaptor proteins. The cellular targets of Cul5-containing E3 ligases remain elusive. The identification of these novel BC-box motifs that recruit the Cul5 complex may facilitate the identification of additional adaptor proteins and shed light on the cellular function of Cul5-containing E3 ligase. |
| 236 | APOBEC-3C INDUCES NON-LETHAL HYPERMUTATION IN HIV-1: IMPLICATIONS FOR VIRAL EVOLUTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 236) Khaoula Bourara1, T Liegler1, R Hance1, J Kropp1, and R Grant2 h3C is necessary and sufficient for hypermutation of a patient-derived HIV-1 infectious molecular clone. In contrast with h3G, the action of h3C is non-lethal and is not suppressed by Vif, although there appear to be other viral determinants that modify h3C action. RNAi inhibition of h3C decreases viral mutation in cell culture. Inhibition of h3C may represent a novel strategy for delaying viral escape from immune or antiretroviral drug inhibition. |
| 237 | INHIBITION OF HUMAN T-CELL LEUKEMIA VIRUS TYPE 1 BY APOBEC3G Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 237) Amane Sasada1, A Takaori-Kondo1, K Shirakawa1, M Kobayashi1, A Abudu1, M Hishizawa1, K Imada1, Y Tanaka2, and T Uchiyama1 APOBEC3G showed an antiviral activity on HTLV-1 without exerting a cytidine deaminase activity. Our result suggests that APOBEC3G might act on HTLV-1 and other retroviruses through different mechanisms. Our finding also indicates that innate APOBEC3G in HTLV-1 contributes to the low infectivity of the virus. |
| 238 | UBIQUITINATION OF APOBEC3G BY AN HIV-1 VIF-CULLIN5-ELONGINS B/C COMPLEX Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 238) Akifumi Takaori-Kondo1, M Kobayashi1, Y Miyauchi2, K Iwai2, and T Uchiyama1 HIV-1 Vif could form a Vif-Cul5-Elo B/C complex and this complex acts as E3 ligase to conjugate ubiquitins to APOBEC3G. This also suggests that this complex is sufficient for the ubiquitination of APOBEC3G in vitro. |
| 239 | APOBEC3B AND APOBEC3C ARE POTENT INHIBITORS OF SIV BUT NOT HIV-1 Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 239) Qin Yu1, D Chen1, R König1, R Mariani1, D Unutmaz2, and N Landau1 APOBEC3B and APOBEC3C are potent inhibitors of SIV and are efficiently encapsidated by HIV-1 and SIV. These findings raise the possibility that the different APOBEC3 family members neutralize specific lentiviruses. |
| 240 | DIFFERENTIAL APOBEC3G/3F NEUTRALIZATION ACTIVITIES OF VIF IN VIVO Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 240) Viviana Simon, V Zennou, D Murray, Y Huang, D Ho, and P Bieniasz Vif variants that do not neutralize APOBEC3G or APOBEC3F activity can be found rather frequently in vivo. Sporadic and selective inactivation of Vif’s anti-cytidine deaminase activities may result in selective APOBEC3-driven mutagenesis and thereby exert a major effect on viral evolution in HIV-1-infected individuals. |
| 241 | SEVERAL HUMAN APOBEC3 PROTEINS ARE POTENT CELLULAR INHIBITORS OF HIV-1 Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 241) Brian Doehle1, A Schaefer2, H Wiegand2, and B Cullen1,3,4 These data suggest that activation of the endogenous h3B gene could provide protection from HIV-1 in vivo. However, other than in a few highly differentiated cell lines, we have not observed significant expression of h3B mRNA, including in lymphoid tissues where both h3F and h3G are extensively co-expressed. |
| 242 | ANALYSIS OF HIV-1 HYPERMUTATION AND ITS RELATIONSHIP WITH APOBEC3G AND VIF GENETIC VARIATION IN VIVO Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 242) Simon Mallal, C Pace, D Nolan, J Keller, C Moore, F Carvalho, A Patterson, K Sutton, and S Gaudieri This in vivo study demonstrates that hypermutation is not infrequent at a population level and is associated with lower pretreatment viral load, in keeping with a host antiviral effect potentially mediated by APOBEC3G. |
| 243 | EXPRESSION OF APOBEC3G IN HUMAN CD4+ LYMPHOCYTES IN VIVO Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 243) MariaPia De Pasquale, T Allos, L Sutton, T Gebretsadik, N Madison, M Vetter, and R D'Aquila APOBEC3G RNA levels in primary CD4 lymphocytes vary 6.6 -fold across different humans in vivo, and expression levels are relatively stable over time within an individual. The observed stable inter-individual variation of APOBEC3G RNA across different humans suggests that HIV replication may differ for a given level of vif function. Further study of inter-individual variation in functional APOBEC3G protein, and potential genetic mechanisms underlying this variation, will provide new insight into HIV pathogenesis. |
| 244 | REGULATION OF APOBEC 3F AND HIV-1 VIF BY VIF-CUL5-ELONB/C E3 UBIQUITIN LIGASE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 244) Phuong Sarkis1, B Liu1,2, K Luo1,3, Y Yu1, and X F Yu1,3 Our results indicate that h-A3F may provide a barrier against diverse primate lentiviruses in humans possessing a different determinant of species specificity than that of h-A3G. Furthermore, Cul5-E3 ligase appears to be a common pathway hijacked by HIV-1 vif to defeat both h-A3F and h-A3G. Developing inhibitors to disrupt the interaction between vif and Cul5-E3 ligase could be therapeutically useful, allowing multiple host antiviral factors to suppress HIV-1. |
| 245 | DIFFERENTIAL EXPRESSION OF APOBEC3G IN DISTINCT DENDRITIC CELL POPULATIONS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 245) Harold Oliva1, R Pacheco2, N Climent1, F Borras3, F Garcia1, C Gil1, J Martínez2, J Miró4, R Franco2, N Navaratnam5, J Gatell1, and T Gallart1 We have developed anti-Apo3G mouse monoclonal antibodies that can be used to assess Apo3G protein expression in cells. The reduced expression of Apo3g in immature MDDC compared with cytokine-matured MDDC is compatible with data on the higher vulnerability of immature MDDC to HIV infection than cytokine-matured MDDC. The absence of Apo3G expression in blood plasmocytoid DC and myeloid DC is also consistent with recent data demonstrating the in vitro and in vivo infectivity by HIV-1 of both types of circulating DC. |
| Session 54—Poster Abstracts Viral Replication: Regulation of Viral Gene Expression |
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| 246 | HIGH AFFINITY TAR BINDERS INHIBIT HIV VIRUS REPLICATION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 246) Baode Xie1, M Wainberg1, and A Frankel2 High affinity binders targeted to the TAR sequence of the HIV-1 viral genome are potential inhibitors of HIV-1 gene expression. |
| 247 | PROMOTER-TARGETED dsRNAs INDUCES HIV-1 GENE SILENCING AND DE NOVO CpG METHYLATION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 247) Kazuo Suzuki1, C Suter3, T Shijuuku1, T Fukamachi1, J Zaundeers1, S Ku1, K Cheong1, R Ward1, G Guilemin1, D Martin3, D Cooper2, and A Kelleher2 Transcriptional gene silencing of HIV expression can be achieved via dsRNA targeting the HIV promoter region. The efficacy of silencing depends on the sequences targeted. CpG methylation patterns correlate with the extent of viral suppression. Transcriptional gene silencing induces prolonged HIV-1 suppression compared with dsRNA inducing post-transcriptional gene silencing. |
| 248 | P-TEFb COMPLEXES DURING HIV INFECTION AND CELL DEATH Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 248) Sebastian Biglione, D Price, and W Maury We propose that induction of cell killing by HIV or chemical treatment alters the P-TEFb ratios and generates a modified form of CDK9. Studies are ongoing to characterize this potentially new isoform of CDK9. |
| 249 | REGIONS OF THE HIV-1 REV RESPONSE ELEMENT OUTSIDE THE PRIMARY REV BINDING SITE REGULATE ENV BUT NOT GAG EXPRESSION FROM PROVIRUS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 249) Alex Ward, M L Hammarskjold, and D Rekosh Based on these results, we conclude that RRE stem-loops IV and V are necessary for translation of Env from the bicistronic Vpu/Env when the Vpu open reading frame is intact, but not when it is truncated. |
| 250 | PROTHYMOSIN-α (ProTα) SUPPRESSES HIV-1 GENE TRANSCRIPTION IN PRIMARY MACROPHAGES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 250) Arevik Mosoian1, A Teixeira1, A High2, D Hunt2, and M Klotman1 Our results indicate that ProTα suppresses HIV-1 gene transcription in primary macrophages post-viral integration and contributes to HIV-1 inhibition by CD8+ cell supernatant. |
| 251 | GENOME-WIDE ANALYSIS OF CHROMOSOMAL FEATURES REPRESSING HIV TRANSCRIPTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 251) Mary Lewinski1, D Bisgrove2, P Shinn1, H Chen1, S Hannenhalli3, E Verdin2, C Berry4, J Ecker1, and F Bushman5 These data provide a genome-wide picture of chromosomal features that repress transcription generally. Furthermore, we have identified mechanisms by which integration site can reversibly silence proviruses, suggesting models for transcriptional latency in HIV-infected cells where, upon stimulation of the host cell, previously silent provirus is transcribed to re-seed infection in patients on HAART. |
| 252 | THE γ-c-CYTOKINE-REGULATED TRANSCRIPTION FACTOR, STAT5, ACTIVATES HIV-1 TRANSCRIPTION AND VIRAL REPLICATION IN PRIMARY CD4 T-CELLS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 252) Nithianandan Selliah1, H Kim1, D DeSimone1, M Brunner1, M Zhang1, R Ittenbach1, H Rui2, R Cron1, and T Finkel1 Here, we identify 3 regions in the LTR as close matches to the STAT5 consensus-binding site. We demonstrate that STAT5 binds to the LTR in vivo, activates viral transcription, and induces a permissive state for HIV replication in resting primary CD4 T cells. These data have implications for regulation of latency and therapeutic strategies for control of HIV disease. |
| 253 | PGJ2 ANTAGONIZES NF-κB-INDUCED HIV-1 LONG-TERM REPEAT ACTIVATION IN COLONIC EPITHELIAL CELLS: POTENTIAL APPLICATION IN HIV-1 DISSEMINATION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 253) M Boivert, Salim Bounou, and N Dumais Results suggest that secretion of PGE2 or PGJ2 in the environment of infected colonic epithelial cells could modify the modulation of HIV-1 transcription and alter dissemination of HIV-1 to target cells. |
| 254 | INVOLVEMENT OF BOTH NFAT AND NF-κB IN THE PREFERENTIAL REPLICATION OF HIV-1 IN MEMORY CD4+ T LYMPHOCYTES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 254) Brigitte Audet1, G Robichaud1, D Rothstein2, M Tremblay1, and B Barbeau1 We are thus presenting a mechanism by which the preferential replication occurs. The results obtained strongly suggest that variation in the transcriptional level of HIV-1 is at the basis for the higher viral replication measured in CD4+CD45RO primary T cells. Moreover, both NF-κB and NFAT could be the important factors which would differently modulate HIV-1 LTR activity in these T cell populations. |
| Session 55—Poster Abstracts Viral Replication: Late Events and Assembly |
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| 255 | MUTATIONS IN THE HIV-1-1 FRAMESHIFT SIGNAL: AFFECTING FRAMESHIFT, VIRAL INFECTIVITY, AND REPLICATIONS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 255) D Dulude1, Y Berchiche2,3, L Brakier-Gingras1, and Nikolaus Heveker2,3 The important consequences of minor variations in the frameshift efficiency stress the potential of the frameshift event as a novel target for anti-HIV drugs. |
| 256 | THE DETERMINANTS OF ACTIVITY OF THE HIV-1 MATURATION INHIBITOR PA-457 MAP TO RESIDUES FLANKING THE GAG CA-SP1 CLEAVAGE SITE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 256) F Li1, D Zoumplis1, C Matallana1, C Adamson2, N Kilgore1, M Reddick1, E Freed2, G Allaway1, and Carl Wild1 Taken together, these findings support and extend previous observations that PA-457 is a specific inhibitor of CA-SP1 cleavage and provide strong evidence that this compound specifically targets the CA-SP1 boundary domain of the HIV-1 Gag protein. |
| 257 | A LINK BETWEEN THE EARLY AND THE LATE ENDOSOMAL PATHWAYS DURING HIV-1 ASSEMBLY AND RELEASE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 257) Melissa Batonick1, M Maki2, and M Thali1 We hypothesize that AP-2 serves as a docking point at the plasma membrane for both Gag and AIP1/Alix during HIV-1 assembly and release. |
| 258 | INVOLVEMENT OF THE SP1 REGION IN MEMBRANE-BINDING AND THE SUBSEQUENT ASSEMBLY EVENTS OF HIV-1 GAG Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 258) Xiaofeng Guo, J Hu, B Spira, M Wainberg, and C Liang Our data indicate that the SP1 region plays 2 distinct roles in HIV-1 assembly: targeting Gag to cellular membrane and promoting Gag multimerization on the membrane. Considering the vital role of SP1 in HIV-1 replication, this short motif may represent a potential target for HIV-1 intervention. |
| 259 | GAG VARIABILITY IN DIFFERENT HIV-1 SUBTYPES AND UNDER ANTIRETROVIRAL THERAPY MAY INFLUENCE VIRAL BUDDING Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 259) Africa Holguin, A Alvarez, and V Soriano Amino acid sequences in viral domains involved in the interaction with host cell proteins necessary for HIV budding may vary according to HIV subtype as well as under antiretroviral pressure. The effect of gag variability on budding in different HIV-1 clades needs to be further studied. |
| 260 | TRANSMISSION ELECTRON MICROSCOPY ANALYSIS OF ANNEXIN 2-DEPLETED MDM REVEALS INHIBITION OF HIV ASSEMBLY AND MATURATION IN INTERNAL VESICLES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 260) Andrew Albright, R Vos, A Varela-Rohena, E Ryzhova, and F Gonzalez-Scarano The reduction of Anx 2 protein inhibited HIV maturation in internal vesicles in MDM, which supports our hypothesis that binding of p55Gag to Anx 2 is involved in directing viral assembly and budding to the endosomal membranes in MDM, and that reduction of Anx 2 leads to decreased production of mature HIV particles because this novel HIV maturation pathway has been disrupted. |
| 261 | HIV-1 EGRESS IS GATED THROUGH DISCRETE CD63-ENRICHED MICRODOMAINS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 261) Sascha Nydegger1, M Foti2, A Derdowski3, P Spearman3, D Ott4, and M Thali1 Utilizing evanescent wave fluorescent microscopy, we are currently investigating the dynamics of formation and turnover of the CD63-enriched microdomains. Because CD63 is a resident of late endosomes/multivesicular bodies, we are also analyzing whether these domains are derivatives of the limiting membrane of that compartment which have been recruited to the cell cortex by focal exocytosis or, alternatively, whether the domains accumulate nascent CD63 that trafficks to late endosomes via the plasma membrane. |
| 262 | "CODON VOLATILITY" DOES NOT RELIABLY MEASURE SELECTIVE PRESSURE ON HIV GENES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 262) Satish Pillai, S Kosakovsky-Pond, C Woelk, D Richman, and D Smith Determining which genes and which sites within genes are under the greatest or least selective pressure will be important in rational vaccine design for HIV. Several methods for measuring selection are available; each approach has its strengths and limitations. |
| Session 56—Poster Abstracts Viral Accessory Genes |
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| 263 | NOVEL CELLULAR SIGNALING PATHWAYS MEDIATING CELL CYCLE ARREST BY HIV-1 VPR Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 263) Naoto Yoshizuka and S Zeichner Exogenous complementation of MEK2 abolished the G2 cell cycle arrest induced by Vpr protein, suggesting that vpr targets the MEK2-ERK pathway, modulates the activities of several mitogen-activated protein kinases, and causes G2 cell cycle arrest by integrating stress response and cell cycle checkpoint pathways. These pathways constitute novel signaling cascades mediating G2 cell cycle arrest induced by vpr. As such, they may play an important role in HIV-1 pathogenesis and may represent new antiretroviral therapeutic targets. |
| 264 | STRUCTURE/FUNCTION MAPPING OF HIV-2 VPX BY INSERTIONAL MUTAGENESIS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 264) Lisa Mahnke, M Belshan, N Campbell, and L Ratner In conclusion, we have begun to map structural domains of Vpx by modeling and insertional mutagenesis, while simultaneously tagging the protein, in an effort to understand the role of Vpx in nuclear targeting. |
| 265 | VIF REGULATES THE EXPRESSION AND FUNCTION OF VPR IN HIV-1-INFECTED T CELLS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 265) J F Wang1, J Shackelford1, C Casella2, N Selliah1, M Karuppiah3, D Weiner3, D Gabuzda4, and T Finkel1,3 Here, we show that Vif modulates the expression, and, therefore, the function, of a critical viral protein, Vpr, in HIV-1 infected T cells. These data suggest that Vif might contribute to the pathogenesis of HIV-1 infection through the regulation of other host cellular or viral proteins in addition to APOBEC3G. |
| 266 | HIV-1 VPR PROMOTES G2/M CELL CYCLE ARREST BY BINDING TO 14-3-3 PROTEINS AND BY FACILITATING COMPLEX FORMATION WITH Cdc25C INDEPENDENTLY OF THE LATTER'S PHOSPHORYLATION STATUS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 266) Tomoshige Kino1, A Gragerov2, A Valentin2, M Tsopanomihalou2, G Ilyina-Gragerova2, R Erwin-Cohen2, G Chrousos1, and G Pavlakis2 These results indicate that Vpr promotes cell cycle arrest at the G2/M phase by facilitating association of 14-3-3 and Cdc25C independently of the latter’s phosphorylation status. |
| 267 | NEF-INDUCED ALTERATION OF THE EARLY/RECYCLING COMPARTMENT CORRELATES WITH ENHANCEMENT OF HIV-1 INFECTIVITY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 267) R Madrid1, K Janvier1, D Hitchin2, J Day2, S Coleman2, C Noviello2, J Bouchet1, A Benmerah1, J Guatelli2, and Serge Benichou1 Since this motif is also required for the Nef-mediated enhancement of the infectivity of virions produced by CD4-negative cells, these results indicate that the functional impairment of the early/recycling compartment induced by Nef may directly relate to optimal viral infectivity. |
| 268 | HIV-1 NEF DISRUPTS MHC-I TRAFFICKING BY RECRUITING AP-1 TO THE MHC-I CYTOPLASMIC TAIL Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 268) Jeremiah Roeth, M Williams, M Kasper, T Filzen, and K Collins In sum, our evidence suggests that binding of AP-1 to the Nef/MHC-I complex is an important step required for inhibition of antigen presentation by HIV. |
| 269 | DOWN-REGULATION OF MAJOR HISTOCOMPATIBILITY-CLASS I MOLECULES IS A SELECTIVE CONSTRAINT TO MAINTAIN HIV-1 NEF Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 269) A Ali, M Dagarag, H Ng, and Otto Yang As a whole, these data indicate that MHC-I downregulation is an important function favoring Nef maintenance due to a net selective advantage in the setting of the general CTL response. Despite strong pressure to disrupt Nef in the setting of Nef-specific CTL, the benefit conferred against other CTL overrides this pressure. |
| Session 57—Poster Abstracts Virus-Cell Interactions: Trans Infection and Inhibition |
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| 270 | INFECTION WITH HIV-1 THROUGH PLACENTAL CELLS REQUIRES TRANSIT FROM RAFTS-ASSOCIATED ORGANELLES TO EARLY ENDOSOMES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 270) Gaël Vidricaire and M Tremblay For the first time, we show that entry of HIV-1 in trophoblasts occurs via a clathrin/caveolin-independent but raft-dependent endocytic pathway. On internalization, HIV-1 particles undertake an unusual transit from lipid-raft rich organelles to early endosomes. Interestingly, this transit appears to be necessary for infection to take place since blocking access to early endosomes resulted in a loss of HIV-1 infection. These data illustrate a completely novel mode of replication for HIV-1 and underscore the complexity of the biology of this retrovirus. This has important implications for mother-to-child transmission of HIV-1. |
| 271 | IMMATURE DENDRITIC CELL-DERIVED EXOSOMES CAN MEDIATE HIV-1 TRANS INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 271) Rebecca Wiley and R Gummuluru Our data suggest that HIV-1 captured by iDCs is transmitted to T cells, without new infection, by exosome-associated exocytosis. Virus particles were found in MVB following endocytosis, and accumulated in iDC sup over time. These particles were infectious and could be enriched by HLA-DR1 (exosome marker) magnetic-bead separation. Since HIV-containing exosome fractions were more infectious than cell-free virus stocks, we hypothesize that the nature of the intracellular compartment that HIV-1 particles migrate to within virus-capturing cells can significantly impact the efficacy of cross-infection of T cells. |
| 272 | PRODUCTIVE AND LATENT INFECTION OF PRIMARY CD4 T CELLS AFTER CELL-TO-CELL TRANSMISSION OF HIV-1 Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 272) J F Wang1, Z Ma1,2, D Levy3, and T Finkel1,2 These data suggest that an actin-dependent cell-to-cell contact transfers HIV-1 viral particles from effector cells to target cells by 2 independent mechanisms. Transfer of viral particles (i.e., p24-positivity) can occur via an endocytic pathway, leading to degradation of the particles in the endosome. In contrast, transfer of productive infection (i.e., GFP positivity) via the virological synapse requires fusion via CD4 and CXCR4. These data have implications for HIV-1 latency and viral spread. |
| 273 | ACTIVATED B LYMPHOCYTES EXPRESS DC-SIGN AND TRANSMIT HIV-1 TO T CELLS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 273) Giovanna Rappocciolo, P Piazza, C Fuller, T Reinhart, P Gupta, D Rowe, M Jais, S Watkins, and C Rinaldo DC-SIGN is expressed on activated B cells, which leads to enhanced infection of T cells in trans. B cells could therefore become vehicles for HIV-1 infection of T cells during antigen processing that involves signaling by activated-CD40L and IL-4-expressing CD4+ T helper cells. This supports a critical role for B cells in the pathogenesis of HIV-1 infection, and suggests new targets for therapeutic strategies. |
| 274 | SEMINAL PLASMA PROMOTES LANGERHANS' CELL ATTRACTION THROUGH SECRETION OF CCL20 BY VAGINAL EPITHELIAL CELLS: INVOLVEMENT IN HETEROSEXUAL HIV TRANSMISSION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 274) W Berlier, M Crémel, P Lawrence, H Hamzeh, A Frésard, F Lucht, C Genin, B Pozzetto, Thomas Bourlet, and O Delézay These data demonstrate that seminal plasma participates to the process of HIV transmission by attracting LCs via the stimulation of CCL20 secretion by epithelial cells. Moreover, they suggest that seminal factors other than IL1β and also present in the sperm of HIV- subjects are involved in this stimulation and could facilitate the transfer of HIV from HIV+ semen to vaginal target cells. |
| 275 | TYROSINE KINASES INVOLVEMENT IN THE SECOND PHASE OF HIV-1 TRANSFER FROM DENDRITIC CELLS TO CD4 T LYMPHOCYTES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 275) Caroline Gilbert, R Cantin, C Barat, and M Trembaly These data suggest that tyrosine kinases of the Src and Syk families play an important role in the regulation of HIV-1 transfer by immature DC and more particularly in the late phase of this process. Additional work is needed to address the exact contribution of each kinase in this phenomenon. |
| 276 | INHIBITION OF CO-RECEPTOR-INDEPENDENT CELL-TO-CELL HIV-1 TRANSMISSION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 276) Berta Bosch1, J Blanco1, M Fernandez-Figueras2, B Clotet1, and J Este1 This novel mechanism of HIV transmission converts CD4 T cells lacking the appropriate co-receptor in HIV carriers that could favor the spreading of HIV, to compartments where antiretroviral drugs could not reach. Further studies of gp120 targeting agents in the co-receptor-independent virus transmission will provide new tools to understand the relevance of this novel mechanism. |
| 277 | CYTOMEGALOVIRUS/ENDOTHELIAL CELL SIGNALLING INDUCES HIV-1 REPLICATION IN RESTING T CELLS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 277) Jason Walker, J Choi, J Pober, and L Alexander Activated endothelial cells induce a microenvironment conducive to HIV-1 replication in circulating memory T cells. This microenvironment allows HIV to broaden the pool of virus-producing T cells by promoting replication in T cells that do not receive fully activating stimulatory signals from antigen-presenting cells (> 95% of T cells in vivo), but rather are suboptimally stimulated by endothelial cells. Additionally, we show that UV-inactivated CMV particles induced MHC II-independent HIV-1-replication enhancement in T cells, suggesting a distinct and physiologically relevant mechanism whereby chronic CMV infection, and activation of endothelial cells via TLR-2 could contribute to HIV-1 replication in dually infected humans. |
| Session 58—Poster Abstracts Virus-Macrophage Interactions |
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| 278 | CCR5 SIGNALING-INDUCED ERK1/2 ACTIVATION BOOSTS R5 HIV-1 REPLICATION IN PRIMARY MONONUCLEAR CELLS G Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 278) Y L Lin1, C Mettling1, B Réant1, J Clot2, and Pierre Corbeau1 Our data show that ERK1/2 are activated via CCR5 and the Gαi pathway during R5 HIV-1 infection and that this activation increases the efficiency of the virus replication. Unveiling the activation pathways contributing to the optimal lentivirus replication in primary cells sheds a new light on HIV-1 pathogenesis and treatment. |
| 279 | GP120 STIMULATION OF TNF-α PRODUCTION BY HUMAN MACROPHAGES IS MEDIATED BY CCR5 THROUGH A PI-3 KINASE AND MAPK KINASE-DEPENDENT PATHWAY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 279) Brian E Tomkowicz, C Lee, and R Collman Thus, our data suggest that TNF-α secretion in human monocyte-derived macrophages following gp120 exposure is mediated by the CCR5 receptor, is dependent on the activation of the MAP kinases p38 and ERK-1/2, and that their activation occurs through a PI3 kinase-dependent pathway. Our findings provide insight into the initial signaling events that occur on HIV-1 binding in macrophages that may contribute to macrophage dysfunction in AIDS, including processes such as AIDS dementia and inappropriate activation where TNF-α secretion plays an important role. |
| 280 | HIV-1 INDUCES CHANGES IN GENETIC NETWORKS INVOLVED IN IMMUNE FUNCTION, SIGNAL TRANSDUCTION, AND A Th2-TYPE SHIFT IN CYTOKINE SECRETION IN HUMAN MACROPHAGES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 280) James Kohler1, J Brown1, C Coberley1, J Sleasman2, and M Goodenow1 The effect of HIV-1 on immune function and signal transduction cascades in MDM is both broad and complex. Macrophages alone, independent of T-helper-cell interaction, can influence a Th2-shift in cytokine patterns in response to HIV-1. Collectively, sentinel changes in gene expression and cytokine expression patterns identify an important role macrophages play as targets for HIV infection and promotion of disease progression. |
| 281 | SELECTIVE REMOVAL OF SUPEROXIDE ANIONS IS CRUCIAL FOR HIV REPLICATION IN HUMAN PRIMARY MACROPHAGES AND PREVENTS PEROXYNITRITE-MEDIATED APOPTOSIS IN NEURONS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 281) Stefano Aquaro1, C Muscoli2, M Pollicita1, A Ranazzi1, T Granato3, M C Bellocchi1, A Modesti1, D Salvemini4, V Mollace2, and C F Perno5,6 Results support the role of superoxide anions production in both HIV-1 replication in M/M and its related induction of neurodegeneration. In conclusion, data suggest that SOD mimetic compounds may counteract both HIV-1 replication and HIV-related neuronal damages in combination with other antiretroviral treatments. |
| 282 | HIV-1 NEF PROTEIN INTERFERES WITH M-CSF RECEPTOR SIGNALLNG THROUGH HCK ACTIVATION AND INHIBITS M-CSF BIOACTIVITIES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 282) Shinya Suzu, H Harada, and S Okada Present studies indicate that HIV-1 Nef interferes with M-CSF receptor signaling through Hck activation and thereby inhibits M-CSF functions in monocytes/macrophages. Our findings provide a clue to understanding how monocytes/macrophages contribute to the development and progression of AIDS and to clarifying the role of the Nef-Hck interaction in the disease process. |
| 283 | ACTIVATION OF TOLL-LIKE RECEPTOR-3-INDUCED ANTI-HIV ACTIVITY IN PRIMARY HUMAN MACROPHAGES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 283) Xinyan Liu1, A Mosoian1, T Chang1, C Vogel1, G Jarvis2, and M Klotman1 Our data indicate that activation of TLR3 in primary human macrophages results in anti-HIV-1 activity similar to activation of TLR4. Down-regulation of HIV-1 co-receptor CCR5, induction of type I IFN, and direct transcriptional inhibition contribute to TLR ligands-mediated HIV-1 inhibition. This study provides evidence that innate immunity induced by TLR3 ligand can inhibit HIV infection in primary human macrophages in vitro. |
| 284 | INDEPENDENT EVOLUTION OF HIV-1 BETWEEN BLOOD MONOCYTES AND CD4+ T CELLS DURING THE COURSE OF THE INFECTION WITH AND WITHOUT ANTIRETROVIRAL THERAPY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 284) Rafael Zioni, Y Hwangbo, H Zhu, J Fulcher, X Lin, L Corey, and T Zhu HIV-1 evolves in the monocytes as separate compartment as the disease progress, and monocytes may be an important source of actively replicating virus during HAART treatment. |
| Session 59—Poster Abstracts Pathogenesis of Primary HIV Infection |
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| 285 | GASTROINTESTINAL CD4+ T CELLS HARBOR A HIGHER VIRAL BURDEN THAN PERIPHERAL BLOOD CD4+ T CELLS IN PRIMARY HIV-1 INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 285) Saurabh Mehandru1, M Poles1,2, D Boden1, A Horowitz1,2, K Tenner-Racz3, A Shet1, A Hurley1, P Racz3, and M Markowitz1 In subjects with acute and early HIV-1 infection, a higher percentage of the GI CD4+ T cells have a memory phenotype and express markers of immune activation compared to PB. GI CD4+ T cells in acute and early HIV-1 infection proliferate more compared to HIV-uninfected subjects at this stage of infection. GI CD4+ T cells have a higher viral burden compared to PB CD4+ T cells. Limited data suggest that GI CD4+ T cells have a higher degree of productive infection than PB CD4+ T cells. The predominance of HIV-1 DNA and RNA in the GI CD4+ T cells in acute and early HIV-1 infection suggests a pivotal role for the gut in pathogenesis of HIV infection. |
| 286 | EARLY PROLIFERATION AND APPARENT LOSS OF CCR5+ CD38+++ ANTIGEN-SPECIFIC CD4+ TH1 EFFECTOR CELLS DURING PRIMARY HIV-1 INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 286) J Zaunders1, D Kaufmann2, M Munier3, S Ip3, P Grey3, D Smith3, T Ramacciotti3, D Quan4, R Finlayson5, J Kaldor3, E Rosenberg2, B Walker2, D Cooper3, A Kelleher3, and Phaedra Study Team These results suggest that the very early antiviral response in HIV-1 infection includes proliferating, highly activated CCR5+CD4+ effector cells, which are susceptible to both apoptosis and cytopathic infection with HIV-1, and rapidly decline. |
| 287 | HIGH FREQUENCY OF APPARENT HIV-1 SUPERINFECTION IN A SEROCONVERTER COHORT Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 287) Robert Grant1,2, J McConnell1, J Marcus1, G Spotts2, T Liegler1, R Brennan2, and F Hecht2 Acquisition of NNRTI-resistant HIV-1 by apparent superinfection may reflect its high prevalence in the community and preserved replication capacity. The high rate of apparent superinfection in seroconverter cohorts contrasts with the lack of superinfection detected in chronically infected cohorts analyzed using the same virological methods. Less common superinfection in chronic infection may reflect development of protective immune responses against partner viruses, antiretroviral use, or virological interference. |
| 288 | HIV-1 GROUP M SUPERINFECTION IN A HIV-1 GROUP O-INFECTED PATIENT Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 288) J C Plantier1, V Lemée2, I Dorval3, M Gueudin2, J Braun2, P Hutin3, Annick Ruffault4, and F Simon5 Superinfection, which could be clearly shown in our patient because the large antigenic and molecular divergence between groups M and O, is likely to be a frequent phenomenon. The total lack of cross-protection between HIV types, groups, and subtypes is striking and underlines the need for close molecular epidemiological monitoring worldwide. |
| Session 60—Poster Abstracts HIV Diversity and Evolution during Primary Infection |
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| 289 | TRANSMISSION OF DRUG RESISTANT HIV-1 IN PATIENTS WITH ACUTE AND EARLY HIV-1 INFECTION IN 2003 TO 2004 Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no.. 289) Anita Shet, H Mohri, L Berry, S Mehandru, A Hurley, V Simon, D Boden, and M Markowitz Transmission of drug resistant HIV, particularly those variants resistant to NNRTI and multiple classes of ARV rose significantly in 2003 to 2004. We did not detect transmitted resistance to enfurvitide in a subset of individuals, including 10 subjects with multi-drug resistant HIV-1. These data support continued effort to monitor for transmitted drug-resistant variants and underscore the need for better prevention efforts amongst the treated infected population. |
| 290 | MARKED DIFFERENCES IN GENETIC DIVERSIFICATION OF HIV-1 POL AND ENV IN EARLY HIV-1 INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no.. 290) Mary Kearney1, S Palmer1, F Maldarelli1, M Polis2, J Mican2, R Stephans3, D Rock4, J Margolick5, J Mellors6, and J Coffin1 Our analysis shows that the variable regions of env diversify rapidly after HIV-1 infection, whereas pol remains remarkably homogeneous. Prior studies have suggested that multiple variants of HIV-1 can be transmitted, based on substantial diversity in the V1/V2 or V3 domains of env in early infection. Our findings indicate that the early sequence diversity in env, including insertions in V1/V2, can result from transmission of a single variant followed by rapid evolution of divergent variants. |
| 291 | GENETIC VIRAL EVOLUTION IN PATIENTS INCLUDED IN CLUSTERS AT PRIMARY INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no.. 291) Sabine Yerly1, H Gunthard2, M Cavassini3, J P Chave4, P Schmid5, H Furrer6, V Schiffer7, and L Perrin1 After years of follow-up, RT and PR sequences from PHI patients infected by the same strains still form clusters with bootstrap values > 98% despite within-individual evolution. Amino acid changes occurred preferentially at defined RT and PR positions. Changes were host dependent and not related to viral strain. |
| Session 61—Poster Abstracts Pathogenesis: Host Genetic Studies |
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| 292 | GNB3 C825T POLYMORPHISM AND RESPONSE TO ANTIRETROVIRAL COMBINATION THERAPY IN HIV-1-INFECTED PATIENTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no.. 292) Norbert H Brockmeyer1, A Kasper1, A Potthoff1, R Schlottmann1, C Nabring1, K H Jöckel2, and W Siffert2 The GNB3 C825T polymorphism appears associated with short-term success of HAART treatment in HIV-1-infected patients. Despite the strongest suppression of viral load, CD4+ cells do not increase in patients with TT genotype. |
| 293 | POPULATION-SPECIFIC ASSOCIATIONS OF CTLA4 GENOTYPES WITH HIV-1 DISEASE PROGRESSION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no.. 293) Wenshuo Shao1, A Lazaryan1, M Dorak1, A Penman-Aguilar1, C Wilson1, J Margolick2, J Goedert3, M Prins4, J Tang1, R Kaslow1, for the MACS, DCG, REACH and ACS cohorts CTLA4 genotypes showed heterogeneous associations with clinical and virological outcomes following HIV-1 infection. The effects appeared to vary with time and among the cohorts. Future studies of variants in the neighboring, biologically related genes CD28 and ICOS on human chromosome 2q33 may help explain the observed heterogeneity. |
| 294 | RARE ALLELE ADVANTAGE: HIV-1-INFECTED ADULTS CARRYING RARE HLA CLASS I B ALLELES HAVE LOWER CD8+ T-CELL ACTIVATION LEVELS INDEPENDENT OF HIV-1 RNA LEVEL Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no.. 294) Jason Barbour, M McGrath, J Oksenberg, and F Hecht Among recently infected adults, carrying at least 1 rare class I B allele was associated with lower T-cell activation independent of HIV-1 RNA levels. Common class I alleles have likely forced progressive epitope escape in the pool of circulating viruses over the course of the epidemic. To exploit what little CD8+ effector function is available, patients carrying 2 common class I B alleles may develop compensatory and ultimately aberrant levels of activation. |
| 295 | GENETIC CORRELATES OF RESISTANCE TO HIV INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 295) Mara Biasin1, G Magri1, D Trabattoni1, F Lissoni1, Y Kanari2, F Fasano1, C Bergamaschi1, L Piacentini1, M Myazawa2, and M Clerici1 These findings, besides clarifying the mechanisms regulating the synthesis of APOBEC, indicate the presence of a distinctive genetic background for the HIV-1 ESN and allow us to formulate the hypothesis that high levels of APOBEC3G and APOBEC3F could be associated with resistance to retroviral infections in humans. |
| 296 | DIFFERENTIAL EFFECTS OF INDIVIDUAL B58 SUPERTYPE ALLELES ON CONTROL OF HIV-1 DISEASE IN NATIVE AFRICANS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 296) Aleksandr Lazaryan1, E Lobashevsky1, J Mulenga2, E Karita3, S Allen4, J Tang1, and R Kaslow1 In Zambians with subtype C and Rwandans with subtype A HIV-1 infection, individual B58s alleles, rather than the supertype as a whole, showed strikingly different associations with the available outcome measures. These findings caution against treating the B58s as a homogeneous designation in the context of HIV/AIDS in every population. |
| Session 62—Poster Abstracts Viral Reservoir Characterization |
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| 297 | MODELING T-CELL RECEPTOR EXCISION CIRCLES AND 5-BROMO-2'-DEOXYURIDINE LABELED NAÏVE T CELLS DURING HIGHLY ACTIVE ANTIRETROVIRAL THERAPY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 297) Michele Di Mascio1, I Sereti1, L Matthews1, V Natarajan2, C Yoder1, E Jones3, C Chow3, J Metcalf1, M Polis1, I Sidorov4, D Dimitrov4, and J Kovacs3 This model suggests that the HIV-induced increase in naïve T-cell proliferation is an ineffective compensatory mechanism in response to a loss of naïve T cells that have been activated into memory cells. Alternatively, the first effect of activation might consist of inducing naïve T cells to proliferate faster without losing their phenotype, bringing these cells closer to the priming activation threshold. The short-term effect of HAART on T-cell turnover is mainly dominated by the normalization of this proliferation, followed by a delayed normalization of the death rate. |
| 298 | PERSISTENCE OF ARCHIVED VIRUSES WITH A UNIQUE TROPISM IN ANTIRETROVIRAL-TREATED INDIVIDUALS WITH DRUG-RESISTANT HIV Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 298) Wei Huang1, T Neilands2, J Whitcomb1, T Wrin1, J Toma1, S Fransen1, J Martin2, C Petropoulos1, and S Deeks2 Patients virologically failing combination antiretroviral therapy may harbor viruses with a tropism that differs from that in plasma. These viruses may impact on response to subsequent R5 inhibitor-based salvage therapy. The relative impact of R5 vs X4 on CD4 T-cell counts will require careful observation in larger cohorts. |
| 299 | IL-7 AS A POTENT INDUCER OF VIRAL STRAIN-SPECIFIC HIV-1 RESERVOIRS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 299) Roger Pomerantz1, F X Wang1, Y Xu1, J Sullivan1, E Sounder1, E Argyris1, E Acheampong1, J Fisher1, M Sierra2, R Najera2, J Kulkosky1, and G Nunnari1 The known immunomodulatory effects of IL-7 could be combined with its ability to stimulate HIV replication from resting CD4+ T-lymphocytes as a unique “one hit” mechanism, in addition to other moieties, to potentially deplete HIV-1 reservoirs and lead to the rational design of novel immune-antiretroviral approaches. |
| 300 | BLOOD MONOCYTES HARBOR VIRUSES UTILIZING MULTIPLE CORECEPTORS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 300) Younong Xu1, H Zhu1, A Van't Wout1, J Lee2, C Dai1, M Jenkins1, T Andrus1, N Llewellyn1, R Zioni1, L Stamatatos1, J Mullins1, M McElrath2, L Corey1,2, and T Zhu1,2 These findings indicate that blood monocytes could harbor viruses with multiple co-receptor usages at acute or late stages of HIV-1 infection, suggesting an important role that monocytes may play as a virus source of the transmission, establishment, and persistence of HIV-1 infection. |
| 301 | IN VIVO EVIDENCE FOR INSTABILITY OF EPISOMAL HIV-1 CDNA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 301) Mark Sharkey1, K Triques1, D Kuritzkes2, and M Stevenson1 Episomal viral cDNAs are labile, and hence are valid indicators of ongoing viral replication in vivo. The replacement of WT episomes by M184V-containing episomes while proviral sequences remained WT indicates that episomal cDNAs are turned over by degradation rather than through death or tissue redistribution of the infected cell itself. |
| 302 | DECAY KINETICS OF PBMC WITH DIFFERENT HIV-RNA EXPRESSION PATTERNS MEASURED AT THE SINGLE-CELL LEVEL USING LIMITING DILUTION COMBINED WITH PATIENT MATCHED REAL-TIME PCR Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 302) Marek Fischer1, P Kaiser1, D Baumann1, R Hafner1, C Schneider1, S Bonhoeffer2, R Weber1, and H Guenthard1 Combination of limiting dilution with patient-matched quantitation of different HIV-RNA allowed to characterize a specific RNA expression pattern of productively HIV-infected cells. Clearance was rapid after initiation of ART, in contrast to the persistence of cells exhibiting attenuated, non-productive RNA expression patterns, most likely representing latently infected cells transcribing HIV-RNA at low levels. Applying this novel method to larger cohorts of HIV-infected patients may allow us to refine our understanding of the population dynamics of HIV-1-infected cells in vivo. |
| 303 | A NOVEL CULTURE SYSTEM THAT ALLOWS HIV-INFECTED ACTIVATED PRIMARY CD4+ T-LYMPHOCYTES TO BECOME LATENTLY-INFECTED QUIESCENT CELLS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 303) Gautam Sahu, J Ji, and M Cloyd These results demonstrate a novel culture system in which activated, proliferating primary CD4+ T cells can be rescued from activation-induced cell death and maintained viably for many months in a non-cycling state. Using this system, we demonstrate the formation of latently infected CD4 T cells in vitro. This system provides the opportunity to study the mechanism of latent HIV infection in primary CD4 T cells in vitro at the molecular level, as well as the biology of chronically HIV-producing primary CD4 T cells that are frequently observed in vivo. |
| 304 | DEFINING FUNCTIONALLY SIGNIFICANT RESERVOIRS FOR HIV-1 IN PATIENTS ON HAART Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 304) Tara Kieffer, R Nettles, H Zhang, Y Han, Y Liu, J Bailey, C Haggerty, M Wind-Rotolo, D Persaud, T Quinn, J Siliciano, and S Ray Two important and disturbing conclusions can be drawn. First, a second major reservoir contributes to persistent viremia in some patients on HAART. Second, the latent reservoir in resting CD4+ T cells is not maintained by ongoing viral replication as its composition does not reflect that of the low-level plasma virus in some patients. Thus the reservoir is intrinsically stable, consistent with the biology of memory CD4+ T cells, and is unlikely to decay even if low-level viremia is further reduced by intensification of HAART. |
| Session 63—Poster Abstracts Pathogenesis: Co-Infection and Other Viruses |
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| 305 | INFLUENCE OF HTLV-2 CO-INFECTION IN VIROLOGICAL AND IMMUNOLOGICAL PARAMETERS OF HIV-INFECTED PATIENTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 305) Sylvina Bassani, J Benito, M Vázquez, C Toro, V Jiménez, and V Soriano HTLV-2 co-infection may exert a protective role on HIV disease progression by lowering HIV replication and immune activation. A predominance of MIP-1β-producing HIV-specific cells in co-infected patients could contribute to reduced HIV replication. |
| 306 | HTLV-1/2 VIRAL LOAD AND AND IMMUNOLOGIC PARAMETERS AMONG HIV-1 CO-INFECTED INDIVIDUALS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 306) Mark Beilke1, M Sirois2, V Traina-Dorge3, J Walls1, R Lorino3, J West1, S Eloby-Childress1, and P Kissinger2 An HTLV-1/2 viral load of > 20,000 copies/106 PBMC, a positive HTLV-1 Western blot, and a positive HTLV-1/2 p19 viral antigen determination, all correlated with higher CD4 and CD8 cell numbers, independent of HIV viral load, recent use of street drugs, or antiretroviral drug use. |
| 307 | ROLE OF SHP-1 DEREGULATION IN HTLV-1 LEUKEMOGENESIS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 307) Jihua Cheng, A Kydd, and W Marasco These studies should provide new insights into biochemical mechanisms of HTLV-1 leukemogenesis and aid in the development of new treatments for this fatal disease. |
| 308 | SIMIAN FOAMY VIRUS INFECTION AMONG HIV-1+ SEX WORKERS AND BLOOD DONORS IN CENTRAL AFRICA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 308) W Switzer, M Kalish, C Yang, A Garcia, A Wright, T Folks, and W Heneine Our study documents SFV infection among different Central African populations. The finding of SFV in samples collected recently and in 1985 from blood donors and sex workers suggests long-standing infection and opportunities for blood-borne and sexual transmission. The observed co-infection with SFV and HIV heightens the importance of defining the clinical and public health consequences of these infections. |
| 309 | FOAMY VIRUS IS NOT CHARACTERIZED BY EXTREME LATENCY IN ITS NATURAL HOST Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 309) Shannon Murray1, M Axthelm2, L Picker2, and M Linial1 Taken together, we suggest that that FV replication is more consistent and widespread than previously thought, and that the host immune system may play a role in controlling FV replication in the small intestine. |
| Session 64—Poster Abstracts Virus-Host Interactions: Antiviral Responses and Mucosal Infection |
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| 310 | NEGATIVE HIV ANTIBODY TEST AND NEGATIVE VIRAL RNA IN A PATIENT WITH DOCUMENTED HIV INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 310) Itzchak Levy1, G Rahav1, M Bakhanashwili1, E Nadir1, and Z Grossman2 We report here for the first time a case in which a patient, who had been unequivocally infected with HIV and then treated with HAART, showed no evidence of infection after treatment was discontinued and remained apparently infection-free at the time of reporting 4 years later. |
| 311 | α-DEFENSIN-1 HAS A DUAL ROLE IN ANTI-HIV-1 INNATE IMMUNITY: EFFECTS ON THE VIRION AND THE CELL Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 311) T Chang, J Vargas, Jr, A DelPortillo, and Mary Klotman Our studies demonstrate that in the absence of serum, α-defensin-1 may act directly on the virus but in the presence of serum, its effects are on the cell where it inhibits HIV-1 replication at the steps of nuclear import and transcription. At least one of the cellular effects associated with HIV inhibition is interference with PKC signaling in CD4 T cells. Studying the complex function of α-defensin-1 in innate immunity against HIV has implications for prevention as well as therapeutics. |
| 312 | GB VIRUS C ENVELOPE GLYCOPROTEIN E2 ELICITS ANTIBODIES THAT IMMUNOPRECIPITATE HIV PARTICLES AND NEUTRALIZE HIV INFECTIVITY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 312) Jinhua Xiang1, J McLinden1, Q Chang1, D Klinzman1, T Kaufman1, A Engel2, G Hess3, D Zdunek2, and J Stapleton1 GBV-C E2 protein contains a conformational antigenic region that induces antibodies that are neutralizing against HIV. This may explain the survival advantage of prior GBV-C infection in HIV-positive people observed in several clinical studies. Furthermore, it provides a novel, potentially disease-modifying HIV vaccine immunogen and may direct the design of novel anti-HIV therapies. |
| 313 | HUMAN α-DEFENSIN-1 AND RHESUS θ-DEFENSIN-1 INHIBIT HIV-1 REPLICATION BY DIFFERENT MECHANISMS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 313) Aprille Matthews, L White, P Tran, M Selsted, and D Camerini Both HNP-1 and RTD-1 down-modulate cell surface CXCR4 expression, however, this requires higher defensin concentrations than are needed to inhibit HIV-1 infection. HNP-1 can inhibit viral replication when added both before and after infection of target cells, whereas, HBD-2 and RTD-1 inhibit infection when added to cells before or at the time of infection. HNP-1 and RTD-1 inactivate X4 HIV-1 directly when incubated with virus prior to infection; however, only HNP-1 effectively inactivates R5 HIV-1. Our results indicate that HNP-1 and RTD-1 inhibit HIV-1 infection by different mechanisms. |
| 314 | MUCOSAL CD4+ T-CELL RESTORATION AND ANTIGEN-SPECIFIC T-CELL RESPONSES IN HIV-1-INFECTED INDIVIDUALS INITIATING THERAPY DURING PRIMARY VS CHRONIC INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 314) Moraima Guadalupe1, E Reay1, S Sankaran1, T Prindiville1, J Flamm2, B Shacklett1, and S Dandekar1 Early initiation of ART was more effective at restoring or maintaining mucosal CD4+ T-cell numbers than initiation during chronic infection. However, a delay in restoration of mucosal CD4+ T cells was observed in both groups. Although weak HIV-specific CD8+ T-cell responses were observed in peripheral blood mononuclear cells of patients on ART, strong HIV-specific CD4+ T-cell responses were detected in jejunal LPL of individuals following 1 to 5 years of ART. This finding suggests that long-term ART can restore HIV-specific CD4+ T-cell function in the gastrointestinal mucosa. |
| 315 | CD4+CD25+hi T REGULATORY-CELL DYNAMICS DURING ACUTE AND CHRONIC HIV INFECTION, AND RESPONSE TO THERAPY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 315) Anita Shet1, S Mehandru1, P Lopez1, A Horowitz1, A Hurley1, D Unutmaz2, D Boden1, and M Markowitz1 CD4+CD25+hi T regulatory cells are expanded during acute HIV infection and decrease over time in untreated chronic HIV infection, presenting a possible target for infection with HIV. TR numbers increase during HAART; however the slower recovery of TR may contribute to persisting defects in immune responses even when CD4+ T cell numbers are restored. Further studies are underway to evaluate TR infectivity and TR-cell function during HAART. |
| 316 | PARALLEL HIV-1-SPECIFIC CD8+ T-LYMPHOCYTE RESPONSES IN BLOOD AND MUCOSA DURING CHRONIC INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 316) F Javier Ibarrondo1, P Anton1, M Fuerst1, H Ng1, J Wong2, J Matud1, J Elliott1, R Shih1, M Hausner1, C Price1, L Hultin1, B Jamieson1, and O Yang1 This study provides a comprehensive analysis of the HIV-1 specific CTL responses in GALT, indicating that they are mirrored in peripheral blood during chronic infection. The pivotal role of this compartment as a portal of entry in acute infection and reservoir for replication in chronic infection underscores the importance of understanding the relationships between blood and gut mucosa immune responses. Elucidating such mechanisms may be important to optimizing vaccine efficacy by eliciting HIV-1-specific immunity in the GALT. |
| 317 | CELLULAR RESISTANCE TO HIV-1 INFECTION MAY EXPLAIN CONTINUED SERONEGATIVITY IN SELECT HIGHLY EXPOSED INDIVIDUALS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 317) Emily Speelmon1,2, D Livingston-Rosanoff2, D Wick2, J Lee2, and M McElrath1,2 The pronounced reduction in CD4+ T-cell susceptibility and corresponding decrease in R0 observed in 4 exposed seronegative subjects and 2 low-risk controls may provide protection from overt HIV-1 infection in vivo in this subset of individuals. Because in vitro infectivity culture conditions do not directly simulate in vivo infection, the reported values of R0 cannot be regarded as true reproductive numbers in vivo. However, the relative values of R0 and TCID50 may reflect significant biological differences between the 2 groups (normal and low HIV-1 susceptibility). Given the low rate of sexual transmission of HIV-1, the markedly diminished R0 values, and increased viral inoculum required to establish infection that we report here may contribute to these volunteers’ continued seronegativity. |
| 318 | SYNTHETIC θ-DEFENSINS, WHICH INHIBIT HIV-1 ENTRY, EXHIBIT DIFFERENT ACTIVITY AGAINST PRIMARY HIV-2 AND SIV ISOLATES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 318) Silvina Masciotra1, S Kennedy1, D Rudolph1, W Wang2, A Cole3, A Waring2, R Lal1, R Lehrer2, and M Owen1 Results from these inhibition assays support previous findings that suggest differences between HIV-1 and HIV-2 entry. The reported decrease in binding and inhibition may be due to the different glycosylation patterns observed between HIV-1 and HIV-2/SIV isolates. Furthermore, these results suggest θ-defensins are not likely to be good therapeutics for HIV-2 infections. |
| 319 | EARLY ANTIRETROVIRAL THERAPY IN SIMIAN IMMUNODEFICIENCY VIRUS INFECTION LEADS TO MUCOSAL CD4+ T-CELL RESTORATION AND ENHANCED GENE EXPRESSION REGULATING MUCOSAL REPAIR AND REGENERATION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 319) Michael George, E Reay, S Sankaran, and S Dandekar Initiation of PMPA therapy in primary SIV infection was effective at restoring mucosal CD4+ T-cell numbers during chronic infection and led to reduced inflammation and promotion of epithelial repair in the intestinal mucosa. Gene expression studies suggest that intestinal epithelial growth and repair pathways could provide potential molecular targets for novel therapeutic approaches to restore intestinal mucosal function during SIV and HIV infections and thereby improve clinical outcome. |
| 320 | CCR5 EXPRESSION IN BLOOD AND CERVICAL TISSUE OF HEALTHY WOMEN Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 320) Kavita Marfatia1, F Priddy2, G Silvestri1, and M Feinberg1 Our data suggest that T lymphocyte HIV co-receptor expression differs in the peripheral and genital compartments of healthy women. Expression of both CCR5 and CXCR4 was high in the cervix, with at least 40% of CD4+ and CD8+ lymphocytes expressing these coreceptors. CCR5 inhibitors as topical or systemic microbicides may be a powerful method to prevent sexual HIV transmission in women. However the functional role of CCR5 and CXCR4 coreceptors in the genital tract should be examined, and studies of CCR5 inhibitors in healthy women should include evaluation of immunologic effects of CCR5 inhibition in the genital tract. |
| 321 | VISUALIZING INDIVIDUAL, FLUORESCENTLY TAGGED HIV-1 PENETRATION IN A CERVICAL EXPLANT MODEL Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 321) Tracy Schmidt, E Forde, and T Hope We have established a novel methodology to visualize individual HIV-1 particles within cervical tissue using photo-activatable GFP virions. This model now allows us to begin to address the question of how HIV-1 is transmitted through the genital mucosa. |
| Session 65—Poster Abstracts (and Session 38—Poster Discussion) Emerging Issues in Monkey Pathogenesis Models |
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| 322 | AIDS-DEFINING CD4+T-CELL LEVELS IN THE ABSENCE OF CLINICAL SYMPTOMS INDUCED BY SIVSMM INOCULATION OF SOOTY MANGABEYS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 322) J Milush1, D Zhou1, A Muthukumar1, E Chacko1, K Cole2, A Barry3, L Demma3, S Staprans3, G Silvestri3, and Donald Sodora1 These data suggest that the CD4-low phenotype is the result of direct viral cytopathicity of the SIVsmm replicating in these 2 SM, as we did not identify any correlation between CD4 decline and immune activation. These CD4-low SM therefore represent a unique model to investigate the direct cytopathicity of SIV in the absence of aberrant immune activation as well as other immune components responsible for preventing progression to clinical AIDS in SM. |
| 323 | GENES THAT MAY BE INVOLVED IN THE PROTECTION OF SIV-INFECTED SOOTY MANGABEYS FROM SIV PATHOGENESIS REVEALED BY MICROARRAY ANALYSIS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 323) Sara Klucking1, D Powell2, H Wu3, M Paiardini1, B Cervasi1, M Halloran3, G Silvestri1, S Staprans1, and M Feinberg1 Transcriptional profiles of SIV-infected SM and HIV-infected human lymphocytes have allowed the identification of genes that may provide clues to the key determinants of disease outcome following viral infection. |
| 324 | CORRELATION OF CD4+T-CELL DEPLETION WITH INCREASED LEVELS OF T-CELL ACTIVATION IN NATURALLY SIV-INFECTED SOOTY MANGABEYS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 324) B Sumpter1, S Gordon1, R Dunham1, P Pagliardini1, C Ibegbu1, J Engram1, H McClure1, A Muthukumar2, D Sodora2, M Feinberg1, S Staprans1, and Guido Silvestri1 We observed an association between decreased CD4+ T-cell counts and increased T-cell activation, indicating that in naturally SIV-infected SM the overall level of immune activation is an important determinant of CD4+ T-cell count. In addition, the occurrence of severe CD4+ T-cell depletion is a rare event during natural SIV infection of SM and, when present, is not associated with any AIDS-related symptoms. |
| 325 | NEW MODEL FOR THE STUDY OF SIV PATHOGENESIS IN NATURAL HOST SPECIES: INFECTION OF CARRIBEAN AFRICAN GREEN MONKEYS WITH SIVagm.sab Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 325) I Pandrea1, C Apetrei1, J Dufour1, N Dillon1, B Poonia1, O Diop2, M Muller-Trutwin3, R Bohm1, P Marx1, A Lackner1, and Ronald Veazey1 Due to similarities of virological and immunological parameters of the SIVagm infection in African and Caribbean African green monkeys, the latter seem to be a useful alternative to African monkeys. Caribbean African green monkeys are available in large numbers and at relatively low cost; therefore they represent a valuable tool for the study of SIV infection in their natural host. Moreover, this study demonstrates that, as in macaques, CD4 T-cell depletion occurs preferentially in the gastrointestinal tract. This calls for further investigation of the mechanisms controlling the deleterious effects of SIV in their natural hosts. |
| 326 | AIDS IN AFRICAN NONHUMAN PRIMATE SPECIES: PATHOLOGICAL FINDINGS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 326) I Pandrea, X Alvarez, B Gormus, C Apetrei, V Traina-Dorge, P Marx, G Baskin, A Lackner, and Ronald Veazey Our study showed that neoplasia, severe weight lost, lymphocytic interstitial pneumonia, lymphoid depletion, opportunistic infections, and giant cell disease are present in immunodeficient African NHP. Despite the rarity of immunodeficiency cases in African NHP (which may explain why AIDS went undetected until now), when cases are pulled together the spectrum and the morphology of the lesions are identical to those encountered in macaques with AIDS. |
| 327 | SIV ADAPTATION TO A NEW HOST INVOLVES THE PREFERENTIAL AMPLIFICATION OF A DISCRETE SUBSET OF ENVELOPE GENOTYPES FROM WITHIN THE DIVERSE VIRAL QUASI-SPECIES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 327) L Demma1, J Logsdon2, Thomas Vanderford3, M Feinberg4, and S Staprans5 Selection pressures in natural sooty mangabey hosts have led to remarkable V1V2 plasticity. Upon transmission to a new host species (rhesus macaques), the replicative advantage of a subset of env variants likely relates to features of target cells or receptors that are specific to the new host environment. Understanding the biologic basis for this convergent selection of env sequences, which may involve CD4-independent engagement of the CCR5 co-receptor, could help to elucidate determinants of successful SIVsm cross-species transmission. |
| 328 | PASSAGE OF SIV IN CHINESE RHESUS MACAQUES MAY INCREASE VIRAL VIRULENCE AND DEVELOP AIDS MORE RAPIDLY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 328) Binhua Ling, R Veazey, L Martin, and P Marx Passage of SIVmac increased the virus virulence. Infected Ch rh developed AIDS more quickly. Immunophenotyping of Ch Rh MHC is needed for the simian immunodeficiency virusmac pathogenesis in this macaque subspecies. |
| Session 66—Poster Abstracts Pathogenesis: Determinants and Cellular Factors |
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| 329 | C-C CHEMOKINE CCL2 IS DIFFERENTIALLY REGULATED IN HIV-1-INFECTED INDIVIDUALS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 329) Abdul Ansari, H Heiken, and R Schmidt The comparative gene expression profiling reveals an upregulation in the transcript of several inflammatory chemokine/cytokine genes in HIV-1 viremic individuals. Genes upregulated in the viremic state, in particular CCL2 gene may therefore serve as an indicator and possibly an enhancer of HIV-1 replication, represented by high viral load in HIV-1 viremic patients. Inhibition of increased CCL2 production could provide a new therapeutic intervention in HIV-1 infection. |
| 330 | HIGHER REPLICATIVE CAPACITY OF HIV-1 CIRCULATING RECOMBINANT FORM OVER ITS PARENTAL SUBTYPES: IMPLICATIONS FOR PREDOMINANCE OF CRF02_AG IN WEST AND WEST CENTRAL AFRICA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 330) Harr F Njai1, K Arien1, C Clybergh1, Y Gali1, L Kestens1, E Arts2, M Peeters3,4, and G Vanham1 High ex vivo fitness of CRF02_AG could explain its dominance in the HIV epidemic. |
| 331 | CONSTRAINED HIV REPLICATION BY INHIBITING CELL PROLIFERATION YET MAINTAINING CELL ACTIVATION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 331) Andrea Foli, A Groff, L Lova, L Boveri, E Sugliano, J Lisziewicz, and F Lori Inhibition of cell proliferation, in the presence of maintained cell activation, is sufficient to limit viral replication in cells latently infected with HIV. One implication is that modulation of cell proliferation without suppression of cell activation may inhibit HIV without major interference with the ability of T cells to mount a proper immune response. |
| 332 | WHOLE BLOOD INTERLEUKIN-18 CONCENTRATION DURING INITIAL HIV INFECTION IS ASSOCIATED WITH HIV SUPPRESSION AND REDUCED CXCR4 HIV CO-RECEPTOR EXPRESSION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 332) L Shapiro1, Carrie Sailer1, C Dinarello1, S MaWhinney1, J Forster1, A Landay2, L Al-Harthi2, R Schooley1, and C Benson1 This is the first prospective study assessing whole blood IL-18 in persons infected with HIV. After controlling for ART use and week and duration of ART, increased circulating IL-18 predicted a reduced plasma HIV RNA level, a finding consistent with an antiretroviral IL-18 effect. Increased IL-18 also predicted reduced CXCR4 co-receptor expression on CD4+ T cells, suggesting that IL-18 may block HIV entry into cells by constraining receptor availability. Further studies of the role of IL-18 in the pathogenesis of HIV disease and of possible therapeutic use of IL-18 are warranted. |
| 333 | PRELIMINARY EVIDENCE OF DIFFERENCES IN PLASMA GHRELIN LEVELS IN AFRICAN AMERICAN PATIENTS WITH HIV-RELATED WASTING COMPARED TO SERONEGATIVE CONTROLS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 333) Keith Crawford1, J McNeil1, K Kumar2, and J Kwagyan1 Our observations, while preliminary, provide the first evidence for an association between ghrelin levels and HIV-related wasting. Because of the role of ghrelin in r-hGH secretion, deficiencies in ghrelin may underlie r-hGH deficiency in advanced HIV disease. Ghrelin may be a novel target for treatment of wasting and immune deficiency in HIV disease. |
| 334 | MUCOSAL GENE EXPRESSION PROFILES AND CD4+T-CELL PERCENTAGES ARE CHARACTERISTIC OF THE CLINICAL OUTCOME IN LONG-TERM HIV-INFECTED NON-PROGRESSORS AND CHRONICALLY HIV-INFECTED PATIENTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 334) Sumathi Sankaran1,3, M Guadalupe1,3, E Reay1,3, J Flamm2, T Prindiville3, and S Dandekar1,3 Genes regulating inflammation and cellular activation distinguished the patients with diverse clinical outcomes. Regulators of T-cell function dominated the expression profile in LTNP, while inflammation and tissue injury dominated that of HVL. |
| 335 | SYNCYTIUM-INDUCING VIRUS ASSOCIATED WITH HIV-MEDIATED INTESTINAL MALABSORPTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 335) Kevin Michael Rufner1, L Lai2, C Thorpe1,3, C Wanke1,3, and T Knox1,3 Subjects infected with SI display increased clinical and laboratory evidence of malabsorption. A majority of HIV-infected subjects have easily detectable pro-inflammatory cytokines in their duodenal fluid. Further studies elucidating the intestinal microenvironment in HIV-induced malabsorption are needed. |
| 336 | CD38CD8 EXPRESSION PROSPECTIVELY PREDICTS CD4 DECLINE INDEPENDENT OF PLASMA HIV-1 VIRAL LOAD, USE OF HAART OF HIV-1 RESISTANCE PROFILE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 336) Jeffrey Klausner1, M Bilezikjian1, M Krone2, M Gesner3, S Forte1, R Donovan3, and H Sheppard3 CD8CD38 expression in patients predicted declines in CD4 T-cell counts independent of plasma HIV-1 viral load, use of HAART or HIV-1 resistance profile validating the dominant role of immune activation in HIV pathogenesis. While further studies are needed to demonstrate the clinical benefit of monitoring CD38CD8 expression, clinical trials should include CD38CD8 monitoring and therapeutic discovery for HIV disease should additionally focus on modifying immune activation. |
| 337 | DDIT4: DNA-DAMAGE-INDUCIBLE TRANSCRIPT 4 INHIBITS APOPTOSIS IN HIV-1-INFECTED T CELLS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 337) Jiyi Yin1, D Shivers1, and T Finkel1,2 Our data suggest that DDIT4 protects HIV-1 infected human CD4 T cells from apoptosis and increases HIV-1 infection. DDIT4 may represent a novel molecular target for drug design. |
| 338 | REGULATION OF IL-7 RECEPTOR (CD127) ON CD8+ T CELLS BY IN VITRO HIV INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 338) Agatha Komsic-Vranjkovic, E Faller, P MacPherson, and J Angel As seen in vivo, HIV infection of PBMC in vitro results in the down-regulation of CD127 surface expression on CD8 cells. This effect appears to be due to the activity of soluble factor(s) present in HIV-infected PBMC cultures. Candidate proteins include TNF-α and IL-7, the roles of which are being evaluated with neutralizing antibody experiments. Further elucidating the mechanism(s) of CD127 down-regulation will provide important insights into the immunopathogenesis of HIV disease. |
| 339 | THE SELECTION OF HIV-1 DURING SEXUAL TRANSMISSION: DIFFERENCES IN GP160 DIVERSITY IN MALE-TO-FEMALE VS FEMALE-TO-MALE TRANSMISSION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 339) Oliver Laeyendecker1, J Gamiel2, J Shepard2, X Li2, D Serwadda3, N Sewankambo3, F Wabwire-Mangen3, F McCutchan4, J Toma5, W Huang5, R Gray2, M Wawer6, and T Quinn1,2 These results demonstrate a potential difference in the selection of viral variants that occurs during male-to-female vs female-to-male transmission of HIV. |
| Session 67—Poster Abstracts Pathogenesis: Determinants and Viral Factors |
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| 340 | MECHANISM FOR THE EMERGENCE OF LESS PATHOGENIC HIV-1 STRAINS DURING HAART Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 340) Nitin Saksena1, Y Wang1, W Dyer2, J Sullivan2, and C Workman3 Certain antiretroviral drug combinations may affect the cell surface expression of CXCR4. These studies, which were statistically significant, may have implications also in HIV neuropathogenesis in the era of HAART, as CCR5 using strains are macrophage tropic and are critical in HIV infection of the brain. |
| 341 | UNIQUE CONTRIBUTION OF V5-gp41 TO HIV-1 ENVELOPE-MEDIATED CYTOPATHICITY IN THE THYMUS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 341) Eric Meissner, N Coffield, and L Su The V5-gp41 region of the R3A Env is partially responsible for the unique thymic pathogenesis of the R3A Env. Furthermore, in spite of the clear contribution of V1/V2 to R3A entry in vitro, this property has no relevance for pathogenesis in the context of the thymic microenvironment. These data highlight the disconnection between in vitro and in vivo cytopathicity and point to a unique contribution of V5-gp41 to thymic pathogenesis through an as-yet unresolved mechanism. |
| 342 | HIV- ENVELOPE DIVERSITY CORRELATES WITH IN VITRO REPLICATION CAPACITY AND PREDICTS SPONTANEOUS CONTROL OF PLASMA VIREMIA AFTER TREATMENT INTERRUPTIONS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 342) B Joos1, A Trkola1, M Fischer1, H Kuster1, C Leemann1, J Böni2, A Oxenius3, D Price4, R Phillips5, J Wong6, B Hirschel7, R Weber1, Huldrych Günthard1, and the Swiss HIV Cohort Study In summary, lower pretreatment viral diversity was associated with spontaneous control of viremia, reduced viral fitness, and higher neutralizing antibody titers, suggesting a link between viral diversity, viral fitness, and neutralizing antibody activity. |
| 343 | VIRAL KINETICS IN ACUTE SIV/SHIV INFECTION: ESTIMATION OF THE BASIC REPRODUCTIVE RATIO Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 343) Hiroshi Mohri1, R Ribeiro2, N Mushtaq1, R Bohm3, A Gettie1, A Perelson2, and D Ho1 The R0 values of SHIV162P3 (IV) and SIVmac251 (IVAG) in acute infection in plasma and LN were estimated, which provide a quantitative target for vaccine efficiency. This study also highlights local differences among LNs in infected cell growth rates. |
| 344 | IMPAIRED HIV-1 REPLICATIVE FITNESS IN ATYPICAL VIREMIC LONG-TERM NON-PROGRESSOR INDIVIDUALS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 344) Jan Weber1, R Assad2, J Weberova1, M Lederman2, and M Quinones-Mateu1 Intrinsic viral characteristics have been associated with delayed progression to AIDS, particularly in LTNP individuals. We analyzed a subset of LTNP patients with atypical high viremia and demonstrated that similar to the phenomenon observed in patients with a “discordant response” to antiretroviral therapy (i.e., high CD4+ cell counts with detectable viral load), reduced viral replicative fitness seems to correlate with late disease progression in untreated individuals. |
| 345 | HIV-1 REPLICATION CAPACITY AS AN INDEPENDENT PREDICTOR OF PRE-TREATMENT CD4 LYMPHOCYTE COUNT Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 345) Charles Hicks1, J Eron2, P Keiser3, J Stout1, S Napravnik2, J Giner1, P Menezes2, C Castellano1, J Weidler4, T Korich4, and M Bates4 These data suggest that more advanced HIV is associated with both the quantity of viral replication and the fitness of the virus, as measured by the RC assay. RC appears to measure an intrinsic viral characteristic influencing HIV-1 disease progression independently of the magnitude of viral load. |
| 346 | X4 HIV-1 INDUCES APOPTOSIS IN IMMATURE THYMOCYTES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 346) S Choudhary1, D Powell2, R Walker2, C Walsh1, J Anderson3, V Planelles3, and D Camerini1 X4 HIV-1 infection induces apoptosis primarily in DP thymocytes, contributing to thymocyte depletion by killing cells both directly and indirectly. HIV-1 induces apoptosis in thymocytes through both intrinsic and extrinsic pathways and involves caspases. |
| 347 | EVOLUTION OF PATHOGENIC HIV-1 VARIANTS WITHIN GUT-ASSOCIATED LYMPHOID TISSUE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 347) Marcel Curlin1, D Mai1, J Elliott2, P Anton2, and J Mullins1 In this analysis of HIV-1 pol sequences, resistance to NRTI drugs appears to be more heavily represented in GALT than in blood. Appearance of the X4 co-receptor usage phenotype in GALT and PBMC may precede its appearance in plasma. X4-tropic viruses appear to evolve from rapidly replicating viral subpopulations under diversifying selective pressure. Further studies will be required to evaluate these observations. |
| 348 | CYSTEINE MUTATION IN HIV-1 NEF ASSOCIATED WITH SLOWED AIDS DISEASE PROGRESSION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 348) Martin Tolstrup, A Laursen, M Duch, F Skou Pedersen, and L Ostergaard The functional nature of the Nef protein that is impeded by this mutation and its relationship to long term nonprogression remains unclear. |
| 349 | LACK OF TEMPORAL STRUCTURE FOR THE SHORT-TERM VIRAL EVOLUTION IN HIV-1 ASYMPTOMATIC NAÏVE PATIENTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 349) Gonzalo Bello1, C Casado2, S García3, C Rodríguez3, J del Romero3, and C López-Galíndez2 This study demonstrates the existence of at least 2 different patterns of short-term HIV-1 evolution: 1 pattern, characterized by the existence of a temporal structure similar to that previously described, and driven by non-synonymous mutations; the other, not yet described in untreated patients, characterized by a lack of temporal structure with random fluctuations of the evolutionary parameters caused by synonymous mutations. |
| 350 | FEW MUTATIONS IN THE 5´ LEADER REGION MEDIATE FITNESS RECOVERY OF DEBILITATED HUMAN INMUNODEFICIENCY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 350) Antonio V Borderia1, E Yuste2, E Domingo3, and C López-Galíndez1 Large population passages have promoted the recovery in fitness of 4 debilitated viral populations. Unusual distribution of mutations in the 5’-untranslated leader region indicates the importance of the binding of the tRNA to the primer-binding-site loop and the initiation of reverse transcription. In addition, reversions appeared in high proportion, this fact together with the prevalence of non-synonymous replacements could disclose the operation, during large population passages, of a strong positive selection for optimal HIV-1 replication. |
| 351 | R5 AND X4 TROPIC HIV-1 ENVELOPE-MEDIATED MEMBRANE FUSION IS ASSOCIATED WITH DISEASE STAGE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 351) Wei Huang1, S Fransen1, J Toma1, T Wrin1, S Little2, D Richman2, S Deeks3, J Whitcomb1, and C Petropoulos1 Patient viruses exhibit broad differences in env-mediated membrane fusion. The envelope gp120 surface protein is a strong determinant of membrane fusion activity. Highly fusogenic viruses, including PBMC-derived viruses, were associated with increased susceptibility to CD4 inhibition. A comparison of plasma derived viruses indicated that both X4- and R5-tropic viruses from chronic infection are more fusogenic than R5-tropic viruses from recent infection. |
| 352 | SELECTION AND EVOLUTION OF V1-V2 LENGTH AND GLYCOSYLATION OF TRANSMITTED HIV-1 VARIANTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 352) Manish Sagar1, B Chohan1, D Lang2, X Wu1, B Korber2, L Lavreys3, B Richardson1, and J Overbaugh1 Heterosexually transmitted subtype-A viruses have shorter and less glycosylated envelope variable loops early in infection, but acquire glycosylation sites over the course of infection. Because of possible differences in the mode of transmission, there is no apparent selection for shorter and less glycosylated envelope variable loops in subtype-B transmissions. |
| 353 | A PATHOGENIC SIMIAN-HUMAN IMMUNODEFICIENCY VIRUS THAT USES CCR5 AS CO-RECEPTOR AND ENCODES HIV CLADE C ENV Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 353) Ruijiang Song1,4, S Mirshahidi1,4, A L Chenine1,4, C McCann1,4, T Wang1,4, P L Li1,4, K Buckley1, R Grisson1,4, J Whitney1,4, R Rasmussen1,4, H Ong1, C Wood2, H McClure3, and R Ruprecht1,4 These results indicate that SHIV-1157ipd is a pathogenic R5 clade C SHIV. Because co-receptor usage and the gradual pathogenicity of SHIV-1157ipd reflect the tropism of the most frequently transmitted form of HIV and the disease progression pattern in humans, SHIV-1157ipd and/or SHIV-1157ipd3 may represent ideal strains to evaluate AIDS vaccines. |
| Session 68—Poster Abstracts Molecular Epidemiology: Recombination and Recombinants |
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| 354 | RECOMBINATION MAKES AN IMPORTANT CONTRIBUTION TO HIV-1 GENETIC DIVERSITY IN VIVO Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 354) C Charpentier1, T Nora1, O Tenaillon2, F Clavel1, and Allan Hance1 The evaluation of plasma-derived infectious clonal viruses provides strong evidence that prior recombination contributes to the diversity among contemporary viruses from a given patient. High recombination rates were observed throughout the genome, allowing the association of distinct genetic determinants in novel combinations. |
| 355 | HIGH-FREQUENCY OF RECOMBINANT A AND D HIV-1 SUBTYPES IN A POPULATION FROM UGANDA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 355) Okumu K'Aluoch1, R Donovan1, B Barugahare2, P Mugyenyi2, H Sheppard1, and H Cao1 Sequencing of at least 2 regions of HIV-1 genome show that at least 20% of patients in this cohort have recombinant subtypes. The genetic recombination reflects the predominant subtypes, A and D, circulating in Uganda. This rate of recombination may be an indication that superinfection and/or co-infection are more common considering that 2 different virus subtypes must infect the same individual for recombination to occur. The implications of this rate of recombination for viral factors such as fitness, pathogenicity, transmissibility, and the host response need to be elucidated; these factors could have an important impact on vaccine development. |
| 356 | CHARACTERIZATION OF HIV-1 UNIQUE RECOMBINANT FORMS EMERGING IN WESTERN YUNNAN PROVINCE: IMPLICATION FOR THE GENESIS OF EXPANDING INJECTING DRUG USER EPIDEMIC IN CHINA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 356) Yutaka Takebe1, Y Ma1, C Yang1, S Kusagawa1, Y Yokota1, Y Hoshina1, X Xia2, and K Ben2 Diverse forms of URF are evolving in the western part of Yunnan Province. The similarity of the recombinant structure of Dehong URF and CRF07/08_BC suggests that western Yunnan Province is a birthplace of the presumed ancestor(s) of the HIV strain that has caused the explosive epidemic among IDU in northwestern and southeastern China. |
| 357 | IDENTIFICATION OF NOVEL INTER-CRF RECOMBINANTS BETWEEN CRF07_BC AND CRF01_AE IN MYANMAR: EVIDENCE FOR THE DIRECT INFLUENCE OF CHINA'S INJECTING DRUG USER EPIDEMIC Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 357) Yutaka Takebe1, Y Yokota1, X Li1, S Kusagawa1, Y Hoshina1, T Onogi1, Q Wang1, K Notomi1, T Aung2, K Y Oo2, and M Thwe2 The mixing of different lineages of HIV-1 strains in highly exposed populations leads to the evolution of new forms of HIV-1 recombinants and even the second generation inter-CRF recombinants between previously established CRF. Inter-CRF recombinants (ICR) between CRF01_AE and CRF07_BC identified in the present study represents the second case of this category (ICR between CRF07 and CRF08 was previously identified in Yunnan, China). |
| 358 | EMERGENCE OF HIV-1 CRF01_AE/B UNIQUE RECOMBINANT FORMS IN KUALA LUMPUR, MALAYSIA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 358) Kok-Keng Tee, C K Pon, A Kamarulzaman, and K P Ng Protease and RT genes can be utilized for subtypes/CRF assessment with high degree of agreement, allowing concurrent surveillance of circulating HIV-1 subtypes with antiretroviral drug- resistance genotyping tests. The emergence of highly identical CRF01_AE/B intersubtype recombinants suggests the possibility of the appearance of a new candidate of circulating recombinant form in Kuala Lumpur. |
| 359 | IDENTIFICATION OF DIVERSE PHYLOGENETICALLYY RELATED HIV-1 BG INTERSUBTYPE RECOMBINANT VIRUSES IN CUBA, INCLUDING A NOVEL CIRCULATING RECOMBINANT FORM (CRF20_BG) Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 359) María Sierra1, L Pérez2, M Thomson1, E Delgado1, G Casado1, and R Nájera1 HIV-1 BG recombinant viruses with diverse mosaic structures, grouping in 3 phylogenetic clusters, have been identified in Cuba. All of them derive from B and G subtype strains circulating in Cuba, and have a common ancestry, as inferred from phylogenetic trees and analyses of mosaic structures. Near full-length genome analysis from 3 epidemiologically unlinked viruses from one of the clusters, showing identical structures, defines a novel CRF (CRF20_BG). The 2 remaining clusters are also candidates for novel CRF, pending analyses of additional near full-length sequences. |
| 360 | IDENTIFICATION AND CHARACTERIZATION OF CRF02_AG AND CRF09_cpx RECOMBINANT SUBTYPES IN MALI Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 360) O Koita1, D Dabitao1, S Dao1, M Ibrah1, D Sogoba1, J Warfield2, J Washington3, R Hengel3, H Lane3, M Polis3, A Tounkara1, H Imamichi2, and The Project Serefo In Mali, a large number of the subtype A viruses appear to be recombinant forms, some of which appear to have undergone additional rounds of recombination to produce more complex CRF Creation of new recombinant forms has serious consequences in future vaccine development, diagnostics, and treatment strategies. Thus, the actual and future role of these recombinant viruses in the global pandemic must be monitored in new molecular epidemiological studies. |
| Session 69—Poster Abstracts Molecular Epidemiology: Selection and Evolution |
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| 361 | EPIDEMIOLOGY OF HIV-1 CO-RECEPTOR USAGE: ASSOCIATION OF CXCR4 USE WITH CD4 COUNT, CCR5 Δ32 GENOTYPE AND HIV V3 SEQUENCE IN ANTIRETROVIRAL-NAÏVE INDIVIDUALS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 361) Zabrina Brumme1, J Goodrich2, C Brumme1, B Henrick1, B Wynhoven1, P Cheung1, J Asselin1, R Hogg1, J Montaner1, and P Harrigan1 Baseline CD4 count, pVL, HIV V3 sequence, and CCR5 Δ32 genotype were the strongest determinants of CXCR4-using HIV in this population. The association between CCR5 Δ32 and CXCR4 use suggests that decreased target cell availability of CCR5 may select for X4 variants. These observations may be of relevance to the use of CCR5 antagonists as antiretroviral agents. |
| 362 | HLA B57/5801 ESCAPE MUTATIONS IN HIV-1 GAG DO NOT INFLUENCE THE CLINICAL COURSE OF INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 362) Marjon Navis1, N Kootstra1, T van der Vorst1, D van Baarle2, J Borghans2, F Miedema2, and H Schuitemaker1 In this study we show that viral evolution associated with an HLA B57/5801-directed immune response is present in both typical progressors and slow progressors. Because the escape mutations are observed in both normal and slow progressors, the clinical relevance of these mutations is unproven. |
| 363 | FOOTPRINTS IN SNOW? ANALYZING HOST VS POPULATION SELECTION IN HIV SEQUENCES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 363) Sergei Kosakovsky Pond1, S Frost1, D Richman1,3, and A Leigh Brown2 A high proportion of amino acid substitutions in HIV sequences are phylogenetically recent. This suggests that adaptations to individual hosts are often deleterious and do not persist at the population level, thus the “immunological footprint” may often be ephemeral. This approach provides a rapid, general, and efficient method for testing for differential selective impact on HIV sequences (e.g., in candidate vaccines) without requiring HLA typing of target populations. |
| Session 70—Poster Abstracts Molecular Epidemiology: Linkage |
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| 364 | CAN EPIDEMIOLOGIC LINKAGE IN CHRONICALLY HIV-1-INFECTED COHORTS BE ESTABLISHED? Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 364) M Mikhail1, B Wang1, P Lemey2, B Beckholdt3, A M Vandamme2, M Gill3, and Nitin Saksena1 HIV transmission in chronically infected cohorts can only be proven unambiguously through full-genome HIV sequences. |
| 365 | COMPLEX STRUCTURE OF HIV-1 TRANSMISSION WITHIN LOCALIZED RISK GROUPS REVEALED BY MOLECULAR EPIDEMIOLOGICAL APPROACHES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 365) Stéphane Hué1, D Pillay1, J Clewley2, and O Pybus3 For the first time, we characterized separate sub-epidemics of HIV-1 within a defined risk group, dating the introduction of epidemiologically significant viral lineages and estimating their rates of spread. The results are similar to those identified within the U.S. epidemic. Our study provides new insights into the complexity of HIV-1 epidemics that must be considered when developing HIV monitoring and prevention initiatives, and is applicable to other transmission groups and geographic regions. |
| Session 71—Poster Abstracts Molecular Epidemiology: Diversity of Specific Genes |
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| 366 | COMPREHENSIVE EVALUATION OF HIV-1 INTEGRASE GENE DIVERSITY IN GROUP M, N, AND O VIRUSES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 366) John Hackett, Jr, P Swanson, B Harris, V Holzmayer, J Yamaguchi, P Bodelle, C Brennan, G Schochetman, and S Devare Although HIV-1 is characterized by exceptional genetic diversity, the integrase gene is well- conserved across HIV-1 groups and subtypes. Sequence information from this large set of genetically and geographically diverse strains enhances our understanding of the range and nature of polymorphisms within integrase and may aid development of novel therapeutic agents. Moreover, it will provide a foundation for assessing differences in pathways of evolution of resistance-associated mutations between subtypes/groups of HIV-1. |
| 367 | NEW INSIGHTS IN HTLV-I PHYLOGENY BY SEQUENCING AND ANALYZING THE ENTIRE ENVELOPE GENE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 367) S Capdepont1, D Londos-Gagliardi1, M Joubert2, P Corrèze1, M E Lafon1, B Guillemain1, and Hervé Fleury1 Central African, Indonesian, and Melanesian human and simian isolates could have emerged from a common ancestor closely related to those of Central Africa. Negrito residence in the Andaman Islands could explain HTLV-I migration from Central Africa to eastern parts of Europe and the close origin of Asian and African PTLV-I phylums. Migrations from West Africa could explain the presence of Cosmopolitan strains in Central Africa. The new Maroni subtype may originate from Dutch Guiana fugitive slave descendents. Its relatedness to Cosmopolitan and Central African subtypes suggests a recombination event. Partial env sequences were significantly less informative and justify a full-length env gene analysis for HTLV-I phylogenetic studies. |
| Session 72—Poster Abstracts Molecular Epidemiology: Regional Characteristics |
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| 368 | THE HIDDEN HIV-1 EPIDEMIC IN QUEBEC: RAPID INTRODUCTION OF WILD-TYPE AND NON-B VIRAL-SUBTYPE INFECTIONS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 368) Bluma Brenner1, B Spira1, D Moisi1, R Turgel1, M Roger2, M Ntemgwa1, F Doualla-Bell1, D Turner1, J P Routy1, H Charest3, M Wainberg1, and the Quebec HIV Drug Resistance/Molecular Epidemiology Group This study shows that non-B viral subtypes and new treatment paradigms are the major epidemiological determinants of the new wave of the HIV-1 epidemic in Quebec. The evolution of the HIV-1 epidemic may be masked if data do not exclude multiple genotypic analyses. |
| 369 | CHARACTERIZATION OF FULL-LENGTH HIV-1 GENOME FROM RECENTLY INFECTED SUBJECTS IN BRAZIL Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 369) Dercy Sa-Filho1, M Janini1, R Diaz1, S Sanabani2, E Sabino2, K Bassichetto3, F Mesquita3, and E Kallas1 It is important to survey the genetic diversity of newly transmitted HIV-1 to enable projections of future trends in the local epidemics. Our results show an increase in viral diversity, which may impact future vaccine designs. |
| 370 | INTRODUCTION OF DIFFERENT GENETIC SUBTYPES OF BLOOD-BORNE VIRUSES IN SPAIN BY RECENT IMMIGRANT POPULATION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 370) C Toro1, Sylvina Bassani1, V Jiménez1, C Rodríguez2, J del Romero2, Á Holguín1, A Álvarez1, N Camino1, P Ríos1, C Gómez3, A Guelar4, B Rodés1, and V Soriano1 The rate of HIV-1, hepatitis B, and C infections is low among immigrants to Spain, including populations admitting risky practices. However, the presence of HIV-1 non-B subtypes, HBV genotype E, HCV genotype 4, and HTLV-I in this population represents a unique source of new viral variants in Spain and may have clinical and public health consequences. |
| 371 | FIRST IDENTIFICATION OF HIV-1 GROUP M AND GROUP O DUAL INFECTIONS OUTSIDE OF AFRICA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 371) D Brand1, A Beby-Defaux2, M Macé3, S Brunet1, A Moreau1, C Godet2, X Jais3, F Cazein4, C Semaille4, and Francis Barin1 This is the first identification of HIV-1 group M/O dual infections outside the African continent. Such dual infections may lead to the emergence of HIV-1 M/O recombinant strains as reported in Cameroon, which would be undetectable by virus load assays, naturally drug-resistant, and responsible for subepidemics such as those related to group M circulating recombinant forms. |
| 372 | UNDERSTANDING THE CURRENT HIV-1 EPIDEMIC IN THE ENTIRE YUNNAN PROVINCE OF THE PEOPLE’S REPUBLIC OF CHINA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 372) Y Zhang1, L Lu1, L Ba2, L Yang1, M Jia1, Y Shi1, W Yan1, G Chang1, D Ho2, and Zhiwei Chen2 We have mapped the HIV-1 genotypes in the entire Yunnan province. In particular, the finding of the large number of A/E viruses may indicate new trends of HIV-1 epidemic in Yunnan. Our data provide critical detailed information to guide future HIV-1 prevention and vaccine development efforts in this region. |
| 373 | HIV INFECTION AMONG PREGNANT WOMEN IN RURAL BURKINA FASO Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 373) Denis Tebit1, J Ganamé2, B Coulibaly2, S Tchatchou1, B Kouyaté2, T Boehler1, and H G Kraeusslich1 The HIV prevalence of 4% among pregnant women in this rural area is relatively low compared to 5.2% observed in urban areas. CRF02.AG, and not CRF06.cpx, is the dominant virus circulating in this area. The absence of major drug resistance mutations in naïve subjects and the availability of virological data from this study will support the planned introduction of antiretroviral therapy in this rural area of Burkina Faso. |
| Session 73—Poster Abstracts Neuropathogenesis: Virology |
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| 374 | A RARE AND EXTREME ETIOLOGY OF HIV-1 IN THE CEREBROSPINAL FLUID AND BLOOD IN AN HIV-INFECTED NON-PROGRESSOR Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 374) Bin Wang1, M Mikhail1, W Dyer2, J Zaunders3, D Cooper3, A Kelleher3, B Brew4, and N Saksena1 The CSF may behave as a distinct viral compartment, which may not depend on disease stage. Importantly, the high CD4+ and CD8+ T-cell counts and below-detection plasma viremia may not protect against neurologic symptoms in some cases. HIV-infected non-progressors should opt for lumbar puncture examination. |
| 375 | PHYLODYNAMIC ANALYSIS OF HIV-1 IN THE BRAIN Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 375) M Salemi1, S Lamers2, S Yu3, T de Oliveira4, W Fitch5, and Michael McGrath3 In this case study, viral infection in the brain progressed with a non-specific genetic evolution, recurrent migration events, and an expansion of macrophage tropic sequences. The data suggest that after immune failure newly produced viral variants, which would be rapidly cleared in normal conditions, begin to productively infect macrophages in a self-amplifying cycle of infection and inflammatory response that could contribute to HIV-associated dementia pathogenesis. |
| 376 | A GENETIC VARIANT OF HIV WITH REDUCED CD4 DEPENDENCE IS ASSOCIATED WITH BRAIN INFECTION AND HIV-ASSOCIATED DEMENTIA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 376) Rebecca Dunfee1, E Thomas1, P Gorry1, J Taylor2, K Kunstman2, J Bell3, S Wolinsky2, and D Gabuzda1 N283 is a single amino acid change in gp120 that contributes to reduced CD4 dependence and HIV neurotropism. This genetic variant is found more frequently in brain compared to non-brain tissues, suggesting N283 may confer a selective advantage for HIV replication in the brain. These results provide a better understanding of mechanisms that underlie HIV neurotropism. |
| 378 | ASTROCYTES CONSTITUTE A UNIQUE CENTRAL NERVOUS SYSTEM HIV RESERVOIR IN PERSONS WITH SUPPRESSED PLASMA VIRUS AND ELEVATED CD4+ CELL COUNTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 378) Nikilyn Kinzel1 and W Cavert2 This preliminary data suggests central nervous system infection with HIV is present before development of AIDS and persists after immune reconstitution is achieved despite suppression of plasma viremia by antiretroviral drugs. X4 viral DNA is present in astrocytes; this may indicate these cells are a discrete central nervous system viral reservoir. |
| 379 | ESTABLISHMENT OF PERSISTENT INDUCIBLE LATENT HIV INFECTION IN ASTROCYTES: RELEVANCE TO THE HIV RESERVOIR IN BRAIN Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 379) Ashok Chauhan, S Gartner, and A Nath HIV infection in astrocytes is restricted at the level of viral entry. Low-level infection can occur and lead to establishment of a latent viral state susceptible to the induction of virus expression, and transmission of the infection. |
| 380 | REGULATION OF HIV-1 TRANSCRIPTION BY NF-κB, SP-1, AND HISTONE ACYTELATION IN PRIMARY HUMAN ASTROCYTES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 380) Elena Paskaleva, D Avram, and M Canki These results demonstrate that in vitro, primary human astrocytes are productively infected by HIV-1, leading to a gradual decline and basal low-level viral replication. The fact that levels of NF-κB did not change considerably throughout infection indicates continuous involvement of NF-κB in HIV-1 transcription. In contrast, a 4-fold decrease in SP-1 on day 30 post-infection suggests an active role for SP-1 in down-modulation of viral transcription. A 1.7-fold decrease in Ac-H4 at the nadir of infection confirms the overall decrease in transcriptional activity, as well as implies a possible nucleosome rearrangement on the LTR promoter. The overall decline in transcription correlates well with a decrease in p24 levels and percentage of positive cells on day 30 post-infection. |
| 381 | MOLECULAR MECHANISMS FOR HIV-1 RESTRICTION IN HUMAN ASTROGLIA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 381) Roger Pomerantz, J Fang, E Acheampong, and M Mukhtar As such, it is suggested that a Rev-deficient phenotype is demonstrable through complementary techniques in certain human fetal astrocytes and that the newly described Rev binding protein, DDX1, may be critical in explaining the molecular mechanisms behind this novel state of viral restriction and possibly a site for reservoir disease during therapy. |
| 382 | HIV-1 NEF POTENTLY INDUCES APOPTOSIS AT THE BLOOD-BRAIN BARRIER Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 382) Roger Pomerantz, E Acheampong, Z Parveen, L Muthoga, M Kalayeh, and M Mukhtar The results of this study demonstrate that Nef likely contributes to the neuroinvasion and neuropathogenesis of HIV-1, through its effects on select cellular processes, including various apoptotic cascades. |
| 383 | POTENTLY TARGETING NEUROTROPIC HIV-1 STRAINS WITH RNA INTERFERENCE IN HUMAN MACROPHAGES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 383) Rajnish S Dave and R Pomerantz The conservation of each of these targets in the above mentioned viral strains, as well as several primary isolates, would enable these siRNA to be used as potent antiviral tools for investigations in cells derived from the central nervous system. The sustained ability of these siRNA to limit HIV-1 infection in macrophages makes them effective tools to evaluate their therapeutic potential, and assess their utility in inhibiting HIV-1 neuropathogenesis and neuroinvasion. |
| 384 | ENHANCED REPLICATION OF HUMAN POLYOMAVIRUS JC TYPE 2B IN PRIMARY GLIAL CELLS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 384) Vivek Nerurkar1, R Frisque2, T Bui1, and S Tyagarajan2 Based on the in vitro data and the published in vivo data, we conclude that unique sequences in JCV type 2B coding region (early and/or late proteins) confer enhanced replication potential. Identification of these unique sequences would lead to a better understanding of the disease, to the development of diagnostic tests to facilitate clinical observations, and to the opening of roads to effective treatments. |
| Session 74—Poster Abstracts Neuropathogenesis: Host Co-Factors |
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| 385 | PROMYELOCYTIC LEUKEMIA PROTEIN CONTRIBUTES TO THE NON-PERMISSIVE ASTROCYTIC INFECTION BY HIV Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 385) David Galey, A Chauhan, G Hayward, and A Nath Endogenously high levels of PML in astrocytes as compared with permissive cell types contribute to the non-permissive nature of HIV infection in astrocytes. This is accomplished at both the pre-integration level and by repressing LTR activity, likely by interfering with Tat transactivation. |
| 386 | A QUANTITATIVE AND TOPOGRAPHIC ANALYSIS OF NEUROGLIAL REACTIONS IN HIV DEMENTIA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 386) Adrea Lee1, D Vargas1, C Nascimbene1,2, L Guo1, J Williams3, and C Pardo1 This study supports the hypothesis that marked microglia activation in the brain is a commonly seen reaction in the central nervous system of patients with AIDS, but it did not establish differences in neuroglial activation between HIV+D and HIV+ND patients. Even though there is no evidence of neuroglial proliferation HIV+ cases, astrocytes in HIV+D and HIV+ND had morphological evidence of activation. These findings support the central role of neuroglial activation and dysfunction in neurological complications of AIDS such as HIV+D. |
| 387 | EFFECT OF HIV-1 PRIMARY ISOLATES ON MONOCYTE PROTEOME AND NEUROVIRULENCE FROM HISPANIC WOMEN WITH COGNITIVE IMPAIRMENT Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 387) Dianedis Toro1, E Anderson1, M Plaud1, E Rodríguez1, V Wojna1, P Ciborowski2, H Gendelman2, and L Meléndez1 The viral tropism of the blood HIV-1 isolates did not correlate with dementia in these patients. The down-regulation of the 11313.08 M/Z peak in MDM infected with HIV-1 isolates from demented patients may play a role in the development of HIV-associated dementia. |
| 388 | MECHANISMS OF HIV-INDUCED NEURODEGENERATION: ROLE OF NMDA RECEPTOR SUBTYPES IN COMMUNICATING NEURONAL CELL DEATH Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 388) Lauren A O'Donnell1, A Agrawal1, D Lynch1,2, M Dichter1, and D Kolson1 NMDA receptors play a significant role in HIV-induced neurodegeneration in our model, and susceptibility follows known NMDA receptor subunit expression patterns. Immature neurons (with lower NMDA receptor expression) are resistant, while mature neurons are susceptible to HIV-induced neurodegeneration. Antagonists of the NMDA receptor-2B subunit, which predominates in developing neurons, completely protect neurons at 14 days in vitro, but only partially protect at 21 days in vitro. This change in neuronal susceptibility may reflect increasing expression of NMDA receptor-2A in maturing hippocampal neurons. We are currently dissecting the role of NMDA receptor-2A in this process. Understanding the role of NMDA receptors subtypes in neurodegeneration may reveal new therapeutic targets. |
| 389 | TRAIL CONDITIONALLY INDUCES APOPTOSIS IN HUMAN NEURAL PROGENITOR CELLS: LINKAGE TO THE PATHOGENESIS OF HIV-1-ASSOCIATED DEMENTIA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 389) Hui Peng, Y Huang, A Lopez, D Xu, A Ghorpade, and J Zheng TRAIL is significantly up-regulated in HAD. However, our results suggest that human neural progenitor cells are resistant to TRAIL-mediated apoptosis, possibly due to highly expressed IAP proteins, such as cIAP1, in this specific cell population. |
| 390 | EXOGENOUS IL-7 INDUCES NEURONAL APOPTOSIS: MOLECULAR MECHANISMS DURING HIV-1 INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 390) Yan Xu, E Acheampong, R Daniel, J Fang, C Zhang, M Mukhtar, G Nunnari, and R Pomerantz Our data suggest, in contrast to the potential positive roles of IL-7 in immune-antiretroviral HIV-1 therapy, that IL-7 could cause neuronal programmed cell death via Fas and TNF pathways, both during therapy and via endogenous secretion during AIDS. |
| 391 | STATINS BLOCK ENHANCED TRANSVASCULAR MIGRATION OF HIV-1-INFECTED CELLS: A NOVEL THERAPEUTIC APPROACH FOR HIV-1 NEUROINVASION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 391) Muhammad Mukhtar1, A Mengistu2, E Acheampong1, J Sullivan1, G Nunnari1, E Argyris1, M Kalayeh1, K Williams1, and R Pomerantz1 Thus, prevention of enhanced transmigration of HIV-1-infected cells with statins could potentially be of benefit by 2 mechanisms: limiting AIDS-related neuropathologies, and controlling establishment of HIV-1 reservoirs in the brains of infected individuals. |
| 392 | GENE EXPRESSION IN CEREBRAL ENDOTHELIAL CELLS TREATED WITH THE HIV PROTEASE INHIBITOR INDINAVIR Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 392) Aline Grigorian, R Hurford, Y Chao, C Patrick, and D Langford These results indicate that exposure of cerebral endothelial cells to INV affects signaling events that may affect downstream signaling pathways and could contribute to patient responses to HAART or to the patterns of central nervous system/ blood–brain barrier damage observed in the HAART-adherent patient. |
| 393 | HIV-1-INFECTED MACROPHAGES CAUSE MITOCHONDRIAL IMPAIRMENT IN HUMAN DORSAL ROOT GANGLIA NEURONAL CULTURES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 393) Katrin Hahn, B Robinson, C Anderson, D Galey, S Gartner, and A Nath We describe an in vitro model for HIV-peripheral neuropathy in which supernatant from HIV-1-infected macrophages caused toxicity to human dorsal root ganglia neurons resulting in mitochondrial toxicity and neurite retraction without significant cell death. Thus antioxidants may have a therapeutic potential in patients with HIV-associated peripheral neuropathy. |
| 394 | NEUROPATHOGENIC EFFECTS OF HIV-1 ON DORSAL ROOT GANGLION NEURONS: PRO-INFLAMMATORY CYTOKINE INDUCTION AND NEURONAL DEGENERATION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 394) G Jones1, Y Zhu1, S Tsutsui1, J McArthur2, C Pardo2, O Keppler3, and Christopher Power1 Our results suggest that HIV-1 infection of the peripheral nervous system causes neuronal degeneration, possibly through an indirect mechanism mediated by Schwann cell activation and pro-inflammatory cytokine (e.g., TNF-α and/or IL-1β) production by peripheral nerve resident macrophages. |
| 395 | IN VITRO MODELS OF HIV-ASSOCIATED NEUROPATHIES DIFFER IN PATHOGENIC SITE OF ACTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 395) Giorgia Melli and A Hoke This study shows that although distal symmetric polyneuropathy and antiretroviral toxic neuropathy are similar to each other clinically and pathologically, the sites of action of gp120 and ddC, agents that model distal symmetric polyneuropathy and antiretroviral toxic neuropathy, respectively, are different. These studies suggest that strategies directed toward protection of the axons might be more fruitful in diseases where the primary action is at the axonal level, rather than the cell body level. |
| 396 | DEVELOPMENT OF A SMALL RODENT MODEL OF HIV-ASSOCIATED SENSORY NEUROPATHIES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 396) C Jack, C Zhou, G Melli, S Keswani, and Ahmet Hoke This animal model combines the neurotoxic effects of high levels of gp120 in the endoneurium and exposure to ddI, a NRTI known to cause peripheral neuropathy in patients. Using this animal model we will be able to study pathogenic mechanisms and contribution of each to the axonal degeneration in detail. Furthermore, we will use this animal model to screen for drugs that are promising as neuroprotective agents in our in vitro assays. |
| Session 75—Poster Abstracts Neuropathogenesis: Therapy and Clinical Studies |
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| 397 | HIV Neuropathy Natural History Cohort Study: Clinical and Laboratory Features, and Risk Factors for Progression: ACTG A5117 Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 397) David Simpson1, S Evans2, D Kitch2, J McArthur3, D Asmuth4, B Cohen5, K Goodkin6, C Shikuma7, J Weigh7, Y So8, C Marra9, R Diaz-Arrastia10, L Millar11, S Shriver12, D Clifford13, and ACTG A5117 Study Group Peripheral neuropathy remains highly prevalent in HIV infection, and its course was relatively stable over 48 weeks. Previously established risk factors for peripheral neuropathy, including CD4 and HIV RNA, were not predictive for the presence or progression of neuropathy. While use of d-drugs did not predict progression of peripheral neuropathy, these results should be interpreted with caution due to possible acquisition bias. |
| 398 | ACTG 5117 HIV-ASSOCIATED SENSORY NEUROPATHY COHORT: ANALYSIS OF EPIDERMAL NERVE FIBER DENSITIES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 398) L Zhou1, P Hauer2, D Kitch3, Justin McArthur2, M Gerschenson4, C Marra5, D Clifford6, V Valcour4, R Diaz-Arrastia7, L Millar8, S Shriver9, B Cohen10, Y So11, S Evans3, D Simpson12, and ACTG Neurological complications group ENFD correlated significantly with total neuropathy score and neuropathic pain measures at baseline, and were stable over time. ENFD did not predict transitions, or levels of neuropathic pain. |
| 399 | PERIPHERAL NEUROPATHY AND OXIDANT STRESS DURING ART: NWCS230, AN ANALYSIS OF ACTG STUDY 384 Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 399) Todd Hulgan1, J Morrow1, X Sun2, M Hughes2, L Smeaton2, E Terry1, G Robbins3, R Shafer4, D Clifford5, G McComsey6, J Canter1, D Haas1, and the ACTG Study 384 Team Plasma F2-IsoP levels were unexpectedly high at baseline in cryopreserved specimens from these study subjects compared to levels from a previous study that included HIV-infected adults not receiving ART. This may reflect ex vivo auto-oxidation of some plasma specimens. Although F2-IsoP increases tended to be somewhat greater in ddI/d4T recipients than in ZDV/3TC recipients, we did not detect significant associations between F2-IsoP and development of symptomatic peripheral neuropathy. Further studies in this area are warranted. |
| 400 | ALCOHOL AND INJECTION DRUG USE DOES NOT INFLUENCE EPIDERMAL NERVE FIBER DENSITIES IN SUBJECTS EXPOSED TO DIDEOXYNUCLEOSIDE ANALOGS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 400) Anita Venkataramana, R Skolasky, J Creighton, S Raman, and J McArthur Too few skin biopsies were taken to make a valid statistical correlation, but performed at 48 weeks may be a better correlate of dideoxynucleoside use and epidermal nerve fiber density. A statistically significant correlation was found between CD4 cell count and proximal thigh epidermal nerve fiber density. No statistically significant associations can be made between alcohol or IDU and epidermal nerve fiber density at the distal leg and proximal thigh. |
| 401 | LONG-TERM EFFECT OF HAART ON INTRATHECAL HIV-1 REPLICATION DESPITE SYSTEMIC VIRO-IMMUNOLOGICAL FAILURE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 401) S Palmieri, L Galli, R Pedale, A Bestetti, S Sala, A Lazzarin, and Paola Cinque HAART seems to maintain its efficacy on intrathecal virus replication in long-term treated patients irrespective of poor systemic viro-immunological responses. |
| 402 | ENFUVIRTIDE CEREBROSPINAL FLUID PHARMACOKINETICS: A POTENTIAL TOOL TO ANALYZE CSF HIV ORIGIN AND THE THERAPEUTIC ROLE OF LOCAL DRUG PENETRATION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 402) Richard W Price1, R Palmatier2, S Wring2, J Lu3, B Baker2, J Sailstad2, N Lollo1, S Spudich1, R Hoh1, T Liegler1, D Miralles2, D Kuritzkes3, and S Deeks1 ENF CSF penetration is negligible. However, since CSF infection often results from transitory mechanisms with transfer of virus and T cells from blood to CSF, ENF may help to control CSF HIV indirectly through effects on systemic infection. Because of its poor penetration and its unique site of action and associated mutational markers of resistance, ENF provides a tool to dissect the origin of CSF virus and explore the therapeutic settings where drug penetration is or is not important. |
| 403 | KALETRA INDEPENDENTLY REDUCES HIV REPLICATION IN CEREBROSPINAL FLUID Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 403) G van den Brande1, J Marquie-Beck1, E Capparelli1, R Ellis1, A McCutchan1, A Hermes2, M Buzzell1, and Scott Letendre1 This study is novel because it used sequential introduction of ARV to determine whether a highly protein-bound PI can reduce HIV replication in the central nervous system. LPV/r alone reduced HIV RNA in CSF after just 3 weeks, proving that it contributes to control of HIV replication in the brain when used in combination with other ARV and suggesting that it may benefit patients diagnosed with or at risk for HAD. |
| 404 | META-ANALYSIS OF CIDOFOVIR IN AIDS-RELATED PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY ON HAART: SURVIVAL AND NEUROLOGICAL OUTCOME Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 404) Andrea De Luca1, P Pezzotti2, J Gasnault3, P Cinque4, J Berenguer5, S Di Giambenedetto1, A Cingolani1, Y Taoufik3, R Pedale4, P Miralles5, D Larussa6, S Sinha7, C Marra7, A Ammassari1, A Antinori6, and for Gesida 9/99, IRINA and AACTG 363 Study Groups In a metaanalysis of HIV+ HAART-treated PML, CDV was significantly associated with improved survival when follow up was started from PML diagnosis, but not when it started at time of CDV initiation. Moreover, CDV use did not influence severity of disability. New treatments for PML are urgently needed. |
| Session 76—Poster Abstracts Neuropathogenesis: Clinical Correlates and Observational Studies |
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| 405 | RELATIONSHIP OF ANTIRETROVIRAL TREATMENT DURING LIFE TO POST-MORTEM BRAIN TISSUE VIRAL LOAD IN HIV-INFECTED PATIENTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 405) D Langford, J Marquie-Beck, S de Almeida, D Lazzaretto, Scott Letendre, I Grant, A McCutchan, E Masliah, and R Ellis These findings suggest that HAART is partially effective in suppressing central nervous system viral replication. Strategies for optimizing central nervous system viral inhibition will be important for managing HIV central nervous system disorders, including HIV dementia and milder neurocognitive impairment, and might help to prevent the development of antiretroviral drug resistance. |
| 406 | EVIDENCE FOR VIRUS-SPECIFIC IMMUNE RESPONSE IMBALANCE IN HIV-ASSOCIATED LEUKOENCEPHALOPATHIES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 406) Serena Delbue1, M Saresella1, E Colombo1, F Guerini1, M Valli1, I Marventano1, M Zanzottera1, R Mancuso1, G Sotgiu2, R Maserati3, and P Ferrante1,4 No virus has been found in NDLE samples, however, the JCV-specific immune response observed in PML and in NDLE patients suggests that, also in NDLE, JCV could play a role yet to be defined. The finding of an increased cytotoxic activity indicates that an immune mediated mechanism is probably relevant in NDLE pathogenesis. |
| 407 | Brain Activation during Working Memory as an Outcome Measure for Treatment of HIV-associated Cognitive Impairment Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 407) Christina Marra, T Richards, K Field, A Parsons, D Lockhart, C Dodrill, M Perrin, A Collier, and E Aylward As with neuropsychological tests, functional MRI shows a learning effect for controls. While HAART may result in improved brain function, sustained control of plasma viremia for > 8 weeks may be required to demonstrate this by functional MRI or neuropsychological tests. |
| 408 | PERIPHERAL HIV-1 DNA COPY NUMBER AND HIV-1-ASSOCIATED DEMENTIA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 408) Bruce Shiramizu1, S Gartner2, A Williams1, C Shikuma1, S Ratto-Kim1, M Watters1, and V Valcour1 These findings suggest a potentially important association between circulating provirus and HAD. |
| 409 | DORSAL ROOT GANGLIA ARE THE MOST CONSISTENT FINDING IN THE PATHOLOGY OF SENSORY PATHWAYS IN HIV NEUROPATHY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 409) Caterina Nascimbene1,2, D Vargas1, P Hauer1, L Guo1, J Williams1, and C Pardo1 The findings of this study support the view that the dorsal root ganglia is the main site of dysfunction in sensory pathways of patients with HIV+SN. The presence of marked increase in macrophage activation and infiltration of the perineuronal compartment in the dorsal root ganglia may play a role in neuronal dysfunction and explain some of the features of painful sensory symptomatology in HIV+SN. |
| 410 | Evidence of HIV-1 Infection of Nestin-positive Neural Progenitor Cells in Archival Pediatric Brain Tissue Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 410) Lynnae Schwartz1, D Lawrence1, W Cavert2, L Civitello3, N Kinzel4, R Chandra3, and E Major1 This is an ongoing study of archival pediatric brain tissue to identify neural progenitor cells as targets for HIV-1, as suggested by cell culture data. The pathophysiological consequences of HIV-1 infection of neural progenitor cells in the developing pediatric brain must be determined because it is possible that HIV-associated alterations in neural progenitor cell function could contribute to the unique neuropathology of pediatric AIDS, including decreased brain growth, cognitive impairment, and poorly modulated responses to HIV-associated inflammatory brain injury. |
| 411 | MCP-1 LEVELS AND CCR2 EXPRESSION OF MONOCYTES IN CEREBROSPINAL FLUID OF HIV-1-INFECTED INDIVIDUALS ON AND OFF ANTIRETROVIRAL THERAPY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 411) Jutta K Neuenburg1, N Lollo2, R Grant1, and R Price2 These observations are consistent with a role for CCR2 and its ligand MCP-1/CCL2 in trafficking of monocytes into CSF of HIV-infected patients on and off ART including PI. Increased permeability of the blood–brain barrier in viremic patients may contribute to enrichment of CCR2+ monocytes in CSF of untreated patients. The majority of monocytes in CSF are CCR2–, suggesting that other chemokine receptors may be involved or that CCR2 expression is down-regulated. |
| 412 | CD14+/CD16+ MONOCYTES ARE ENRICHED IN CEREBROSPINAL FLUID OF HIV-1-INFECTED INDIVIDUALS ON PROTEASE INHIBITORS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 412) Jutta K Neuenburg1,2, N Lollo2, R Price2, and R Grant1,2 PI-use might lead to changes in plasma LDL without overt lipidemia that can activate monocytes, leading to trafficking of activated monocytes into tissues, among them CSF. Alternatively, monocyte trafficking to the CSF, and possibly CNS, may be an immune response to HIV-infection in brain tissue that persists despite ART. |
| 413 | INDIVIDUALS AT RISK FOR HIV-1 DEMENTIA EXPRESS ELEVATED SIALOADHESIN (CD169) ON THEIR CIRCULATING MONOCYTES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 413) Lynn Pulliam1, B Sun1, and H Rempel2 Circulating CD14+ monocytes from individuals with high viral load have an elevated macrophage marker of chronic inflammation. In rheumatoid arthritis and Kaposi’s sarcoma, expression of sialoadhesin has been restricted to macrophages localized at the site of chronic inflammation. We report that sialoadhesin is present on circulating monocytes from subjects with high viral load on HAART as well as perivascular brain macrophages in HIV-1 encephalitis. These results suggest that subjects with high viral load and other risk factors continue to be at risk for HIV-1 dementia. |
| Session 77—Poster Abstracts (and Session 11—Poster Discussion) NK Cells in HIV Infection |
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| 414 | INNATE IMMUNITY IN HIV INFECTION: ENHANCED NATURAL KILLER CELL-DEATH AND TURNOVER MEDIATED BY ALTERED EXPRESSION OF INTERFERON-STIMULATED GENES (ISG) Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 414) Shyam Kottilil1, J Jackson1, T W Chun1, M O'Shea1, M McLaughlin1, J Yang2, R Lempicki2, and A Fauci1 Our data demonstrate that ongoing HIV replication results in profound NK cell abnormalities that are likely to be due to the effects of virus-induced immune activation and increased susceptibility to cell death. Most noteworthy was the increased expression of CD95 and Ki67 correlating with susceptibility of NK cells from HIV-viremic individuals to undergo FMA and increased NK cell turnover. These data are consistent with our previous observations that ongoing HIV replication results in profound NK cell dysfunction and increased susceptibility to cell death. |
| 415 | INVESTIGATION OF NATURAL KILLER CELL FUNCTION AND PHENOTYPE IN HIV LONG-TERM NON-PROGRESSION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 415) Geraldine O'Connor1, A Holmes2, F Mulcahy2, and C Gardiner1 The decrease in NK cell cytotoxicity seen in HIV infection is reduced in HIV LTNP, a group that maintain control of viral replication, suggesting a possible role for NK cells in control of HIV. A number of phenotypic changes in the expression of NK cell receptors were found in both HIV patient groups that may contribute to clinical outcome. |
| 416 | CHRONIC HIV-1 INFECTION LEADS TO A LOSS OF NK CELLS WITH A PREFERENTIAL DEPLETION OF CD56bright NK CELLS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 416) Galit Alter, J Malenfant, N Teigen, and M Altfeld These data demonstrate a preferential loss of CD56bright NK cells in viremic HIV-1 infection, potentially due to a directional differentiation from CD56bright to CD56dim NK cells in the presence of high apoptotic rates in the CD56dim population. |
| 417 | LOW NK CELL NUMBERS ARE ASSOCIATED WITH FAST PROGRESSIVE HIV-INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 417) B Castro Frenzel1, H Heiken1, U Moebius1, S Kovalczik1, S Corey2, K Ulbricht1, M Stoll1, R Schmidt1, S Kalams2, and Dirk Meyer-Olson1 Our data indicate that untreated HIV-infected subjects with low numbers of natural killer cells may have a higher risk for rapid progression of HIV-disease. These data also indicate the prognostic value of NK cell numbers in HIV-infected patients with CD4+ T helper cell counts > 500/μl. Our findings support a role of the innate immune system in the pathogenesis of HIV-infection. |
| 418 | DISCONNECT BETWEEN THE RECOVERY OF NK CELL-MEDIATED CYTOTOXICITY TO HIV-INFECTED TARGETS AND RESTORATION OF NK SUBSETS IN ART-SUPPRESSED HIV-1-INFECTED INDIVIDUALS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 418) Livio Azzoni1, J Chehimi1, M Farabaugh1, S Creer1, K Mounzer2, J Kostman3, C Gallo2, J Ondercin2, J Schull2, and L Montaner1 The rapid reconstitution of cytotoxic activity by NK cells via direct or cytokine and CpG-mediated pathways indicates a quick reversal of a functional block (e.g., by soluble viral proteins tat or gp120) in the absence of full restoration of mature NK subsets upon viral suppression, suggesting that a partial NK-cell subset recovery may be sufficient to quickly restore the full cytotoxic potential once viral suppression is achieved. |
| 419 | NATURAL KILLER CELL NKG2A EXPRESSION IS UNAFFECTED BY SHORT TERM INCREASES IN HIV-1 VIREMIA DURING TREATMENT INTERRUPTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 419) Christopher M Mela1, M Goodier1, C Burton1, N Imami1, M Nelson2, B Gazzard2, and F Gotch1 Patients with long-standing successful suppression of viremia have a greater percentage of NKG2A expressing NK cells than those with detectable HIV-1 plasma virus. Reduction in the proportions of NKG2A+ NK cells in HIV-1 patients is not, however determined by viremia alone, at least in the short term. In contrast, NKG2A-expressing T cells are more sensitive to the presence of HIV-1 and increases in viremia result in a rapid increase in the proportion of these cells. |
| 420 | LONGITUDINAL ANALYSIS AND MODELING IDENTIFIES CHANGES IN INNATE IMMUNITY PARAMETERS AS PREDICTIVE CORRELATES OF CD4 RECONSTITUTION IN ART-TREATED HIV-1 INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 420) Livio Azzoni1, J Chehimi1, R June1, M Farabaugh1, B Thiel1, L Zhou2, and L Montaner1 We identify significant time-dependent changes in innate immune parameters and immune activation following long-term viral suppression, indicating that CD4 recovery is associated with suppression of innate and adaptive immune activation, and with recovery of APC/MLR function. Our results also support the hypothesis that expansion of NK cells subsets during suppressive ART does not depend on their sustained activation. |
| 421 | RETAINED NK AND DC SUBSETS UPON VIRAL REPLICATION FOLLOWING TREATMENT INTERRUPTION IN CHRONICALLY SUPPRESSED HIV-1-INFECTED SUBJECTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 421) Emmanouil Papasavvas1, L Azzoni1, J Chehimi1, B Thiel1, M Pistilli1, M Farabaugh1, A Mackiewicz1, S Creer1, C Gallo2, K Mounzer2, J Ondercin2, J Shull2, J Kostman2,3, and L Montaner1 Viral replication following ART interruption is not associated with a direct impairment of DC and NK cell-mediated responses, but results in rapid activation of NK cells. These findings support the hypothesis that loss of cellular innate immune function in chronically viremic individuals is due to viral-mediated secondary effects and not to direct effects of viral replication. Our data also identify the innate effector cell subsets as potential targets for immunotherapy (i.e., CpG, IFN-γ) shortly after therapy interruption based on their retained number and effector function despite of acute viral replication. |
| 422 | ALTERED NK CELL REPERTOIRE IS DETECTED BY REAL-TIME PCR AND PHENOTYPIC ANALYSIS OF EXPOSED UNINFECTED VIETNAMESE INTRAVASCULAR DRUG USERS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 422) S Ravet1, D Scott-Algara2, E Bonnet1, H Trang3, L Troung3, N Nguyen4, E Vivier5, F Barré-Sinoussi2, G Pancino2, and Pascale Paul1 Analysis of the NK cell repertoire of EU who are protected from HIV infection reveals specific features that may confer activated NK cells with better protective capacities in controlling HIV infection. Although the sample of protected individuals is too small to derive consistent NK receptor patterns of expressed genes associated to EU, altered enhanced representation of some KIR, CD69, CD161, and CD85j is observed in some EU. In particular, as shown previously in relation to AIDS or hepatitis C, selective expansion of KIR3DS1+ or KIR2DL3+ NK cell subsets, detected here by real-time PCR, may represent an advantage for NK cells in better resolving HIV infection in some EU. The functional relevance of enhanced expression of CD85j, CD161, and KIR expression needs to be further assessed. |
| Session 78—Poster Abstracts Dendritic Cell Activation of Antiviral Immunity |
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| 423 | HUMAN DENDRITIC CELLS TRANSFECTED WITH LYSOSOME-TARGETED CHIMERIC NEF PROTEIN INDUCE ACTIVATION AND EXPANSION OF NEF-REACTIVE CD4+ AND CD8+ T CELLS IN VITRO Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 423) Daniel Kavanagh1, D Kaufmann1, S Sunderji1, B Wagner1, D Boczkowski2, E Gilboa2, E Roseberg1, B Walker1, and N Bhardwaj1,3 Transfection of MDDC with lysosome-targeted nef constructs permits efficient presentation of nef-derived antigens in the context of MHC class I and class II. Co-culture of autolgous T cells with chimeric nef-transfected MDDC induced specific expansion of nef-reactive CD4 and CD8 T cells for some patients. The reason other patients’ T cells failed to respond to stimulation by MDDC is a topic of ongoing investigation. Immune therapy with autolgous MDDC-expressing chimeric HIV antigens derived from autologous clinical isolate HIV sequences is a promising method to boost antiviral CD4 and CD8 T-cell responses in chronic HIV patients. |
| 424 | IN VIVO PRIMING OF SIV-SPECIFIC RESPONSES BY AT-2 SIV-LOADED MATURE DENDRITIC CELLS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 424) Vennansha Williams1, I Frank1, J Santos1, J Lifson2, A Gettie3, and M Pope1 These data confirm that mature DC are able to process and present AT-2 SIV for the activation of primary SIV-specific IFN-γ responses in vivo. Targeting antigens to mature DC represents an important way to induce stronger, broad-acting virus-specific immunity in naïve and infected individuals. |
| 425 | DENDRITIC CELL AND CD4+ AND CD8+ T-CELL FUNCTION AMONG HIV-1-INFECTED INDIVIDUALS ON SUPPRESSIVE HAART ACCORDING TO CD4+ CELL NADIR Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 425) P Haslett, O Almeida-Duque, N Shrestha, G Barber, J Zambrano, J Gaitan, and Rafael Campo The timing of HAART has no apparent effect on either recovery of DC subsets or on HIV-, CMV-, or Candida-specific T-cell function. Our data suggest an immune regulatory role of the DC2 subset in limiting pathologic CD8+ T-cell activation and facilitating normalization of the CD4+:CD8+ T-cell ratio. |
| 426 | DENDRITIC CELL REQUIREMENT TO ACTIVATE NK CYTOTOXIC ACTIVITY AGAINST VIRAL INFECTED BUT NOT TUMOR TARGET CELLS IN HIV-1-INFECTED INDIVIDUALS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 426) J Chehimi1, Costin Tomescu1, L Azzoni1, M Farabough1, S Creer1, J Ondercin2, J Shull2, K Mounzer2, J Kostman2, and L Montaner1 Our data indicate that in HIV infection, NK responses against infected targets depend on the presence of both mature NK and functional PDC. Our results support a critical role for HLA-DR+ cells/PDC in regulating NK cell cytotoxic responses against virally infected cells, but not tumor targets, where no evidence of HLA-DR+ cell-mediated help was observed. |
| 427 | IN VIVO ACTIVATION OF LYMPH NODE DENDRITIC CELLS AND B CELLS BY CpG-C ISS-ODN IN NAÏVE AND SHIV-INFECTED MACAQUES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 427) Natalia Teleshova1, J Kenney1, G Van Nest2, J Marshall2, J Lifson3, J Dufor4, R Bohm4, A Gettie5, and M Pope1 C274 effectively activates macaque PDC and B cells within the lymphoid tissues in vivo. This has important implications for the use of CpG-C ISS-ODN to directly boost the cellular functions of resident DC and B cells in vivo to enhance anti-HIV vaccine immunogenicity. |
| Session 79—Poster Abstracts B-cell Responses and Functions |
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| 428 | STABILITY OF HIV-1 ANTIBODY DETECTION IN BODY FLUIDS: IMPLICATIONS FOR MONITORING IN PREVENTIVE VACCINE TRIALS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 428) Julie Elliott, O Yang, J Ibarrondo, M Fuerst, M A Hausner, C Price, J Matud, L Hultin, P Hultin, B Jamieson, and P Anton While HIV-1 antibody levels in plasma and oral mucosal samples were stable over time, the rectal fluids gave highly variable results. This may reflect increased biologic variation within the rectal compartment, although the sample’s increased variation in IgG/IgA may signal variations in technique and/or small amounts of contamination by blood. Orasure® samples may represent a more practical and sensitive approach to monitoring induced mucosal antibody levels in sero-negative vaccine trials. |
| 429 | NEUTRALIZING ANTIBODY PATTERNS AND VIRAL ESCAPE IN HIV-1 SUBTYPE A AND CRF02_AG CHRONICALLY INFECTED TREATMENT-NAÏVE INDIVIDUALS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 429) Halonna Kelly1, M Urbanski2, J Nanfack3, M Tongo3, L Zekeng3, T Kinge4, and P Nyambi1 These results suggest that neutralizing antibodies are readily generated during chronic infection, in a manner independent of the CD4 T-cell level of the host. Thus, consistent with what is seen during acute HIV-1 infection, in clade-B-infected hosts, neutralizing antibodies are readily generated during chronic infection, in non-subtype-B-infected individuals, even at low CD4 T-cell counts, resulting in virus escape and the subsequent emergence of new antibodies to the escape mutants. |
| 430 | NEUTRALIZING ANTIBODY IN HIV-1 PATIENTS WITH CLINICALLY UNDETECTABLE VIRAL LOADS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 430) Justin Bailey, K Lassen, and R Siliciano LTNP have neutralizing antibody against autologous, contemporaneous plasma virus, while HAART-treated patients show weak or absent neutralizing antibody responses against autologous virus. This difference in neutralizing antibody coverage may in part explain the durable suppression of viremia in LTNP and the almost immediate rebound of viremia in HAART patients upon cessation of therapy. |
| 431 | HIV-1 ENVELOPE GLYCOPROTEIN INDUCES APOPTOSIS IN HUMAN B CELLS FROM HIV-1-INFECTED PATIENTS VIA A CASPASE-DEPENDENT PATHWAY WITH RESCUE BY THE CHEMOKINE, SDF-1α Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 431) Christina Nance1 and W Shearer1,2 These data suggest the potential for therapeutic approaches involving SDF-1α to reduce HIV-1-induced B cell apoptosis in HIV-1-infected patients through the CXCR4-caspase-dependent signaling pathway. |
| 432 | B CELLS FROM NAÏVE AND SHIV-INFECTED MACAQUES ARE ACTIVATED BY CpG-C ISS-ODN Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 432) N Teleshova1, Jessica Kenney1, G Van Nest2, J Marshall2, J Lifson3, J Dufor4, R Bohm4, A Gettie4, and M Pope1 Efficient activation of DC by C274, combined with its ability to activate B cells, potentially boosting their antigen-presenting capability, as well as the ability expand antigen-specific B cells, reinforces its potential value as an adjuvant for use with anti-HIV vaccines. The current results suggest that these activities of C274 can usefully be tested in the rhesus macaque model. |
| Session 80—Poster Abstracts ex vivo Analysis of Cellular Responses |
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| 433 | HIV PRODUCTIVE REPLICATION SWITCHES THE CYTOKINE PROFILE OF PRIMARY Th1 AND Th2 CELLS TO THAT OF A Th0 PHENOTYPE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 433) B Bahbouhi, Alan Landay, A Tenorio, and L Al-Harthi Data indicate that HIV-productive replication in Th2 or Th1 cells induces a Th0 phenotype. This may be an inherent result of HIV-mediated potent cell activation or a deliberate mechanism to overcome the skewing of the immune response, the immunologic consequences of which remains to be elucidated. |
| 434 | INTERLEUKIN-2 RECONSTITUTES DEFECTIVE HIV-1- AND CMV-SPECIFIC CD8+ T-CELL PROLIFERATION IN HIV INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 434) Jie Yu1, H Chen1, H Horton2, A Bansal3, J McElrath2, R Reichman1, P Goepfert3, and X Jin1 These results are supportive of the hypothesis that the impairment of CD4 helper cells, including reduced IL-2 production, is a contributing factor to the diminished proliferation of CD8+ T cells. Our results may have implications for the design of immune modulation strategies in vivo. |
| 435 | EX VIVO FUNCTIONAL ANALYSIS OF HIV-SPECIFIC CD4+ T-CELL RESPONSES USING COMBINED MHC CLASS II TETRAMER AND INTRACELLULAR CYTOKINE STAINING Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 435) Daniel Kaufmann1, B Wagner1, A Sette2, M Johnston1, D Strick1, B Walker1, J Zaunders3, and E Rosenberg1 The use of an optimized assay combining class II tetramer staining and intracellular staining allows assessment of HIV-specific TH cells with sensitivity comparable to ELISpot assays while allowing characterization of both cytokine- and non-cytokine-secreting TH cells. At the time points choosen for study, frequencies of Tet+ were low, with a higher fraction of IFN-γ+ cells in the presence of viremia. Early after recurrence of viremia, a high proportion of TH cells specific for some HIV epitopes can be activated and enter cell cycle. These cells may be particularly vulnerable to infection by HIV. |
| 436 | DE NOVO EXPRESSION OF CD40L (CD154) IDENTIFIES ANTIGEN-SPECIFIC CD4+ T CELLS THAT EXPRESS MULTIPLE CYTOKINES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 436) Pratip Chattopadhyay, J Yu, and M Roederer This assay improves upon previous methods, overcoming problems of transient expression. It provides a non-lethal alternative to intracellular cytokine measurements for detection of antigen-specific CD4+ T-cells; in particular it marks those cells expressing multiple cytokines. Finally, it describes a biologic aspect of antigen-specific responses: ability to provide CD154-mediated costimulatory signals. |
| 437 | ANTI-HIV ACTIVITY OF THE MHC NONRESTRICTED HUMAN CYTOTOXIC T-CELL LINE TALL-104 Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 437) J Chehimi1, Livio Azzoni1, L Shawver2, M Farabaugh1, S Creer1, E Kovacs1, and L Montaner1 We present evidence documenting the ability of TALL-104 cells to inhibit in vitro viral replication in acutely and chronically HIV-infected cells. TALL-104’s anti-HIV activity identifies a potential new non-MHC-restricted approach to inhibit HIV-1 replication. |
| 438 | HIV p24 aa14-22-MEDIATED STABILIZATION OF HLA-E RESULTS IN ENHANCED SUSCEPTIBILITY OF TARGET CELLS AGAINST LYSIS BY γ/δ T Cells Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 438) Jacob Nattermann, M von Lilienfeldt-Toal, H Nischalke, T Sauerbruch, J Rockstroh, U Spengler, and Kompetenznetz HIV/AIDS Our data show that γ/δ T cells can recognize and lyse target cells expressing the HLA-E/HIV p24 aa14-22 complex. This recognition is mediated via the T-cell receptor and may be a mechanism to counteract reduced NK cell activity induced by this peptide. |
| 439 | LIGATION OF CD28 ALONE BY ITS NATURAL LIGAND, CD86, INDUCES LIPID RAFT POLARIZATION IN HUMAN CD4 T CELLS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 439) B Kovacs1, R Parry2, E Fan1, B Freiberg3, A Thomas2, R Rutherford2, C Rumbley2, J Riley2, and T Finkel1,2 We show that lipid raft polarization in human CD4 T cells can occur in the absence of TCR triggering, driven solely by the CD28/CD86 interaction. This result has implications for mechanisms of T-cell activation. Abnormalities in this process could alter T- and B-cell tolerance and susceptibility to infection. HIV virions preferentially incorporate CD86 into their membranes and lipid rafts facilitate HIV entry. These virions have been shown to trigger NFκB activation in a CD86-dependent manner similar to that found in our studies. The heightened immune activation observed in HIV-infected individuals enhances CD86 expression, which in turn could induce lipid rafts polarization between infected cells and resting T cells, permitting formation of the virological synapse and HIV entry into non-cycling T cells. The ability of CD86 to induce lipid rafts may in part explain the susceptibility of resting T cells to HIV infection. |
| Session 81—Poster Abstracts T-Cell Epitopes and Virus Escape |
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| 440 | HLA-B63 (HLA-B*1516/B*1517) PRESENTS HLA-B57- AND HLA-B58-RESTRICTED CTL EPITOPES AND IS ASSOCIATED WITH LOW HIV VIRAL LOAD Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 440) Nicole Frahm1, S Adams2, P Kiepiela3, H Hewitt1, C Linde1, M Lichterfeld1, E Pae4, M Feeney1, T Roach5, A St John5, M Altfeld1, F Marincola2, B Walker1, P Goulder1, and C Brander1 This study identifies a novel HLA class I allele associated with reduced HIV viral load and indicates the potential importance of specific CTL epitopes in mediating superior control of HIV replication in vivo. |
| 441 | EX VIVO NEF-SPECIFIC CD8+ HLA-A11+ T CELLS PROMISCUOUSLY RECOGNIZE HLA-A3+ TARGETS PRESENTING DEGENERATE NEF EPITOPE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 441) Pokrath Hansasuta1, S Buranapraditkun1, T Dong2, P Phanuphak1, S Rowland-Jones2, and K Ruxrungtham1 ex vivo characterization of the QK10-specific HLA-A11+ T cells by tetramer staining demonstrated the cross-reactivity of T cells recognition within HLA-A3 supertype. The function of these cross-reactive T cells was, however, impaired. The information provided by this study will lead to better understanding of HIV-specific immune responses and development of an effective HIV vaccine. |
| 442 | PREDICTION OF HLA CLASS I BINDING MOTIFS FACILITATES RAPID DEFINITION OF HIV-1-SPECIFIC CYTOTOXIC T LYMPHOCYTE EPITOPES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 442) Isobella Honeyborne1,2, D Ramduth1, S Chetty1, P Rathnavalu1, E Moodley1, C Brander3, A Lesley2, K Pfafferott2, B Walker3, and P Goulder2 The HLA class I alleles prevalent in the populations most affected by the HIV epidemic, in general have not been well characterized. Identification of 18-mer peptides targeted by CD8+ T cells allowed the restriction element to be rapidly determined by statistical methods. The process of optimizing the optimal epitope is likely to be time-consuming, however, without the means to predict it with some accuracy. Confirmation of the optimal epitope and the HLA restriction may then be undertaken with minimal expenditure of time or funds for peptide synthesis. The motif predictions described here are thus useful for facilitating rapid definition of epitopes. |
| 443 | LACK OF SEQUENCE EVOLUTION WITHIN PERSISTENTLY TARGETED CD8 EPITOPES IN CHRONIC HIV-1 INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 443) Tomohiko Koibuchi1, T Allen1, M Lichterfeld1, K O'Sullivan1, A Trocha1,2, S Kalams3, R Johnson4, and B Walker1,2 These data indicate a lack of viral evolution within persistently targeted CD8 T-cell epitopes during the chronic phase of infection, and suggest that these regions of the virus are either refractory to sequence change or that persistently activated CD8 T-cell responses in chronic infection exert little functional selection pressure. |
| 444 | A NOVEL HLA-A2- AND HLA-A24-RESTRICTED SUBTYPE A/E VIF AND VPR CTL EPITOPE IDENTIFIED IN AN HIV-1-INFECTED THAI PATIENT Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 444) Supranee Buranapraditkun1, P Hansasuta1, S Rowland-Jones2, P Phanuphak1, and K Ruxrungtham1 A new HLA-A2- and HLA-A24-restricted subtype A/E Vif and Vpu epitope of 12 to 13 aa, was identified. The results support the potential role of HIV-1 regulatory proteins to be included in an AIDS vaccine development required further investigation. |
| 445 | FUNCTIONAL HETEROGENEITY OF HIV-1-SPECIFIC CD8+ T CELL CLONOTYPES IN SUBJECTS CONTROLLING VIREMIA Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 445) Dirk Meyer-Olson1, B Simons2, S Lorey2, K Brady2, M Altfeld3, B Walker3, and S Kalams2 Our findings illustrate the heterogeneity of HIV-1-specific CD8+ T cell populations directed against single HLA-class I restricted HIV-1-epitopes and suggest that the flexibility of a diverse HIV-1-epitope specific TCR repertoire may contribute to control of viremia. |
| 446 | CROSS-REACTIVE CD8 T CELLS THAT RECOGNIZE BOTH WILD TYPE AND MUTATED HIV-1 RT SEQUENCE ARE DETECTED IN HIV-INFECTED PATIENTS TREATED BY RT INHIBITORS WITH PERSISTENT LOW VIRAL LOAD Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 446) Assia Samri1,2, A G Marcelin1, D Costagliola1,3, L Cukierman1,2, R Agher1, V Calvez1, C Duvivier1, C Katlama1, and B Autran1,2 Presence of drug-resistance mutations in HIV-1-RT do not alter the immune recognition of corresponding CD8 epitopes and are frequently recognized by CD8 T cells from patients treated and harboring these mutations. Patients with low viral load frequently recognized both wild type and mutated RT sequences compared with patients with high viral load, suggesting a possible benefit of this cross-recognition in the viral immune control. |
| 447 | DE-NOVO GENERATION OF HIV-1-SPECIFIC CD8+ T-CELL RESPONSES DIRECTED AGAINST CTL ESCAPE VARIANTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 447) T Allen, X Yu, E Kalife, L Reyor, E Rosenberg, B Walker, and Marcus Altfeld These data show for the first time that de novo responses against escape variants of CD8+ T-cell epitopes can be generated in HIV-1 infection following viral escape mutations in non-anchor residues, demonstrating the ongoing ability of the immune system to adapt to viral evolution. The ability of vaccines to induce CD8+ T-cell responses directed against both the wild type and variant forms of CD8 epitopes may help prevent the emergence of CTL-escape variants. |
| 448 | ESCAPE FROM A DOMINANT CD8 GAG RESPONSE REDUCES HIV-1 FITNESS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 448) Mark A Brockman, G Tanzi, M Lahaie, I DeSouza, K O'Sullivan, E Moy, B Walker, and T Allen Our data indicate that escape from CD8 immune pressure on the region of p24-containing TW10 results in diminished HIV-1 fitness. Because the effect on replication was dependent on the target cell line used, the mechanism of this difference may relate to the fact that the H219 and T242 lie within and adjacent to the cyclophilin A (CypA)-binding domain of p24 that is critical for HIV-1 infectivity. Prior studies indicate that CEM cells express higher amounts of CypA than Jurkat cells or CD4 lymphocytes and support replication of viruses with CypA binding defects. Our results are consistent with an alteration of CypA binding in B57-TW10 escape mutants that may relate to the slower progression to AIDS in HLA-B57+ patients. |
| 449 | FREQUENCY OF INTER-CLADE CROSS-REACTIVITY OF HIV-SPECIFIC T-CELL RESPONSES DEPENDS ON SEQUENCE ENTROPY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 449) Xu G Yu1, M Lichterfeld1, B Perkins1, E Kalife1, J Chen1, E Pae2, D Cohen2, B Walker1, and M Altfeld1 In this first study analyzing the cross-reactivity of HIV-specific CD8 T-cell responses on the single-epitope level demonstrates that the frequency of inter-clade cross-reactivity of HIV-specific T cells largely depends on the entropy of the targeted epitopes. HIV vaccines therefore should include viral regions with low entropy to induce broadly cross-reactive immune responses. |
| 450 | THE DOMINANT CD4 EPITOPES IN HIV-1 B CLADE INFECTION ARE INFREQUENTLY TARGETED BY CD4+ T CELLS IN HIV-1 C CLADE INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 450) Danni Ramduth1, C Thobakgale1, A Rathod1, D Kaufmann2, M Altfeld2, M Addo2, H Coovadia1, P Kiepiela1, P Goulder3, B Walker2, and HIV Pathogenesis Programme Study Group This study indicates that although HIV-1 clade-C Gag is highly immunogenic for virus-specific CD4 T cells, regions other than those identified by the B-clade-based study are targeted by CD4+ T cells in C-clade infection. A more comprehensive screening for CD4+ restricted epitopes in a larger C-clade infected cohort, and their association with class II HLA types is currently underway. |
| 451 | HLA-RESTRICTED IMMUNE RESPONSES HAVE DRIVEN THE EVOLUTION OF HIV-1 CLADES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 451) L Park1, P Goulder2,3, P Kiepiela4, C Brander3, B Walker3,5, B Korber6, J Szinger6, J Keller1, Mina John1, D Nolan1, and S Mallal1 After introduction of an HIV variant into a host, CTL-mediated immune pressure drives viral evolution within that host. At a population level we propose that the evolution of clades similarly reflects both founder effects and the selective pressures provided by the population HLA distribution. |
| Session 82—Poster Abstracts T-Cell Subsets and the Thymus in HIV Infection |
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| 452 | INCREASED PROPORTION OF CD31+-NAÏVE T CELLS IN HIV INFECTION IS NOT DUE TO A TRUE INCREASE IN RECENT THYMIC EMIGRANTS BUT A DEPLETION OF CD31+-NAÏVE T-CELLS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 452) F Wightman1 and Sharon Lewin1,2 HIV infection is characterized by an increase in the proportion of CD31+ naïve T cells due to a relative depletion of CD31– naïve T cells. HIV cannot directly infect differentiated CD31– naïve T cells ex vivo. The mechanism of selective depletion and infection of CD31– naïve T cells in vivo remains to be elucidated. |
| 453 | CD31 EXPRESSION IDENTIFIES A SUBSET OF NAÏVE CD4 T CELLS ENRICHED IN PRIMARY THYMIC EMIGRANTS IN HIV-INFECTED PATIENTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 453) Meena Ramchandani1, V Natarajan2, J Shen1, J Mican1, C Lane1, and I Sereti1 These data suggest that naïve CD4+/CD31– T cells represent a peripherally expanded subset in HIV-infected patients. Expression of CD31 can thus be used in HIV infection to identify 2 distinct naïve CD4 T cell subsets with different replicative history and functional potential. |
| 454 | DIFFERENCES IN THYMIC FUNCTION IDENTIFY DISTINCT PATHWAYS OF T-CELL RECONSTITUTION IN ADULT HIV-1 DISEASE: AN ANALYSIS IN AN AGE-DIFFERENTIATED PROSPECTIVE COHORT (ACTG 5015) Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 454) Robert Kalayjian1,11, P Minya2, J Spritzler3, A Landay4, R Pollard5, V Stocker6, L Al-Harthi4, B Gross7, I Francis7, S Fiscus8, P Tebas9, V Valcour10, M Lederman11, and AIDS Clinical Trials 5015 Protocol Tearm These analyses support a model of T-cell regeneration in HIV-disease that follows distinct pathways according to thymic size or function, suggesting that IL-7 contributes to HAART-associated T-cell expansion in low thymic function settings, while immune activation drives cellular losses in persons with greater thymic function. |
| 455 | EXPRESSION OF CD25 (IL-2R) AND CD127 (IL-7R) ON CD4+ T CELLS DEFINES 3 CELL SUBSETS THAT ARE DIFFERENTIALLY DEPLETED DURING HIV INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 455) Richard Dunham1, H Albrecht2, A Muthukumar3, A Weintrob2, M Paiardini1, B Cervasi1, S Gordon1, M Feinberg1, D Sodora3, and G Silvestri1 Expression of CD25 and CD127 on CD4+ T cells identifies three subsets of CD4+ T cells with specific immunophenotypic and functional features. As changes in the relative proportion of these CD4+ T-cell subsets correlates with the main markers of HIV disease progression, measurement of CD25 and CD127 on CD4+ T cells may provide important information as to the qualitative loss of in vivo CD4+ T cell function induced by HIV infection. |
| 456 | PERIPHERAL S PHASE T CELLS IN HIV DISEASE ARE RELATED TO PLASMA HIV RNA LEVELS AND LACK EVIDENCE FOR RECENT T-CELL RECEPTOR ACTIVATION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 456) Scott Sieg, B Rodriguez, R Asaad, D Bazdar, and M Lederman Central memory T cells may be highly susceptible to mechanisms of immune activation in HIV disease, leading to S phase entry. Although immune activation due to viral replication and not homeostatic responses to lymphopenia appear to explain the increased frequencies of S phase lymphocytes in HIV disease, evidence that peripheral S phase T cells are responding to recent T-cell receptor stimulation is lacking, raising the possibility that these cells are largely activated by bystander mechanisms. |
| Session 83—Poster Abstracts Cellular Responses in Exposed Uninfected Individuals |
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| 457 | COMPARISON OF IMMUNE RESPONSES TO HIV GAG, POL, AND NEF IN EXPOSED UNINFECTED SUBJECTS VS TREATMENT-NAÏVE CHRONICALLY HIV-INFECTED INDIVIDUALS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 457) Kenneth Huang1, G Makedonas1, Y Peretz1, J Bruneau2, F Lamothe2, C Tsoukas1, C Lowndes3, M Alary3, and N Bernard1 Comprehensive analysis of Gag-, Pol-, and Nef-specific IFN-γ secretion revealed that EU recognized HIV Gag most frequently as do HIV-infected subjects. In comparison to EU, untreated HIV-infected progressors have broader and stronger IFN-γ T-cell responses with similar pattern of HIV recognition. Although comprehensive screening has the potential to identify new recognition specificities, EU do not appear to recognize greater percentage of novel epitopes than do chronically HIV-infected subjects. |
| 458 | DISTINCT PATTERNS OF HIV-SPECIFIC MEMORY AND NAÏVE T LYMPHOCYTES IN HIV-EXPOSED UNINFECTED INDIVIDUALS AND IN HIV-INFECTED PATIENTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 458) Monica Schenal1, S Lo Caputo2, F Fasano1, F Vichi2, M Saresella3, P Pierotti2, M Villa1, F Mazzotta2, D Trabattoni1, and M Clerici1 Exposure to HIV occurs in high-risk seronegative individuals; the observation that naïve cells and CM are skewed in ESN indicate that this exposure is robust enough to modulate the CM/EM ratio, The increase in late effectors and in NK cells seen in ESN suggests a role for these cells in preventing actual infection. |
| 459 | HIV-SPECIFIC T-CELL MEMORY AMONG HIV-EXPOSED, UNINFECTED SUBJECTS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 459) George Makedonas1, Y Peretz1, J Bruneau2, F Lamothe2, M Alary3, C Lowndes3, C Tsoukas1, and N Bernard1 HIV-specific T cells in HIV-exposed, uninfected subjects secrete IL-2 and show marked proliferation in response to HIV stimulation. These characteristics are consistent with antigen experienced Central memory T cells, and support the notion that HIV-exposed, uninfected individuals mount a cellular response to HIV that may contribute to their persistent seronegativity. |
| Session 84—Poster Abstracts CD8 Responses |
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| 460 | EVALUATING IMMUNE CORRELATES OF HIV-1 SHEDDING IN THE MALE GENITAL TRACT Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 460) Prameet Sheth1, A Danesh1, K Shahabi1, A Rebbapragada1, C Kovacs2, R Dimayuga2, K MacDonald1,3, T Mazzulli1, D Kelvin1,4, and R Kaul1,5 HIV-specific CD8+ T-cell IFN-γ responses are present at high frequencies in the semen of therapy-naïve infected men, but do not correlate with levels of viral shedding. Semen inflammatory cytokines were associated with both increased virus shedding and with virus-specific CD8+ T-cell responses, but causality cannot be determined in the context of this cross-sectional study. |
| 461 | IMPAIRED RESPONSIVENESS OF HIV-SPECIFIC CD8 T LYMPHOCYTES CAUSED BY HIGH-AFFINITY T-CELL RECEPTOR-LIGAND INTERACTIONS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 461) Takamasa Ueno1, H Tomiyama1, M Fujiwara1, S Oka2, and M Takiguchi1 Taken together, these data indicate that high-affinity TCR-ligand interactions can cause an additional level of functional defects in human CD8 T cells, providing further insights into the immune evasion mechanisms by HIV. |
| 462 | PREFERENTIAL RECRUITMENT OF HIGH-AVIDITY HIV-1-SPECIFIC CD8+ T CELLS IN ACUTE HIV-1 INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 462) Mathias Lichterfeld, X Yu, S Mui, M Johnston, E Rosenberg, B Walker, and M Altfeld In acute infection, HIV-1-specific CD8+ T cell clones with high-avidity TCR seem to be preferentially recruited, while additional CD8+ T-cell clones with lower avidity emerge during chronic infection. |
| 463 | STEREOTYPIC ESCAPE FROM CD8+ T-CELL RESPONSES REPRESENTS A MAJOR DRIVING FORCE OF HIV-1 SEQUENCE DIVERSITY AND REVEALS CONSTRAINTS ON HIV-1 EVOLUTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 463) Todd Allen1, M Altfeld1, S Geer1, E Kalife1, C Moore2, K O'Sullivan1, I DeSouza1, D Kaufmann1, M Lahaie1, L Reyor1, C Brander1, H Jessen3, E Rosenberg1, S Mallal2, and B Walker1 These data indicate a dominant role of cellular immune responses in driving both individual and global HIV-1 evolution, and the stereotypic nature of acquired mutations provides evidence for constraints on evolution of highly variable RNA viruses. |
| 464 | HEIGHTENED HIV RNA PRODUCTION IN LYMPHOID FOLLICLES COINCIDES WITH DIMINISHED NUMBERS OF HIV-SPECIFIC CD8+ CELLS AT THAT SITE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 464) Elizabeth Connick1, J Folkvord1, T Mattila2, M Givens1, R Schlichtemeier1, M Ray1, and P Skinner2 Heightened HIV replication in follicles may be due to the failure of HIV-specific cells to accumulate at that site. This could explain the persistence of HIV replication in lymphoid tissue despite intact CTL effector function. |
| 465 | SDF-1α IS A MORE POTENT INDUCER OF HIV-1-SPECIFIC CD8+ T-CELL CHEMOTAXIS THAN CX3CL1 Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 465) Amie Meditz1, K Lesh2, R Schlichtemeier1, M Givens1, J Folkvord1, L Shapiro1, and E Connick1 Soluble SDF is a more potent inducer of chemotaxis than soluble CX3CL1 for CD8+ T cells, including HIV-specific cells. Membrane-bound CX3CL1, however, modulates CD8+ T-cell chemotaxis, and may be more physiologically relevant than soluble CX3CL1. Both SDF and CX3CL1 may play a role in the localization of HIV-specific CD8+ T cells in lymphoid tissue. |
| Session 85—Poster Abstracts CD8 T-Cell Dysfunction in HIV Infection |
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| 466 | ACTIVATED HIV-SPECIFIC CD8+ T CELLS ARE CHARACTERIZED BY A PRO-APOPTOTIC MITOCHONDRIAL STATUS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 466) Constantinos Petrovas1, Y Mueller1, I Dimitriou1, J Witek1, J Altman2, and P Katsikis1 Activation of HIV-specific CD8+ T cells is associated with a pro-apoptotic mitochondrial state that potentially primes them to apoptosis. |
| 467 | PREVENTING REPLICATIVE SENESCENCE IN HIV-SPECIFIC CD8 T CELLS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 467) Rita Effros1,2, M Dagarag1, S Fauce1, R Marcsisin1, and J Man1 Targeted genetic or chemical manipulation of telomerase constitutes a potential approach for preventing the functional and phenotypic changes associated with CD8 T-cell exhaustion in HIV disease. |
| Session 86—Poster Abstracts Shifts in Cellular Responses during HIV/SIV Infection |
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| 468 | T-CELLS SPECIFIC FOR HIV GAG, NOT NEF, DOMINATE THE EARLY HIV-SPECIFIC T-CELL IMMUNE RESPONSE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 468) L Sharp1, J Chapman1, H Tomiyama2, M Brunialti2, K Bassichetto3, D Nixon1, and Esper Kallas2 Our results show that in this cohort of 53 recently infected subjects in São Paulo, Brazil, HIV-gag was preferentially recognized compared with nef, and we did not observe a dominance of early nef responses. |
| 469 | SIV-SPECIFIC CD4+ T-CELL RESPONSES DURING PRIMARY INFECTION IN RHESUS MACAQUES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 469) M C Gauduin1, Stephen Walsh2, A Barabasz1, Y Yu1, M Piatak3, J Lifson3, and R Johnson2 Primary infection with SIV results in induction of a relatively strong and broadly directed virus-specific CD4+ T-cell response. However, in animals infected with pathogenic SIV strains, levels of SIV-specific CD4+ T cells rapidly decline. Detailed analysis of the generation and loss of SIV-specific CD4+ T cells during primary infection may yield insights into determinants of control of viremia and progression to AIDS. |
| 470 | THE PROPORTION OF CYTOMEGALOVIRUS-SPECIFIC CD4+ AND CD8+ T-CELLS IS ELEVATED EARLY IN THE COURSE OF HIV INFECTION AND IS ASSOCIATED WITH IMMUNE ACTIVATION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 470) D Naeger1, S Deeks1, E Sinclair1,2, D Bangsberg1, M Roland1, F Hecht1, and Jeffrey Martin1 Increased proportions of CMV-specific CD4+ and CD8+ T-cells are seen early in HIV infection and, for at least the CD8+ T-cell response, are maintained both in chronic untreated and treated HIV disease. This suggests that before overt immunodeficiency occurs, HIV infection results in increased sub-clinical CMV replication and/or a heightened immunologic response to CMV. Regardless of mechanism, disproportionate CMV reactivity may contribute to the elevated T-cell activation observed in HIV infection and may play an etiologic role in HIV disease progression. |
| 471 | EFFECT OF VIRUS PERSISTENCE, ANTIGEN EXPOSURE, AND LEVELS ON MEMORY CD4 T-CELL RESPONSES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 471) Alexandre Harari, R Correa, F Vallelian, D Ciuffreda, and G Pantaleo Virus persistence and antigen levels dictate the functional composition of CD4 T-cell populations in different models of immune response. |
| 472 | DIFFERENCES IN HIV-SPECIFIC IFN-γ AND IL-2 RESPONSES IN HIV-INFECTED PROGRESSORS AND NON-PROGRESSORS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 472) Yoav Peretz, K Huang, G Makedonas, C Tsoukas, and N Bernard Our findings indicate that antigen-specific IL2 secretion is found only in patients with a benign course of disease. |
| 473 | HIV DISEASE PROGRESSION DESPITE INITIALLY STRONG HIV-SPECIFIC CD4+ T-CELL RESPONSES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 473) Christine Jansen1,5, I De Cuyper1,5, B Hooibrink2,5, R Coutinho3,5, D van Baarle4, and F Miedema4 Our data for the first time indicate that the early presence of HIV-specific CD4+ T-cell responses does not appear to protect against rapid progression to AIDS in treatment-naïve patients. CD4+ T-cell help was not directly related to preserved CTL function, suggesting that loss of HIV-specific CTL function in individuals progressing to AIDS cannot be exclusively explained by lack of CD4+ T-cell help. |
| 474 | ONSET OF HIV-1 VIREMIA GIVES DIVERGENT IN VITRO AND IN VIVO CORRELATES OF HIV-SPECIFIC T-CELL RESPONSES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 474) Dag Kvale1, A M Kran1, M Sommerfelt2, J Nyhus2, I Baksaas3, J Bruun1, and B Sørensen2 Onset of HIV-1 viremia induced a substantial discrepancy between preserved HIV-specific immune responses in vivo and decreased T-cell responsiveness in PBMC in vitro. These results suggest that antigen-stimulated PBMC, as the only surrogate marker for HIV-related immune responses during viremia, may not accurately reflect HIV-related immune responses in vivo. |
| 475 | INFLUENCE OF PROLIFERATIVE, IFN-γ AND IL-2-PRODUCING T-CELL RESPONSES TO HIV-2 IN UNTREATED HIV-2 INFECTION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 475) Nadia Alatrakchi1, F Damond2, S Matheron2, S Tempelhoff3, P Campa2, G Carcelain4, F Brun-Vezinet4, B Autran4, and French HIV-2 study group Proliferative, IFN-γ- and IL-2-producing T-cell responses to HIV-2 are as robust as toward CMV in subjects with undetectable HIV-2 RNA, independently of CD4 depletion. In addition, despite altered IL-2 responses, compared with IFN-γ, proliferative responses remained associated with viral control. |
| Session 87—Poster Abstracts Changes in Cellular Responses with Antiretroviral Therapy |
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| 476 | LONG-TERM HAART IN CHRONIC HIV-1 INFECTION: EVIDENCE FOR RECONSTITUTION OF ANTIVIRAL IMMUNITY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 476) C Jansen1, E Piriou1, I De Cuyper1, K van Dort1, Debbie van Baarle2, and F Miedema2 Initiation of HAART resulted in a transient increase in HIV-specific IL-2+ and IFN-γ+ CD4+ T cells, and to a lesser extend of IL-2+ CD4+ T-cells. After 50 months, HAART resulted in an increase in HIV-specific CD4+ T-cell proliferative capacity. Furthermore, responses to herpes viruses were restored, suggesting reconstitution of viral immunity as a mechanism behind the observed enhanced proliferation of HIV-specific CD4+ T cells after 5 years of HAART. |
| 477 | MAINTENANCE OF HIV-SPECIFIC IMMUNE RESPONSES IN CHRONICALLY HIV-1-INFECTED SUBJECTS WITH LOW CD4+ T-CELL NADIRS ON HAART Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 477) M Atif Siddique1, K Hartman2, E Dragileva2, D Weng Cherng3, R Wang3, M Dondero4, A Shintani1, T Gebretsadik1, L Peiperl5, F Valentine6, and S Kalams1 We conclude that while nadir CD4+ T-cell numbers help predict the magnitude of HIV-specific cell-mediated immune responses, even subjects with low CD4+ T-cell nadirs had detectable HIV-specific immune responses. Since the goal of immunotherapy will be to augment these immune responses, future studies should not exclude subjects with low CD4+ T-cell nadirs. |
| 478 | HIV-SPECIFIC CD4+ T CELLS ARE PRESERVED WHEN VIRUS REBOUNDS WHILE TURNOVER AND ACTIVATION INCREASES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 478) Thomas Scriba1, H T Zhang1, H Brown1, A Oxenius2, S Fidler3, J Fox3, J Weber3, P Klenerman1, C Day1, M Lucas1, and R Phillips1 Our data show that HIV-specific CD4+ T cells are not deleted when viremia rebounds. Their turnover increases markedly and they acquire markers consistent with effector functions. |
| 479 | IMMUNOLOGIC PRESSURE WITHIN CLASS I-RESTRICTED COGNATE HIV EPITOPES DURING HAART Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 479) Joseph Casazza, M Betts, B Hill, J Brenchley, D Price, D Douek, and R Koup These data show that CTL-mediated pressure can continue to affect viral evolution after initiation of HAART, even when treatment drives viral load below detectable levels. |
| 480 | MARKERS OF IMMUNE ACTIVATION, AGE, AND CMV LYMPHOPROLIFERATIVE RESPONSE PREDICT VIROLOGIC FAILURE IN NAÏVE HIV-INFECTED PATIENTS ON HAART: AACTG 384 STUDY AND 5007 SUBSTUDY Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 480) Benigno Rodriguez1, M Pu2, J Spritzler2, D Asmuth3, R Gandhi4, M Nokta5, G Robbins4, R Pollard3, and A5007S substudy and A384 Teams In antiretroviral-naïve HIV-infected patients initiating HAART, higher proportion of CD38/HLA-DR+ CD4 T cells, older age, and presence of a CMV LP response were associated with longer time to virologic failure. Neither thymic size nor other immune indices were found to be independently associated with time to virologic failure in this study. |
| 481 | CMV-SPECIFIC CELL-MEDIATED IMMUNITY CONFERS PROTECTION AGAINST CMV VIREMIA AND END-ORGAN DISEASE IN HIV-INFECTED PATIENTS IN THE ERA OF HAART (ACTG360) Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 481) Adriana Weinberg1, M Kendall2, C Tierney2, R Bosch2, J Patterson-Bartlett1, A Erice3, M Hirsch4, B Polsky5, and ACTG 360 team CMV-specific cell-mediated immunity measured by IFN-γ ELISpot was associated with protection against CMV viremia and CMV end-organ disease in HIV-infected patients. We were unable to demonstrate a boosting effect of CMV viremia on CMV immunity in this group of patients. |
| 482 | DECREASED IL-7 RECEPTOR-α EXPRESSION ON CD4 AND CD8 T CELLS IN HIV-INFECTED PATIENTS IS ASSOCIATED WITH INCREASED IMMUNE ACTIVATION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 482) Sarah Wynne1, J Metcalf1, J Higgins2, R Stevens2, M Nason1, H Lane1, and I Sereti1 These data suggest that dysfunction of the IL-7 system persists in HAART-treated patients. Decreased expression of IL-7Rα in T cells of HIV+ patients is associated with increased immune activation and observed despite low plasma IL-7 levels. Further decrease of IL-7Rα on CD4 T cells in patients treated with IL-2 may be a means of distributing pro-survival cytokines. |
| 483 | ENFUVIRTIDE: IN VITRO STUDIES ADDRESSING THE PUTATIVE IMMUNOTOXIC EFFECTS RELATED TO ACTIVATION OF N-FORMYL PEPTIDE RECEPTORS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 483) F Regenass1, M Adibzadeh1, Thomas Steele2, and H Kropshofer1 This study suggests that ENF is unlikely to exert an immunosuppressive effect on the key cells of the innate or adaptive immune system. |
| Session 88—Poster Abstracts Construction and Evaluation of Vaccine Strategies |
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| 484 | ELECTROPORATION SIGNIFICANTLY ENHANCES CELL-MEDIATED AND HUMORAL IMMUNE RESPONSES TO DNA-BASED HIV-1 VACCINES IN ANIMAL MODELS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 484) David Gardiner1,2, Y Huang1, S Basu1, D Hannaman3, A Luxembourg3, B Ellefsen3, Y Song1, and D Ho1 Electroporation provides consistent and significant enhancement of cell-mediated and humoral responses in 2 animal species. Antibody responses, in particular, achieve levels not possible via standard IM delivery. These results support future studies examining the enhancement of DNA vaccination provided by electroporation in humans. |
| 485 | DESIGN AND IN VITRO CHARACTERIZATION OF A DNA PRIME VIRUS-LIKE PARTICLE BOOST HIV-1 VACCINE TARGETING THE MEMBRANE-PROXIMAL REGION OF gp41 Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 485) David Gardiner1,2, Y Huang2, S Basu2, Y Song2, and D Ho2 These dual promoter systems provide a strategy for expression of modified HIV gp41 in the context of a VLP. This approach may present gp41 in a conformation capable of neutralizing antibody induction. Immunogenicity studies are ongoing. |
| 486 | ENHANCED IMMUNITY TO HIV-1 USING DNA PRIME / RECOMBINANT ENV TRIMER BOOST Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 486) Joseph F Bower1, Y Li2, R Wyatt2, and T Ross1 In conclusion, regardless of the priming dose or the form of Env, the level of neutralizing antibodies can be significantly enhanced following an Env-trimer protein boost. |
| 487 | BETTER CONSERVATION OF CD8 T- CELL RESPONSE THAN CD4 T- CELL RESPONSE ACROSS MULTIPLE CLADES OF HIV-1 RAISED BY A CLADE B DNA/MVA HIV-1 VACCINE IN MACAQUES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 487) Rama Rao Amara, S Sharma, P Nigam, and H Robinson Our results clearly demonstrate that the DNA/MVA vaccines raise broad multi-clade reactive CD8 T cells and that the cross-reactivity of the elicited response will be more limited by CD4 help than CD8 effector function. |
| 488 | GENERATION OF CROSS-REACTIVE NEUTRALIZING ANTIBODY AGAINST HIV-1 BY A DNA/MVA SHIV-89.6 VACCINE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 488) Harriet Robinson1, D Montefiori2, F Villinger1, and R Amara1 DNA/MVA SHIV-89.6 vaccines can support the avidity maturation of the anti-Env-antigen response and prime antigen capable of neutralizing primary isolates. This potential is further enhanced by GM-CSF DNA. |
| 489 | SIGNATURE FOR LONG-TERM VACCINE-MEDIATED CONTROL OF A SHIV-89.6P CHALLENGE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 489) Shanmugalakshmi Sadagopal1, R Amara1, D Montefiori2, L Wyatt3, S Staprans1, H McClure1, B Moss3, and H Robinson1 Our study reveals that a signature for successful post-challenge vaccine-mediated control of an immunodeficiency virus infection is a stable, low-breadth, low- frequency CD8 and CD4 T-cell response, capable of co-producing IFN-γ and IL-2. |
| 490 | VIRUS-SPECIFIC MUCOSAL AND SYSTEMIC IMMUNITY INDUCED BY NASAL OR INTRAMUSCULAR DNA-MVA VACCINATION AND ITS EFFECT ON SHIV CHALLENGE Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 490) Ewa Micewicz1, S W Wang1, P Kozlowski1, D Aurora1, A Carville2, K Mansfield2, and A Aldovini1 The data indicate that the intramuscular vaccination with SHIV Gag antigen may provide a better control of peak viremia than its nasal administration but that there is no significant difference in long-term protection from CD4 loss in the groups. In addition, we observed that the control of viremia paralleled the presence of SHIV-specific CD4+/IL-2 secreting cells, which are thought to be important for virus containment. Priming of these cells occurred during vaccination but we cannot establish whether their persistence after infection is the cause or the consequence of the viremia control. |
| 491 | FUNCTIONALLY SIGNIFICANT ADENOVIRUS SEROTYPE 5 NEUTRALIZING ANTIBODIES ARE DIRECTED PRIMARILY AGAINST THE ADENOVIRUS HEXON PROTEIN Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 491) Shawn Sumida1, D Truitt1, A Lemckert2, R Vogels2, J Custers2, M Addo3, S Lockman4, T Peter4, F Peyerl1, S Jackson1, M Essex4, B Walker3, J Goudsmit2, M Havenga2, and D Barouch1 These data demonstrate that functionally significant ADV5-specific Nab are directed primarily against the ADV5 hexon protein. Moreover, these studies suggest a potential strategy for engineering novel ADV5 vectors to evade dominant ADV5-specific Nab. |
| 492 | A NOVEL CLOSTRIDIUM PERFRINGENS-BASED SIV VACCINE INDUCES MATURATION OF DENDRITIC CELLS AND ENABLES DENDRITIC CELL PRIMING OF T CELLS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 492) Ruth Helmus, Y Chen, T Wehrli, and P Gupta These data demonstrate that SIV p27 delivered via our recombinant C. perfringens can be taken up and processed by immature DC. Maturation of DC is stimulated in response to the vaccine. In addition, mature DC stimulate IFN-γ-producing and cytolytically active p27-specific T cells. These results show that DC can mediate the formation of an immune response against SIV p27 when exposed to the C. perfringens vaccine in vitro and suggest that DC will mediate strong responses in vivo following oral immunization. |
| Session 89—Poster Abstracts Enhancing Immune Responses to Vaccines |
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| 493 | PLASMID VACCINES CONTAINING ENGINEERED IL-12 OR IL-15 DRIVE HIGH LEVELS OF CD8 ANTIGEN-SPECIFIC EFFECTOR CELLS WITH DIFFERENT IMMUNOLOGICAL PROFILES Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 493) J Boyer1, Sandra Calarota1, M Kutzler1, E Nietrzeba1, S Kumar1, R Parkinson1, V Roopchand2, M Sidhu2, M Lewis3, P Silvera4, G Pavalkis5, K Muthumani1, T Waldman5, and D Weiner1 This study illustrates that molecular adjuvants allow multiple immunizations and boosting cycles; co-stimulation as a molecular adjuvant strategy will need more attention; IL12 and IL15 both enhance a plasmid antigen-induced CD8 immune response; and, finally, different cellular profiles can be elicited by each adjuvant. We have illustrated for the first time vaccine-specific control over the direction of an induced immune response using a plasmid vaccine by inducing separate induction of granzyme B induction versus IFNγ. This study suggests that custom tailoring of a vaccine response in vivo is possible with DNA-based vaccines. |
| 494 | HLA-DRIVEN OPTIMIZATION OF AN HIV VACCINE IMMUNOGEN Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 494) Vladimir Jojic1, D Heckerman1, C Kadie1, C Meek1, C Moore2, M John2, and S Mallal2 These data demonstrate a novel, rational approach to optimizing the immunogenicity of an HIV vaccine against diverse circulating viruses in a human population, guided by knowledge of the population HLA. |
| 495 | ENHANCING RESPONSES TO DNA VACCINATION USING PLASMIDS FOR SOLUBLE, MULTIMERIC CD40 LIGAND AND GLUCOCORTICOID-INDUCED TUMOR NECROSIS FACTOR RECEPTOR LIGAND Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 495) G Stone1, S Barzee1, V Snarsky1, K Kee1, X F Yu2, and Richard Kornbluth1 These results indicate that fusions between immunostimulatory TNF superfamilies and collectins can significantly enhance responses to HIV DNA vaccines and act as a novel vaccine adjuvant. |
| 496 | NOVEL BACTERIA-DERIVED GLYCOLIPIDS AND SULFATIDE ANALOGS ARE POTENTIAL HIV VACCINE ADJUVANTS THAT ACT THROUGH STIMULATION OF CD1d-RESTRICTED NATURAL KILLER T CELLS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 496) M Poles1,2, A Horowitz1, D Wu3, G W Xing3, Y Kinjo4, B Sullivan4, O Plettenburg3, M Kronenberg4, C H Wong3, D Ho1, and Moriya Tsuji1,2 Thus, murine and human NKT cells react to these glycolipids in a fashion comparable to α-GalCer. Since α-GalCer has been shown to enhance the efficacy of HIV vaccines in a murine model, it is likely that these novel glycolipids may also have adjuvant activity and will improve the immunogenicity of existing HIV vaccines. |
| Session 90—Poster Abstracts HIV-1 Neutralizing Antibodies |
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| 497a | ANTIGENIC AND IMMUNOGENIC ANALYSIS OF HEPATITIS B SURFACE ANTIFGEN PARTICLES CONTAINING HIV gp41-MEMBRANE PROXIMAL REGION Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 497a) Sanjay Phogat1, A Spadaccini2, I Berkower2, and R Wyatt1 In addition to using this novel platform to detect gp41-directed binding antibodies, we are also evaluating the HBsAg-MPR particles as immunogens to elicit neutralizing antibodies specific for the HIV gp41 MPR. |
| 497b | USE OF DIRECTED MOLECULAR EVOLUTION TO CREATE NOVEL HIV-1 ENVELOPE VARIANTS CAPABLE OF INDUCING BROADLY NEUTRALIZING ANTIBODY RESPONSES IN RABBITS Conf Retroviruses Opportunistic Infect 2005 Feb 22-25;12: (abstract no. 497b) X Du1, L Xu1, W Zhang1, S Tang1, J Harms2, R Robson2, M Chambers2, T Wrin3, C Petropoulos3, M Zwick4, D Burton4, and Robert Whalen1 Directed molecular evolution can be used to improve the immunogenicity of the gp120 form of HIV-1 Env. Additional rounds of directed molecular evolution provide a reiterative and logical way to enhance these incremental improvements. |
| 498 | |