2nd International AIDS Society Conference on HIV Pathogenesis and Treatment


Paris, France - July 13-16, 2003


| July 2003 | Sunday 13th . 18:00-19:30
Session 1OS - Opening Session
Opening Session
Chair persons
Michel Kazatchkine, ANRS, Paris, France
Joep Lange, University of Amsterdam, Amsterdam, The Netherlands

1* KEYNOTE LECTURE: EXPANDING ACCESS TO ANTIRETROVIRAL TREATMENT IN THE DEVELOPING WORLD: THE ECONOMIC RATIONALE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 1)
Jean-Paul Moatti, University of the Mediterranean, Marseille, France
Abstract not available
2* COMMUNITY ADDRESS: WHERE IS THE WAR CHEST AGAINST AIDS?
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 2)
Marie-Josée Mbuzenakamwe, Association Nationale de Soutien aux Séropositifs et Sidéens (ANSS), Bujumbura, Burundi
Abstract not available
| July 2003 | Monday 14th . 8:30-9:30
Session 2PL - Plenary
Chair persons
Françoise Barré-Sinoussi, Institut Pasteur, Paris, France
Souleymane Mboup, University Cheikh Anta Diop, Dakar, Senegal

3* CHALLENGES AND LESSONS LEARNED IN IMPLEMENTING ANTIRETROVIRAL THERAPY IN THE DEVELOPING WORLD
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 3)
Ernest Darkoh, Ministry of Health, Gaborone, Botswana
Abstract not available
4* HOST/VIRUS MECHANISMS IN THE MOLECULAR PATHOGENESIS OF HIV
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 4)
Nathaniel R. Landau The Salk Institute for Biological Studies, San Diego, USA
Abstract not available
| July 2003 | Monday 14th . 10:00-12:00
Session 3FO - Forum
HIV Drug Resistance
Conveners
François Clavel, Hospital Bichat-Claude Bernard, Paris, France
Daniel Kuritzkes, Partners AIDS Research Center, Harvard Medical School, Charlestown, USA

5* STATE-OF-THE ART TALK: MECHANISMS OF HIV DRUG RESISTANCE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 5)
François Clavel, Hospital Bichat-Claude Bernard, Paris, France
Abstract not available
6* STATE-OF-THE-ART TALK: USE AND CLINICAL IMPACTS OF DRUG RESISTANCE TESTING IN HIV INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 6)
Daniel Kuritzkes, Partners AIDS Research Center, Harvard Medical School, Charlestown, USA
Abstract not available
7 COMBINING TENOFOVIR TO OTHER NRTIs: IMPACT ON RESISTANCE AND VIRAL FITNESS AT THE MOLECULAR LEVEL
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 7)
B Canard1, J Deval1, KL White2, MD Miller2, J Courcambeck3, B Selmi1 and J Boretto1
Our data describe at the molecular level both how a resistant virus is unable to resist to two drugs simultaneously, and for the first time, how viral fitness of a resistant virus is directly linked to its decreased ability to use natural nucleotide substrates. All together, these data predict a benefit for the combination of tenofovir DF with 3TC, as well as open new avenues in how to drive resistant virus to reduced viral fitness.
8 POLYMORPHISM OF HIV-2 PROTEASE GENE AND SELECTION OF DRUG RESISTANCE MUTATIONS IN HIV-2 INFECTED PATIENTS INCLUDED IN THE FRENCH ANRS COHORT AND TREATED WITH PROTEASE INHIBITORS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 8)
D Descamps1, S Matheron1, F Damond1, G Peytavin1, P Campa1, S Pueyo2, F Mammano1, S Lastere1, I Farfara1, F Simon3, G Chene2 and F Brun-Vezinet1 for the French HIV-2 ANRS cohort
Mutations associated with HIV-1 PI resistance were detected in HIV-2 treated pts. Substitutions of amino acids of currently unknown impact need to be evaluated by in vitro experiments.
9 THE INHIBITORY QUOTIENT (IQ) OF TIPRANAVIR/RITONAVIR (TPV/r) in TRIPLE CLASS EXPERIENCED HIV + PATIENTS; RESULTS FROM BI 1182.52.
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 9)
DL Mayers1, VM Kohlbrenner1, C Dohnanyi1, JP Sabo1, TR MacGregor1, W Verbiest2, P McKenna2, S McCallister1
The IQ of TPV observed in this trial of HTE triple class experienced pts compares favorably IQ data for other PIs obtained from treatment-naïve pts. This high IQ, coupled with the need for multiple protease gene mutations in most HIV isolates that show decreased susceptibility to TPV, suggests that TPV/r may provide antiviral activity in the majority of HTE HIV + patients.
10 A RANDOMIZED CONTROLLED TRIAL OF PHENOTYPIC RESISTANCE TESTING IN ADDITION TO GENOTYPIC RESISTANCE TESTING: THE ERA TRIAL
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 10)
C Loveday1, DT Dunn2, H Green2, A Rinehart3 and P McKenna4 on behalf of the ERA Steering Committee
The ERA trial found no clear evidence of added value (in terms of virological response) of phenotypic resistance testing against a background of genotypic resistance testing in patients with limited therapeutic options.
| July 2003 | Monday 14th . 10:00-12:00
Session 4FO - Forum
Immunopathogenesis and Immune Restoration
Conveners
Brigitte Autran, University Hospital Pitié-Salpêtrière, Paris, France
Bruce D. Walker, Partners AIDS Research Center, Harvard Medical School, Charlestown, USA

11* STATE-OF-THE ART TALK: RATIONALE FOR HIV-SPECIFIC IMMUNOTHERAPY: LESSONS FROM CHRONIC HIV INFECTION AND IMMUNE RESTORATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 11)
Brigitte Autran, University Hospital Pitié-Salpêtrière, Paris, France
Abstract not available
12* STATE-OF-THE-ART TALK: PROSPECTS FOR IMMUNOTHERAPY OF HIV INFECTION: LESSONS FROM ACUTE INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 12)
Bruce D. Walker, Partners AIDS Research Center, Harvard Medical School, Charlestown, USA
Abstract not available
13 PRELIMINARY RESULTS OF ESPRIT (EVALUATION OF SUBCUTANEOUS PROLEUKIN IN A RANDOMISED INTERNATIONAL TRIAL): BASELINE PREDICTORS OF CD4 T-CELL RESPONSE TO INTERLEUKIN-2
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 13)
L Weiss1, J Aboulhab2, GA Babiker2, JD Bebchuk3, J Darbyshire2, D Newberry2, C Capitant1 and JP Aboulker1 for the ESPRIT research group
CD4 cell count response after the first 3 cycles of IL-2 at Month 8 is associated with a higher nadir and baseline CD4 and younger age.
14 INTERLEUKIN-7 STIMULATES T-CELL RENEWAL WITHOUT INCREASING VIRAL REPLICATION IN SIV-INFECTED MACAQUES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 14)
MT Nugeyre1, V Monceaux2, S Beq1, MC Cumont2, R Ho Tsong Fang2, L Chêne1, M Morre3, F Barré-Sinoussi1, B Hurtrel2, N Israël1
We show here that IL-7 induces both a central renewal and a peripheral expansion of T lymphocytes associated with cell activation. No increase in the viral load was shown in blood or lymph nodes. Furthermore no alarming side effect was observed. These data strengthen the rationale for the use of IL-7 as an efficient immunotherapy in AIDS.
15 IMMUNOLOGICAL IMPROVEMENT FOLLOWING HAART COINCIDES WITH RESTORED THYMIC FUNCTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 15)
R Cheynier1, R Bordi2, ML Dion2, R Woods3, J Montaner3, F Harris4, M Lederman5 and RP Sékaly2
The positive correlation between CD4 counts and intrathymic proliferation in HAART treated patients suggests the important role of thymic function in immune reconstitution following HAART.
16 THYMIC VOLUME IS INDEPENDENTLY ASSOCIATED WITH THE MAGNITUDE OF CD4+ T-CELL RECOVERY AFTER SHORT AND LONG TERM ON HAART
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 16)
E Ruiz-Mateos1, A Vallejo1, A Rubio1, N Soriano1, R de la Rosa2, S Molina1, A Sánchez-Quijano2, E Lissen2 and M Leal2 for the Viral Hepatitis and AIDS study Group
In conclusion, thymic volume is the main and only factor independently associated with the magnitude of CD4+ T-cell recovery either after short or long term on HAART. Thymic volume is not associated with the magnitude of TREC-bearing cells recovery, suggesting that other alternative mechanisms for TREC production such as redistribution and/or extrathymic synthesis might be involved.
| July 2003 | Monday 14th . 10:00-12:00
Session 5FO - Forum
Opportunistic Infections in
Resource-limited Settings

Conveners
Kevin De Cock, CDC, Nairobi, Kenya
Peter Mugyenyi, Joint Clinical Research Centre, Kampala, Uganda

17* STATE-OF-THE ART TALK: PATTERN OF OPPORTUNISTIC INFECTIONS IN AIDS PATIENTS IN AFRICA: THE UGANDAN EXPERIENCE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 17)
Peter Mugyenyi, Joint Clinical Research Centre, Kampala, Uganda
Abstract not available
18* STATE-OF-THE-ART TALK: TUBERCULOSIS IN THE CONTEXT OF HIV/AIDS IN 2003
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 18)
Kevin De Cock, CDC, Nairobi, Kenya
Abstract not available
19 BCG-INDUCED DISEASE IN HIV-INFECTED CHILDREN
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 19)
AC Hesseling1, HS Schaaf1, N Beyers1, MF Cotton1, RP Gie1, BJ Marais1, P van Helden2, WA Hanekom3 and R Warren1,3
The clinical picture was similar to tuberculosis, although right axillary adenitis is more common. Young symptomatic HIV-infected infants are at risk for BCG-related complications. Clinical features do not adequately distinguish between BCG and M. tuberculosis. Coinfection with M. tuberculosis can occur. Due to study limitations, we are unable to recommend a change in current vaccination policy. Population-based controlled studies are necessary to assess the risk of BCG in HIV-infected children.
20 PASSIVE VERSUS ACTIVE TUBERCULOSIS CASE FINDING AND ISONIAZID PREVENTIVE THERAPY AMONG HOUSEHOLD CONTACTS IN A RURAL DISTRICT OF MALAWI
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 20)
R Zachariah1, MP Spielmann1, AD Harries2, P Gomani3, SM Graham4-5, E Bakali3 and P Humblet6
Where the majority of TB patients are HIV positive, active case finding among household contacts yields 9 times more TB cases and is an opportunity for reducing TB morbidity and mortality. The need for a CXR is an obstacle for the uptake of INH prophylaxis.
21 DETECTION OF HIV, CHLAMYDIA, GONORRHEA, AND HERPES SIMPLEX BY DNA PCR IN CERVICOVAGINAL FLUIDS: CORRELATES OF MALE TO FEMALE AND FEMALE TO MALE TRANSMISSION OF HIV-1 INFECTION IN ZAMBIA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 21)
R Chavuma1 for the the Rwanda/Zambia HIV Research Group2,5
HIV is detectable in most CVF samples from HIV+ and some seroconverting women. Most HIV transmissions occurred without chlamydia, gonorrhoea, or HSV. Male-to-female transmission was associated with chlamydia and gonorrhoea, but female-to-male transmission was not. HSV shedding in CVF was associated with both acquiring and transmitting HIV.
22 INCREASING IN VITRO RESISTANCE TO FLUCONAZOLE IN CRYPTOCOCCUS NEOFORMANS ISOLATED IN CAMBODIA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 22)
B Sar1, D Monchy1, N Prak2, C Keo1 and JL Sarthou1
By contrast, FLC showed a big MIC change over time. In addition for 402 isolates the serotypes of C. neoformans were determined. 98.5% of isolate were serotype A and 1.5% were serotype B. Correlation between in vitro resistance to antifungal agents and clinical efficacy of treatment are not significantly established. Our study indicates that the resistance in vitro of C. neoformans to FLC appears to be linked to extended maintenance treatments under strictly controlled clinical prescription. C. neoformans var. neoformans is the isolate predominance of opportunistic infection in Cambodia.
| July 2003 | Monday 14th . 10:00-12:00
Session 6FO - Forum
Molecular Epidemiology of HIV and
Implications of Viral Diversity

Conveners
Francine McCutchan, US Military HIV Research Program, Rockville, USA
Martine Peeters, Institut de Recherche pour le Développement (IRD), Montpellier, France

23* STATE-OF-THE-ART TALK: OVERVIEW OF GLOBAL HIV-1 DIVERSITY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 23)
Francine McCutchan, US Military HIV Research Program, Rockville, USA
Abstract not available
24* STATE-OF-THE-ART TALK: GENETIC DIVERSITY OF HIV IN AFRICA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 24)
Martine Peeters, Institut de Recherche pour le Développement (IRD), Montpellier, France
Abstract not available
25 VIRAL LOAD (VL) AND CD4 RESPONSE TO PI CONTAINING REGIMEN IN B VERSUS NON-B TREATMENT-NAÏVE HIV-1 PATIENTS (P)
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 25)
S De Wit1, R Boulmé2, B Poll1, JC Schmit2 and N Clumeck1
The HIV population starting therapy in Belgium shows a high heterogeneity of sub-types. No difference in VL response at m24 to a PI-containing regimen was found between B and non-B sub-types whereas CD4 response was lower in the non-B p., particularly those with A sub-type. Whether this is due to viral or immune factors warrants further investigation.
26 HIV-1 ENVELOPE GENE EVOLUTION IS DRIVEN BY STRONG NEUTRALIZING ANTIBODY SELECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 26)
EE Paxinos1, T Wrin1, J Galovich1, J Beauchaine1, S Little2, DD Richman2 and CJ Petropoulos1
These findings support our hypothesis that rapid evolution of the HIV env gene following primary infection occurs in response to strong NA selective pressure and that env sequence divergence over time reflects the continual emergence of NA resistant escape variants.
27 LONG TERMINAL REPEAT SEQUENCE ANALYSIS OF THE HIV-1C EPIDEMIC IN ETHIOPIA DEMONSTRATING ASYMMETRIC PREVALENCE OF THE TWO CO-CIRCULATING GENOTYPES C AND C’: INDICATION FOR BIOLOGICAL ADVANTAGE OF THE C GENOTYPE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 27)
G Pollakis, T van Opijnen, A Kliphuis, A Abebe, J Goudsmit and MP de Baar
The surveillance of the HIV-1 circulating strains, especially in areas of high prevalence such as Ethiopia is crucial for future vaccine studies. We have identified that in Ethiopia two strains of subtype C (C and C') are co-circulating and demonstrated that recombinant progeny exist, possibly through unidirectional recombination and evolutionary pressure on the respective biological functions of the LTR promoter and the envelope protein. There is indication that one group may have a biological advantage over the other.
| July 2003 | Monday 14th . 12:30-13:30
Session 7FO - Forum
Treatment Issues in Pediatric HIV Infection
Conveners
Stéphane Blanche,, Hospital Necker-Enfants Malades, Paris, France
Katherine Luzuriaga, University of Massachussetts Medical School, Worcester, USA

28* STATE-OF-THE ART TALK: EARLY COMBINATION THERAPY: DETERMINANTS OF VIRAL SUPPRESSION AND LONG-TERM FOLLOW-UP
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 28)
Katherine Luzuriaga, University of Massachussetts Medical School, Worcester, USA
Abstract not available
29* STATE-OF-THE-ART TALK: MANAGEMENT OF PEDIATRIC ANTIRETROVIRAL TREATMENT
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 29)
Stéphane Blanche, Hospital Necker-Enfants Malades, Paris, France
Abstract not available
30 PATTERN AND CORRELATES OF VIRAL LOAD IN KENYAN HIV-1 INFECTED CHILDREN
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 30)
E Obimbo1, D Mbori-Ngacha1, P Otieno2, A Isavwa1, D Wamalwa1, C Farquhar3, R Bosire1, B Lohman1,3, B Richardson3 and G John-Stewart1,3
High peak VL is associated with high maternal VL, premature birth, high VL set point and with rapid disease progression among Kenyan HIV-1 infected infants.
31 HIGHLY ACTIVE ANTIRETROVIRAL THERAPIES AMONG HIV-1-INFECTED CHILDREN IN ABIDJAN, CÔTE D'IVOIRE (ANRS 1244)
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 31)
P Msellati5, P Fassinou1, N Elenga2, F Rouet3, R Laguide2, KA Kouakoussui2, M Timite1 and S Blanche4
Globally adherence to treatment was good. 72 children were tested for HIV-1 RNA VL and CD4 before HAART initiation (median 52 days): median VL 5.41 log, median number of CD4 182/mm3, median percentage 7.9%. After 335 days with HAART, 48% under 2.4 log and 10.7% are between 2.4 and 3.0 log cp/ml, median VL 2.53 log cp/ml, median number of CD4 479 and median percentage 18.4. HAART treatment of children in Africa is feasible and as effective as in developed countries.
32 PREDICTORS OF IMMUNOLOGIC LONG-TERM NON-PROGRESSION IN HIV-INFECTED CHILDREN IN A PROSPECTIVE BIRTH COHORT
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 32)
K McIntosh1, C Mao1, M Paul2, M Charurat3 and W Shearer2 for the Women and Infants Transmission Study (WITS)
The levels of L phenotypic markers, particularly activation markers, in the first 4 months of life may predict rapid progression in infants and allow identification of slow immunologic progressors who may not need immediate ART.
33 MORTALITY AND MORBIDITY IN HIV-INFECTED INFANTS TREATED BEFORE 6 MONTHS OF AGE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 33)
A Faye
Children given early multitherapy do not suffer the early-onset, severe form of childhood HIV infection.
| July 2003 | Monday 14th . 12:30-13:30
Session 8PL - Plenary
Extraordinary Plenary Session
20 Years of HIV Science

Chair persons
Robert C. Gallo, Institute of Human Virology, University of Maryland, Baltimore, USA
Luc Montagnier, Fondation Mondiale Recherche et Prévention Sida, Paris, France

34* KEYNOTE LECTURE: 20 YEARS OF HIV SCIENCE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 34)
Anthony S. Fauci, Director, NIAID, National Institutes of Health, Bethesda, USA
Abstract not available
35* KEYNOTE ADDRESS: FROM SCIENCE TO ACTION: CHALLENGES IN MANAGING AIDS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 35)
Nelson Mandela, Former President of the Republic of South Africa, Founder, Nelson Mandela Foundation
Abstract not available
| July 2003 | Monday 14th . 14:30-16:30
Session 9OA - Oral Abstracts
Antiretroviral Therapy
Chair persons
Mauro Schechter, Federal University of Rio de Janeiro, Brazil
Stefano Vella, Istituto Superiore della Sanità, Rome, Italy

36 BIKS STUDY (LOPINAVIR/RITONAVIR-EFAVIRENZ COMBINATION): COMPLETE 24-WEEK RESULTS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 36)
V. Ferré1, C. Allavena1, I. Poizot-Martin2, G. Beck-Wirth3, I. Cohen Codar5, P. Perré4, F. Raffi1, and the BIKS study group
The dual combination of LPV/r-EFV shows a similar immuno-virological efficacy to a NRTI-based HAART regimen with an acceptable tolerability. Durability of antiviral effect will be assessed at W48 of follow-up.
37 EMTRICITABINE, DIDANOSINE AND EFAVIRENZ ONCE-DAILY(OD) VERSUS CONTINUED PI-BASED HAART (C) IN HIV-INFECTED ADULTS WITH UNDETECTABLE PLASMA HIV-RNA: 48-WEEK RESULTS OF A PROSPECTIVE RANDOMIZED MULTICENTER TRIAL (ALIZE-ANRS99)
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 37)
J. Molina1, F. Ferchal1, V. Journot2, P Yéni3, W. Rozenbaum3, C. Rancinan2, L. Morand-Joubert3, S. Fournier1, P. Morlat2, B. Dupont3, J. Delfraissy3, P. Dellamonica4, I. Poizot-Martin5, E. Rosenthal4, G. Chêne2, and the Alize study group
The substitution of a PI-based regiment by a simple once-daily combination of emtricitabine, didanozine and efavirenz mainted full control of plasma HIV-RNA levels for 48 weeks and was well tolerated.
38 A RANDOMIZED, DOUBLE-BLIND, MULTICENTER COMPARISON OF EMTRICITABINE QD TO STAVUDINE BID IN TREATMENT-NAÏVE HIV-INFECTED PATIENTS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 38)
F. Raffi1, M. Saag2, P. Cahn3, M. Wolff4, D. Pearce5, J. Molina6, J. Hinkle7, A. Shaw7, E. Mondou7, J. Quinn7 and F. Rousseau7 for the FTC301 Study Team
Once-daily FTC demonstrated durable and superior virologic efficacy and tolerability through 60 weeks of follow-up compared to twice-daily d4T when used with once-daily ddI and EFV.
39 COMPARISON OF PI-BOOSTED INDINAVIR WITH EFAVIRENZ PLUS STAVUDINE REGIMENS IN EASIER (EUROPEAN AND SOUTH AMERICAN STUDY OF INDINAVIR, EFAVIRENZ, AND RITONAVIR)
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 39)
M Stek Jr1, B Hirschel2, J Benetucci3, G Reboredo4, D Duiculescu5, J Begovac6, K Brinkman7, D Banhegyi8, M Shivaprakash1 and J Menten1 for the EASIER study team
At 48 weeks, the compact, IDV/RTV+EFV nucleosidesparing regimen yielded similar promising efficacy and safety data as compared with results achieved using the PI+NNRTI foundation plus D4T.
40 DIRECTLY OBSERVED THERAPY (DOT) FOR HIV+ DRUG USERS (IDUs)
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 40)
FL Altice, J Mezger, J Hodges, D Bruce, S Springer and GH Friedland
Active IDUs with HIV have significant social and medical co-morbidity and disenfranchisement from the health care system. Despite these obstacles, they have improved health outcomes while on DOT. HIV+ IDUs with baseline viral suppression do not need DOT and such resource-consuming efforts should be reserved for those who might benefit most.
41 ACTG 5095: A COMPARATIVE STUDY OF 3 PROTEASE INHIBITOR-SPARING ANTIRETROVIRAL REGIMENS FOR THE INITIAL TREATMENT OF HIV INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 41)
RM Gulick1, HJ Ribaudo2, CM Shikuma3, S Lustgarten2, WA Meyer4, K Klingman5, KE Squires6, S Snyder7 and DR Kuritzkes8
In treatment-naïve pts, ZDV/3TC/ABC was inferior to EFV-containing treatment in terms of rates and time to virologic failure.
42 INDUCTION OF ANTIRETROVIRAL-NAÏVE HIV-INFECTED SUBJECTS WITH TRIZIVIR (TZV) AND SUSTIVA (EFV) FOR 48 WEEKS (ESS40013)
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 42)
M Markowitz1, J Lang2, E DeJesus3, C Hill-Zabala4, ER Lanier4, Q Liao4, K Pappa4 and M Shaefer4
TZV+EFV is a compact potent 4-drug regimen that can effectively reduce vRNA in patients with broad ranges of vRNA and CD4 cell counts. Full data from M will be presented in the future.
43 EARLY VIROLOGIC FAILURE IN A PILOT STUDY EVALUATING THE EFFICACY OF ABACAVIR, LAMIVUDINE AND TENOFOVIR IN THE TREATMENT NAÏVE HIV-INFECTED PATIENTS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 43)
C Farthing, H Khanlou and V Yeh
Although preliminary, these results raise the concern about potency and efficacy of this regimen administered once-daily in HIV treatment naïve pts, particularly those with initial VL >100,000.
| July 2003 | Monday 14th . 14:30-16:30
Session 10SY - Special Symposium
Symposium on Cellular Immunity
Chair persons
Patrice Debré, University Hospital Pitié-Salpêtrière, Paris, France
Joseph M. McCune, Gladstone Institute of Virology and Immunology, San Francisco, USA

44* SKEWED REPRESENTATION OF FUNCTIONALLY DISTINCT POPULATIONS OF VIRUS-SPECIFIC CD4 T-CELLS IN HIV-1-INFECTED SUBJETS WITH PROGRESSIVE DISEASE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 44)
Alexandre Harari, Lausanne University Hospital, Switzerland
Abstract not available
45* IMPACT OF HIV-1 SPECIFIC T-CELL RESPONSES ON VIRAL SEQUENCE VARIATIONS AND CONTROL OF VIRAL REPLICATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 45)
Marcus Altfeld, Partners AIDS Research Center, Massachusetts General Hospital, Charlestown, USA
Abstract not available
46* FAILING IMMUNE CONTROL IN HIV INFECTION: LESSONS FROM THE NATURAL COURSE OF INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 46)
Debbie van Baarle, Clinical Viro-Immunology, Sanquin Research at CLB, Amsterdam, The Netherlands
Abstract not available
47* GENERATION OF DYSFUNCTIONAL CD8 LOW SINGLE POSITIVE 8 THYMOCYTES IN THE HIV-INFECTED THYMUS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 47)
David Favre, Gladstone Institute of Virology and Immunology, The J. David Gladstone Institutes, University of California, San Francisco, USA
Abstract not available
48* CD8+ T-CELL DIFFERENTIATION TOWARDS SENESCENCE FOLLOWING ABERRANT CD8+ ACTIVATION IN HIV-1 INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 48)
Victor Appay, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK
Abstract not available
49* THE POTENTIAL OF VACCINE-ELICITED CELLULAR IMMUNE RESPONSES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 49)
Emilio A. Emini, Merck Research Laboratories, West Point, USA
Abstract not available
| July 2003 | Monday 14th . 14:30-16:30
Session 11OA - Oral Abstract
Complications of Antiretroviral Therapy
Chair persons
Andrew Carr, St.Vincent’s Hospital Sydney, Australia
Jose Gatell, University of Barcelona, Spain

50 A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF ROSIGLITAZONE FOR PATIENTS WITH HIV LIPODYSTROPHY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 50)
C Hadigan1, S Yawetz2, A Thomas3, F Havers1, PE Sax2 and S Grinspoon1
With open label extension, insulin sensitivity remained improved and SAT increased further for a net change of ±15% from baseline after 6 months. These data demonstrate positive effects of rosiglitazone on insulin sensitivity and fat in HIV-infected patients with lipodystrophy and insulin resistance. Thiazolidinediones may provide an important therapeutic benefit. Studies are needed to identify optimal dose, duration of treatment, subpopulations most likely to benefit and choice of specific thiazolidinedione to minimize effects on cholesterol.
51 BASELINE (BL) LACTATE LEVELS AND CT SCAN VALUES PREDICT THE REGRESSION OF LIPOATROPHY (LA) IN CT SCAN 48 WEEKS AFTER A SWITCH FROM STAVUDINE (D4T) TO ABACAVIR (ABC) OR ZIDOVUDINE (ZDV)
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 51)
J Hernandez1, D Ward2, V Williams1, G McComsey3, T File4, T Lonergan5, S Hessenthaler1 and R Fisher1
Subjects with LA showed progressive gains in body fat through wk 48 when d4T was replaced with either ABC or ZDV. BL lactate levels and BL CT scan values were predictive of a decrease in VAT at 48 weeks.
52 RISKS OF CARDIOVASCULAR DISEASE ASSOCIATED WITH HIGHLY ACTIVE ANTIRETROVIRAL THERAPY AMONG PERSONS TREATED FOR HIV/AIDS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 52)
AR Levy1, B Sobolev1, RS Hogg1,2, U Iloeje3, J Mukherjee3, B Yip2, M Harris2, MV O’Shaughnessy2 and JS Montaner2
This population-based analysis showed that the risk of cardiovascular disease may be increased when HIV-infected subjects were using PIs. The true association is likely to be stronger than shown here because misclassification of exposure likely reduced in magnitude of the association.
53 SHORT-TERM TOLERANCE OF EFAVIRENZ IN HIV-INFECTED AFRICAN ADULTS PARTICIPATING IN THE TRIVACAN ANRS 1269 TRIAL, ABIDJAN, CÔTE D’IVOIRE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 53)
C Danel1, R Moh1, E Messou1, A Minga1, C Seyler1, D Sauvageot1, X Anglaret3, E Bissagnene2 and R Salamon3 for the ANRS 1269 Study Group
In these preliminary data from adult patients receiving efavirenz in trial conditions (counselling on compliance), subjective symptoms were frequently self-reported, but no severe adverse event was notified and no treatment modification decided. Data available on June 2003 (350 patients) will be presented at the conference.
54 ACTG 5097s: IMPACT OF EFAVIRENZ (EFV) ON NEUROPSYCHOLOGICAL PERFORMANCE, MOOD, AND SLEEP BEHAVIOUR IN HIV-POSITIVE INDIVIDUALS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 54)
DB Clifford1, S Evans2, Y Yang2, E Acosta3, K Goodkin4 and RM Gulick5
In a large active-controlled trial, early neurologic symptoms distinct from depression or anxiety were associated with EFV use, and resolved by week 4. Improvement in neuropsychologic performance was comparable in EFV and non-EFVtreated subjects.
55 INCREASES IN CREATININE DURING THERAPY WITH TENOFOVIR DF
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 55)
M Harris1, B Yip1, N Zalunardo2, R Werb2, M Valyi1, R Hogg1 and J Montaner1
In summary, clinically significant Cr increases were observed in 7% of patients taking TDF for 6 months, resulting in at least 1% of patients discontinuing TDF during the first year. Among patients with normal renal function at baseline, those with more advanced HIV disease are at higher risk of developing elevated Cr levels while taking TDF.
56 INCIDENCE AND RISK FACTORS FOR SEVERE ADVERSE EVENTS IN A PROSPECTIVE COHORT OF HIV-INFECTED ADULTS STARTED ON A PROTEASE INHIBITOR-CONTAINING THERAPY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 56)
X Duval1, V Journot2, T May3, C Charlois1, A Waldner4, C Merle de Boever6, C Barennes2, JM Ragnaud5, G Chêne2, C Leport1 and the APROCO Study Group
SAE after the initiation of HAART are frequent and related both to host (renal, hepatic tests and hepatitis co-infections) and treatments characteristics. Early occurrence of SAE in the course of therapy could involve for some of them a toxic mechanism, with decreasing risk over time.
57 GENDER AND RACE SUBGROUP ANALYSES IN A PROSPECTIVE STUDY OF HYPERLIPIDAEMIA IN ART-NAÏVE SUBJECTS TAKING TRIZIVIR (TZV), COMBIVIR (COM)/NELFINAVIR (NFV), OR STAVUDINE (D4T)/LAMIVUDINE (3TC)/NFV
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 57)
K Tashima1, P Kumar2, A Rodriguez-French3, M Thompson4, P Wannamaker5, V Williams5 and K Pappa5
Virologic and metabolic responses to the different regimens appear to vary by gender and race and further study is justified.
| July 2003 | Monday 14th . 14:30-16:30
Session 12OA - Oral Abstract
Mother-to-Child Transmission
Chair persons
Gunnel Biberfeld, Karolinska Institute, Stockholm, Sweden
Nicolas Meda, Centre MURAZ/OCCGE, Bobo-Dioulasso, Burkina Faso

58 TIMING OF MOTHER-TO-CHILD TRANSMISSION OF HIV-1 (MTCT) AND INFANT MORTALITY IN THE FIRST SIX MONTHS OF LIFE IN HARARE, ZIMBABWE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 58)
LS Zijenah1, LH Moulton2, P Iliff3, K Nathoo3, MW Munjoma4, K Mutasa3, L Malaba5, P Zvandasara4, BJ Ward6 and J Humphrey2–3 for the ZVITAMBO Study Group
In the first 6 months of life, IU and IP/ePP transmission contributed about 25% of the 30.7% MTCT. This is the first study with a large cohort, in the absence of antiretroviral intervention, to define contributions of the three modes of MTCT. Our data, in addition to serving as a historical comparison, may be useful in the designing and evaluating the efficacy of short course antiretroviral trials aimed at reducing MTCT in developing countries.
59 MATERNAL VIRAL LOAD AND CCR5 CO-RECEPTOR UTILIZATION: CRITICAL DETERMINANTS IN MOTHER-TO-CHILD HIV-1 TRANSMISSION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 59)
A Gormley1, B Weiser1, H Burger1, C Kitchen2, A Uppal1, R Moore1, C Brunner1 and S Philpott1
Although total viral load correctly predicted transmission in 94.3% of cases (OR=45.15, 95% CI=3.144-649.0), R5 viral load correctly predicted 98% (OR=496.77, 95% CI=3.044-999.0). One non-transmitting mother, whose total viral load exceeded one million copies, had an R5 load of only ∼100,000. Our results suggest that CCR5 plays an essential role in vertical transmission. Blockade of this receptor may provide an additional strategy to prevent motherto- child transmission.
60 FACTORS ASSOCIATED WITH PERINATAL HIV-1 TRANSMISSION IN MOTHERS AND NON-BREASTFED INFANTS RECEIVING ZIDOVUDINE (ZDV) PROPHYLAXIS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 60)
G Jourdain1,2, JY Mary3, S Le Coeur2,4, N Ngo-Giang-Huong1,2, K McIntosh5, K Kengsakul6, K Boonrod7 and M Lallemant1,2 for the perinatal HIV prevention trial group (PHPT)
Factors independently associated with early and late transmission despite ZDV may give insight on the mechanisms of transmission or of ZDV prophylaxis failure. The pathogenesis significance of elevated creatinine in relation to transmission needs to be investigated. Support: NIH R01 HD33326, IRD, Roche Diagnostics, GlaxoWellcome.
61 EFFECT OF PERINATAL ZIDOVUDINE TREATMENT ON THE EVOLUTION OF CELL-FREE HIV-1 IN BREAST MILK ON POSTNATAL TRANSMISSION, ANRS 049 DITRAME-VIRO STUDY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 61)
O Manigart1, M Crépin2, V Leroy3, N Meda1, D Valéa1, EN Janoff4, F Rouet2, L Dequae-Merchadoux3, F Dabis3, C Rouzioux5 and P Van de Perre1 for the ANRS 049 DITRAME Study Group
In a multivariate analysis performed on data from 80 women with complete information, increase of HIV-1 RNA in milk from day 45 to day 90 was significantly associated with postnatal transmission and with previous ZDV prophylaxis. The substantial risk of postnatal transmission of HIV-1 are significantly associated with HIV-1 RNA levels in milk. The rebound of HIV-1 RNA levels in milk after discontinuation of maternal ZDV, but before cessation of breasfeeding may introduce additional risk of postnatal transmission.
62 MULTICENTRE, RANDOMIZED CONTROLLED TRIAL, ASSESSING THE SAFETY AND EFFICACY OF NEVIRAPINE IN ADDITION TO ZIDOVUDINE FOR THE PREVENTION OF PERINATAL HIV IN THAILAND: PHPT-2 UPDATE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 62)
M Lallemant1,2, G Jourdain2, S Le Coeur2,3, JY Mary4, K McIntosh5, N Ngo-Giang Huong2, E Guerrin-Tran6, S Koetsawang6 and V Thaineua7
While adding NVP during labour and in the neonate to oral ZDV prophylaxis significantly decreases HIV transmission, the need for the infant NVP dose still needs to be established. Sponsors: NIH R01 HD39615, USA; ANRS 1208 and IRD, France; Ministry of Public Health, Thailand; Boehringer-Ingelheim (study treatment), Glaxo-Smith-Kline (ZDV), Roche Diagnostics (DNAPCR).
63 MORTALITY IN BREAST-FED AND FORMULA-FED CHILDREN BORN TO HIVINFECTED WOMEN IN A PMTCT PROJECT IN ABIDJAN (CÔTE D'IVOIRE): DITRAME PLUS ANRS 1202
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 63)
R Becquet1, L Becquet2, DK Ekouevi1,2, I Viho2, H Toure2, F Dabis1, M Timite-Konan3 and V Leroy1
In this context of an intensive counselling from birth, there is no evidence of a higher mortality in formula-fed HIV-uninfected children compared to those breast-fed. Further follow-up will allow us to compare these mortality rates with those in the general population in Abidjan.
64 INFANT FEEDING COUNSELLING IN THE REDUCTION OF MOTHER TO CHILD TRANSMISSION OF HIV IN MATERNAL AND CHILD HEALTH SETTINGS, NDOLA, ZAMBIA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 64)
E Muyunda2, N Ntombela2, J Tshiula2, F Munkonze2, N Dondi2, T Nyirenda2, M Mzumara2, M Barrett2, N Franklin2, C Kruger2, H Chiyota2, W Siasulwe3, M Lembalemba1, E Sakala1, A Banda1, S Kalibala3, N Rutenberg3 and S Geibel3
There is need to seriously consider realistic ways of incorporating replacement feeding in this community. If replacement feeding is unrealistic even in an urban area, it may not be different in the rural areas.
65 HIV-2 MOTHER-TO-CHILD TRANSMISSION RISK ASSESSED BY REAL TIME DNA PCR TECHNOLOGY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 65)
M Burgard1, S Blanche1, MJ Mayaux2, C Allisy3, N Ciraru4, G Firtion5, JM Retbi6 and C Rouzioux1 for the the ANRS Paediatric Cohort Study Group
HIV-2 rate of transmission was 0.5% (1/204; 95%CI:0-1.5%). Real time PCR is an easy and convenient method for HIV-2 diagnosis in neonates.
| July 2003 | Monday 14th . 14:30-16:30
Session 13OA - Oral Abstract
Reservoirs and Superinfections
Chair persons
Christine Rouzioux, Hospital Necker-Enfants Malades, Paris, France
Luc Perrin, Geneva University Hospital, Switzerland

66 PERSISTENCE OF HIV-1 MULTIDRUG RESISTANCE WITHOUT ANY ANTIRETROVIRAL TREATMENT 2 YEARS AFTER SEXUAL TRANSMISSION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 66)
C Delaugerre1, L Morand-Joubert2, O Picard2, ML Chaix3, AG Marcelin1, V Schneider4, A Krivine5, A Compagnucci6, C Katlama1, PM Girard2 and V Calvez1
Only multidrug resistant viruses, present in the source patients and well-adapted to the environment, were transmitted. In the index patients, an expansion of predominant MDR quasispecies and the ‘archival’ of all mutations were observed. These results explain the persistence of mutations and suggest the high difficulty to return to a wild-type viral population sensitive to an antiretroviral treatment. The treatment of index patients is limited and the major risk is the transmission of these multidrug resistant viruses.
67 THE LYMPHOCYTE HIV RESERVOIR IN PATIENTS ON PROLONGED HAART IS A MEMORY OF VIRUS EVOLUTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 67)
O Lambotte1, ML Chaix2, B Gubler3, N Nasreddine1, C Wallon1, C Goujard4, C Rouzioux2, Y Taoufik1,3 and JF Delfraissy1,4
The HIV lymphocyte reservoir is dynamic with a diversity mainly resulting from the successive archiving of plasma viruses circulating during the HIV infection course. The archiving of resistant virus must be taken into account in therapeutic decisions.
68 ENUMERATION OF LATENTLY INFECTED CD4+ T-CELLS FROM HIV-1 INFECTED PATIENTS USING AN HIV-1 ELISPOT ASSAY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 68)
V Baillat1, JM Fondere2, G Petit Jean2, V Perez2, J Reynes1 and JP Vendrell2,3
As each immunospot represents one HIV-1-secreting cell, the HIV-1 ELISPOT assay is an eligible assay to enumerate HIV-1 latently infected CD4+ T lymphocytes from peripheral blood. This sensitive assay could become a useful tool for precisely evaluating latently infected CD4+ T cell frequencies.
69 DEACETYLASE INHIBITORS AS CANDIDATE DRUGS TO PURGE LATENTLY HIV-1-INFECTED RESERVOIRS IN HAART PATIENTS? MECHANISTIC INSIGHTS INTO REGULATION OF VIRAL REPLICATION BY DEACETYLASE INHIBITORS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 69)
Y Collette1, V Quivy2, E Adam2, B Vire1, D Demonte2, V Bours3, J Piette3, D Olive1, A Burny2 and C Van Lint2
We identify a new regulatory link between DACi and NF-κB-dependent gene expression, which is not at the level of NF- κB/DAC interactions but at the level of IκBα cytoplasmic content. The physiological relevance of this TNFα-DACi synergism was shown on HIV-1 replication in both acutely and latently HIV-infected cells.
70 DUAL ROLE OF PROSTATIN IN INHIBITION OF INFECTION AND REACTIVATION OF LATENCY OF HUMAN IMMUNODEFICIENCY VIRUS IN PRIMARY BLOOD LYMPHOCYTES AND IN LYMPHOID TISSUE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 70)
A Biancotto1, JC Grivel2, M Pion1, F Gondois-Rey1, R Vigne1, S Brown3, LB Margolis2 and I Hirsch1
While prostratin stimulation restricts susceptibility of primary resting CD4 T cells to HIV at the virus cellentry and the reverse transcription levels, it efficiently reactivates expression of pre-integrated and integrated latent HIV-1. This dual role makes of prostratin an excellent candidate for the elimination of persistent HIV infection from latent reservoirs in HAART-treated patients.
71 RECOMBINATION FOLLOWING SUPER-INFECTION BY HIV-1
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 71)
G Fang1, B Weiser1,2, C Kuiken3, S Philpott1, S Rowland-Jones4, F Plummer5, J Kimani6, CH Chen1, B Shi1, R Kaul5,6, J Bwayo6, O Anzala6 and H Burger1,2
It illustrates that chronic infection with one strain may not provide protection against challenge from another. Recombination resulting from superinfection with diverse strains may pose problems for eliciting broad immune responses necessary for an effective vaccine.
72 HIV-1 SUPERINFECTIONS IN A COHORT OF COMMERCIAL SEX WORKERS IN BURKINA FASO AS ASSESSED BY A NOVEL AUTOLOGOUS HETERODUPLEX MOBILITY PROCEDURE, ANRS 1245 STUDY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 72)
O Manigart1,2, V Courgnaud2, O Sanou1, D Valéa1,2, N Nagot1,2, N Meda1,2, E Delaporte2, M Peeters2 and P Van de Perre2
In both women, retrospective analyses of stored samples showed acquisition of a second virus concomitant with an increasing plasma HIV RNA. Autologous HMA procedure, followed by acrylamide extraction of heteroduplexes, allowed identifying HIV-1 co- and super-infections in a large cohort study. HIV-1 super-infection is not an uncommon phenomenon.
73 PREVALENCE OF CO AND SUPER-INFECTION IN IVDUs
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 73)
S Yerly1, S Jost1, M Monnat2, A Telenti3, J-P Chave4, L Kaiser1, P Burgisser3 and L Perrin1
In recently infected IVDUs, the prevalence of co-infection is high (6%). In chronically infected IVDUs super-infection is not rare and has been observed in patients previously able to control HIV-1 infection due to another subtype.
| July 2003 | Monday 14th . 14:30-16:30
Session 14OA - Oral Abstract
AIDS-Related Diseases
Chair persons
Alaka Deshpande, JJ Hospital, Mumbai, India
Pierre-Marie Girard, Hospital Saint-Antoine, Paris, France

74 MULTICENTRIC CASTLEMAN’S DISEASE IN 70 HIV-INFECTED PATIENTS: A PROSPECTIVE COHORT STUDY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 74)
E Oksenhendler1, L Galicier1, L Gérard1, F Agbalika2 and V Meignin3
HIV/HHV8-associated MCD is a multiclonal virus-induced B cell lymphoproliferative disorder with plasmacytic differentiation. Evolution towards HHV8+NHL is unpredictable, although frequent if not constant.
75 RISK FACTORS FOR NON-HODGKIN LYMPHOMA IN HIV-INFECTED PATIENTS IN THE HAART ERA: A CASE CONTROL STUDY IN THE AQUITAINE COHORT (1996–2002)
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 75)
E Balestre1, F Bonnet1,2, R Thiébaut1,3, D Neau2, JL Pellegrin2 and F Dabis1 for the Groupe d’Epidémiologie Clinique du SIDA en Aquitaine (GECSA)
We have confirmed the protective effect of HAART but also of antiherpetic drugs on the risk of developing NHL. The role of HIV RNA need to be better assessed because it could represent a chronic simulating factor of B cells at the origin of monoclonal proliferation.
76 ELEVATED LEVELS OF SOLUBLE CD30 (sCD30) AND CD44 (sCD44) PRECEDE THE DEVELOPMENT OF AIDS-ASSOCIATED NON-HODGKIN’S B-CELL LYMPHOMA (AIDS-NHL)
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 76)
E Crabb Breen, M Epeldegui, S Fatahi, WJ Boscardin, R Detels and O Martínez-Maza
Serum levels of sCD30 and sCD44, molecules associated with B cell activation, were significantly increased preceding the clinical diagnosis of AIDS-NHL. A multifactorial analysis is underway to determine if sCD30 and/or sCD44 may be acting in concert with other B cell stimulatory molecules that have been shown to be elevated preceding the development of AIDS-NHL, to promote/reflect lymphomagenesis.
77 EBV SPECIFIC CTLs ARE CONSERVED IN MOST PATIENTS WITH EBV+ AIDS-ASSOCIATED LYMPHOMA DESPITE HIGH EBV VIRAL LOAD AND LOW CD8 COUNT
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 77)
L Galicier1, G Carcelain2, Y BenHadj Hmida2, J Gabarre3, JC Nicolas4, B Autran2 and E Oksenhendler1
The association of EBV+ NHL with high EBV viral load and low CD8 count suggests that loss of EBV control may play a direct role in the pathogenesis of AIDS lymphoma. However, although 30% of the patients had no detectable EBV-CTLs, more than 50% had normal T cell responses to both latent and lytic EBV peptides, whatever the EBV status of the tumour, suggesting that the loss of functional CTLs is not pivotal in the genesis of the majority of AIDS lymphomas.
78 PROGNOSTIC FACTORS OF KAPOSI’S SARCOMA IN THE ERA OF HAART
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 78)
V Martinez1–2, E Caumes1,I Gorin2, D Salmon-Ceron3, C Katlama1, F Bricaire1 and N Dupin2
Patients naïve of antiretroviral therapy or with progression of KS at months 6 and 12 have an additional risk of progression of KS. Moreover, our results shown a relationship between remission of KS and supressed viral load under HAART.
79 SYPHILIS AND THE CENTRAL NERVOUS SYSTEM (CNS) IN HIV INFECTED PATIENTS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 79)
S Hopkins, H McDermott, F Lyons, C Bergin and F Mulcahy
50% of lumbar punctures were not required in this cohort if CS and sTPPA >5120 were utilized for assessment of NS risk. This study provides clinical criteria for evaluating syphilis in HIV-positive individuals.
80 NATURAL HUMAN CYTOMEGALOVIRUS (HCMV) DNA POLYMERASE POLYMORPHISM: CONSEQUENCE ON GENOTYPIC DIAGNOSIS OF ANTIVIRAL DRUG RESISTANCE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 80)
AM Fillet1, L Auray1, S Alain4, K Gourlain1, F Najioullah5, S Gouarin6, J Carquin7, I Garrigues8, N Houhou2, D Thouvenot5, BM Imbert9, MC Mazeron2 and the ANRS Cytomegalovirus Study Group
Both mutations A885T and S655L were frequently observed, as previously published (Chou 1999). In contrast, S633F, T691A and A692S have never been described. All mutations occurred outside of conserved functional domains where resistance mutations have been identified. Results showed no distinctive clustering with geographical origin.
81 FACTOR ASSOCIATED AND PROGNOSTIC DETERMINANTS OF TOXOPLASMIC ENCEPHALITIS IN THE HAART ERA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 81)
D Larussa1, P Lorenzini1, A Cingolani2, S Bossolasco3, MG Finazzi4, M Bongiovanni5, B Vigo6, S Grisetti1, G Guaraldi7, B Gigli, A Mariano8, ER Dallenogare9, A Ammassari2, A d’Arminio Monforte5, P Cinque3 and A Antinori1 for the Italian Registry Investigative Neuro AIDS (IRINA)
TE remains the main neurological disorder even in the HAART era. Occurrence of TE as clinical progression during HAART negatively affects clinical response, even if high rates of survival were observed independently from HAART exposure before diagnosis.
| July 2003 | Monday 14th . 14:30-16:30
Session 15OA - Oral Abstract
Epidemiology, Morbidity and Mortality
Chair persons
Charles Gilks, WHO, Geneva, Switzerland
Harold W. Jaffe, CDC, Atlanta, USA

82 HIV TRANSMISSION DURING PRIMARY VERSUS SECONDARY HIV INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 82)
M Xiridou1, M Kretzschmar2, R Geskus1, J De Wit1,3 and R Coutinho1,4
Therefore, early treatment of PHI has only a limited impact on the spread of HIV. However, during a period with high incidence, primary infections account for a larger fraction of new infections and early treatment may have a major impact.
83 HORMONAL CONTRACEPTION AND RISK OF HIV-1 ACQUISITION: RESULTS OF A 10-YEAR PROSPECTIVE STUDY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 83)
L Lavreys1-2, JM Baeten1, HL Martin Jr3, JK Kreiss1, K Mandaliya4, J Ndinya-Achola2 and J Overbaugh5
Use of hormonal contraception is associated with a significantly increased risk of HIV-1 acquisition. Condoms should be rigorously promoted in women at risk for HIV-1 and who use hormonal contraception.
84 PREVALENCE OF UNDIAGNOSED HIV INFECTION IN FEBRILE PATIENTS PRESENTING TO AN EMERGENCY DEPARTMENT IN SOUTH-EASTERN USA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 84)
AC Weintrob1, AML Anderson1, C Seshadri1, LB Caram1, MG Kerkau2, SA Fiscus2 and CB Hicks1
A significant number of people with undiagnosed HIV infection present to the Duke ED. As many patients use the ED as their primary source of medical care, improved strategies for HIV testing are required in this setting.
85 IMMUNOLOGICAL AND CLINICAL RESPONSES TO HAART OVER 50 YEARS OF AGE, RESULTS FROM THE FRENCH HOSPITAL DATABASE ON HIV
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 85)
S Grabar1,2, I Kousignian2, A Sobel3, P Enel4, C Jung3 and D Costagliola2
Patients over 50 years old exhibited an immune response after HAART. However, their CD4 cells reconstitution was significantly slower than in younger patients. This may explain why older patients have a higher risk of clinical progression.
86 THE IMPACT OF THE EMERGENCE OF ANTIRETROVIRAL RESISTANCE IN THE FIRST YEAR ON SURVIVAL IN SUBSEQUENT YEARS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 86
RS Hogg, CS Alexander, B Yip, W Dong, T Mo, J Woodward, B Wynhoven, L Ting, MV O’Shaughnessy, JSG Montaner and R Harrigan
In conclusion, these results indicate that although the emergence of resistance remains relatively low after the first year on therapy, persons who exhibited reduced sensitivity to NNRTIs during this period appear at greater risk of death.
87 MORTALITY DUE TO HEPATITIS C-RELATED LIVER DISEASE IN HIV-INFECTED PATIENTS IN FRANCE IN 2001 (MORTAVIC 2001 STUDY)
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 87
E Rosenthal1, M Poirée1, C Pradier2, C Perronne3, D Salmon-Ceron4, L Geffray5, RP Myers6, P Morlat7, G Pialoux8, S Pol9 and P Cacoub10 for the GERMIVIC Joint Study Group
In the post-HAART era, ESLD due to HCV is a growing cause of mortality in HIV-infected patients. Increased longevity attributable to HAART, and a higher prevalence of alcohol consumption, are likely involved in this trend.
88 CAUSES OF DEATH IN HIV-INFECTED ADULTS IN THE ERA OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART): THE FRENCH SURVEY MORTALITÉ 2000
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 88)
C Lewden1, S Bévilacqua2, F Bonnet3, L Héripret4, D Salmon5, P Morlat3, T May2, D Costagliola6, E Jougla7, G Chêne1 and the Mortalité 2000 Study Group
In 2000, half of deaths in HIV-infected patients were still AIDS-related. Nevertheless changes in the causes of death in HIV-infected persons leads to a diversification of places and modalities of care at the end of life in this population. This has to be taken into account in surveys describing the distribution of the causes of death.
89 MORTALITY AFTER STARTING HIGHLY ACTIVE ANTIRETROVIRAL THERAPY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 89)
A van Sighem1, A Ghani2, P Reiss3, I Gyssens4, K Brinkman5, J Lange3, I van Valkengoed1, L Gras1, F de Wolf1,2
The reduction in overall mortality is due to a reduction in HIV-related mortality. Non-HIVrelated mortality remains higher than in the general population. The lack of any change in non-HIV-related mortality suggests that toxicity has not yet become a major risk factor for death.
| July 2003 | Monday 14th . 14:30-16:30
Session 16OA - Oral Abstract
Virus Entry and Early Steps of Virus Cycle
Chair persons
Quentin Sattentau, Oxford University, UK
Fernando Arenzana, Institut Pasteur, Paris, France

90 INTERACTIONS BETWEEN HIV AND THE DUFFY ANTIGEN RECEPTOR FOR CHEMOKINES (DARC)
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 90)
SJD Neil, D Marchant, A McKnight and RA Weiss
Our results indicate that HIV binds to DARC and imply a role for DARC in the sequestration of virus on circulating RBCs, as well as potentially affecting plasma levels of DARC ligands such as RANTES.
91 HIV-1 EXPLOITS AN ENV-INDUCED SYNAPSE IN CD4+ T-CELLS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 91)
CL Jolly and QJ Sattentau
We propose that ‘virological synapse’ formation is an actin-dependent process that facilitates cellto- cell transfer of infectious viral material, and may be an important mechanism of viral dissemination in densely-packed lymphoid tissue.
92 HIV-1 MEDIATED SIGNAL TRANSDUCTION THROUGH CCR5 ALLOWS INFECTION OF RESTING MEMORY T-CELLS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 92)
J Vasudevan1, A Matthews1,2, A Meek1 and D Camerini1,2
Preliminary QPCR results show a decrease in completion of reverse transcription and 2-LTR circle production in RMT infected with R5 or X4 HIV-1. Our data implicate R5 HIV-1 mediated signalling via CCR5 in the establishment of infection in normal, resting memory T cells. In contrast, X4 HIV-1 infection is blocked at a post-entry step in RMT. Signalling through Gái and Gás do not appear to play a role in the establishment of infection, but the downstream signalling molecules PI3K and c-Src may be important mediators of R5-HIV-1 infection of RMT.
93 HIV-1 INFECTIVITY REFLECTS A DYNAMIC BALANCE BETWEEN FUSION AND ENDOCYTOSIS IN HUMAN CD4 T LYMPHOCYTES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 93)
E Schaeffer1,2 and WC Greene1
In conclusion, these studies reveal an intriguing compensatory link between fusion and endocytosis of HIV-1, which in T cells is governed by the common involvement of CD4 receptors in both entry pathways.
94 EFFICIENCY OF HOST CELL ENTRY IS THE DOMINANT FACTOR MEDIATING EX VIVO HIV-1 FITNESS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 94)
DM Moore, AJ Maroszan, SC Ball, A Abraha, K Demers and EJ Arts
Preliminary data also suggests that increased fitness or efficiency of host cell entry is related to a reduced sensitivity to entry inhibitors such as AOP- or PSC-RANTES, T-20, T-1249 and C34. This study provides evidence that host cell entry is important for pathogenesis and should remain an important target for anti-HIV-1 drugs.
95 POTENT SUPPRESSION OF HIV-1 INFECTIVITY BY LENTIVIRAL VECTORS INTERFERING WITH THE VIRUS-INDUCED CD4 DOWN-MODULATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 95)
J Lama1,2 and B Groschel1
Lentiviral vectors expressing CD4Δcyt were efficient at blocking HIV infectivity in a variety of cells expressing different ranges of surface- CD4, and also in CD4-positive primary lymphocytes. These results provide proof-of-principle that selective inhibition of the virusinduced CD4 down-modulation may constitute a suitable strategy to halt HIV replication.
96 EXISTENCE OF TWO DISTINCT MECHANISMS FOR THE BINDING OF HIV-1 ENVELOPE GLYCOPROTEINS TO DC-SIGN
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 96)
L Vachot, Y Ataman-Onal and B Verrier
This result indicates that DC-SIGN binding to HIV-1 envelope glycoproteins could occur by two mechanisms through the recognition of glycans or through interaction with protein core. Those results provide new insight for the design of Env immunogens able to induce neutralizing antibodies for DC-SIGN/gp120 interaction.
97 SENSITIVITY OF HIV-1 SUBTYPE C ISOLATES TO THE FUSION INHIBITOR T-20
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 97)
T Cilliers, T Patience, MA Papathanasopolous, L Morris
These data suggest that T-20 appears to be effective against HIV-1 subtype C isolates and may be useful for treating patients infected with this subtype.
| July 2003 | Monday 14th . 17:00-18:00
Session 17CO - Controversy
Is There a Prospect for Therapeutic Vaccination?
Moderator
Michael Lederman, Case Western Reserve University/University Hospitals of Cleveland, USA
98* PRO SPEAKER
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 98)
Yves Lévy, Hospital Henri-Mondor, Créteil, France
Abstract not available
99* CON SPEAKER
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 99)
Jonathan Weber, Imperial College of Science, Technology and Medicine
Abstract not available
| July 2003 | Monday 14th . 17:00-18:00
Session 18CO - Controversy
Should We Modify Antiretroviral Treatment based on Cardiovascular Risk?
Moderator
David Cooper, University of New South Wales, Sydney, Australia
100* PRO SPEAKER
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 100)
Marc van der Valk, Academic Medical Center, University of Amsterdam, The Netherlands
Abstract not available
101* CON SPEAKER
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 101)
Sam Bozzette, University of California, San Diego, USA
Abstract not available
| July 2003 | Monday 14th . 17:00-18:00
Session 19CO - Controversy
The Non-Public Sector Is More Important Than Governments for Expanding Access to Treatment in the Developing World
Moderator
ElHadj Sy, Global Fund to Fight AIDS, Tuberculosis and Malaria, Geneva, Switzerland
102* PRO SPEAKER
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 102)
Alex G. Coutinho, The AIDS Support Organisation (TASO), Kampala, Uganda
Abstract not available
103* CON SPEAKER
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 103)
Daniel Berman, Médecins Sans Frontières, Geneva, Switzerland
Abstract not available
| July 2003 | Monday 14th . 17:00-18:00
Session 20CO - Controversy
Viral Subtypes Are of Major Relevance for HIV Vaccines
Moderator
William Malegapuru Makgoba, University of Natal, Durban, South Africa
104* PRO SPEAKER
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 104)
Max Essex, Harvard AIDS Institute, Boston, USA
Abstract not available
105* CON SPEAKER
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 105)
Sarah Rowland-Jones, Weatherall Institute of Molecular Medicine, Oxford University, UK
Abstract not available
| July 2003 | Monday 14th . 18:00 - 19:30
Session 21PL - Plenary
Chair persons
Christine Katlama, University Hospital Pitié-Salpêtrière, Paris, France
Giuseppe Pantaleo, Lausanne University Hospital, Switzerland

106* NEW ANTIRETROVIRAL DRUGS AND THERAPEUTIC STATEGIES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 106)
Patrick Yéni, Hospital Bichat, Paris, France
Abstract not available
107* HIV VACCINE RESEARCH: THE STATE OF THE SCIENCE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no.
Lawrence Corey, University of Washington, Seattle, USA
Abstract not available
| July 2003 | Tuesday 15th . 10:00-12:00
Session 22FO - Forum
The Scaling-Up of Antiretroviral Therapy in Developing Countries
Chair persons
Papa Salif Sow, Dakar University Teaching Hospital, Dakar, Senegal
Paulo Teixeira, Brazilian STD/AIDS Program, Ministry of Health, Brasilia, Brazil

108* UPDATE ON THE USE OF ANTIRETROVIRALS IN COUNTRIES WITH LIMITED RESOURCES: FROM PILOT STUDIES TO PUBLIC HEALTH REALITIES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 108)
Papa Salif Sow, Dakar University Teaching Hospital, Senegal
Abstract not available
109* THE CHALLENGES OF EXPANDING ACCESS TO ANTIRETROVIRALS WORLDWIDE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 109)
Paulo Teixeira, Brazilian STD/AIDS Program, Ministry of Health, Brasilia, Brazil
Abstract not available
110 SAFETY AND IMMUNOLOGICAL EFFECTIVENESS OF SIMPLIFIED FIXED-DOSE COMBINATION OF NEVIRAPINE-BASED HAART AMONGST INDIAN PATIENTS: EXTENDED FOLLOW-UP DATA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 110)
S Pujari1, A Patel2, E Naik3, J Patel2, K Patel2, A Mane1, S Bhagat1 and A Vashsihtha1
The fixed dose combination of NVPbased HAART showed good safety and durable immunological improvement in this largest observational study till date from India. Simplifying therapy may be one of the reasons explaining this remarkable success.
111 WHAT HAPPENS WHEN A RESEARCH PROJECT CLOSES: HIV INCIDENCE, MORTALITY, AND PERCEPTIONS IN A COUPLES’ COHORT IN LUSAKA, ZAMBIA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 111)
E Shutes1,3 and the Rwanda/Zambia HIV Research Group1,3
Self-reported and objective data confirmed that risk reduction was maintained in the absence of regular follow-up. The most negative perceived impact on study participants was the loss of health care, which coincided with an increase in mortality rates. HIV research projects should make transition plans and establish functional health referral mechanisms for study participants when research funding ends.
112 TREATMENT OF HIV DISEASE WITH HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART) IN CHIRADZULU DISTRICT, MALAWI
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 112)
N Durier
Results are showing the feasibility of large-scale HAART in under-privileged areas. Our experience is also being incorporated into the design of the national HIV/ARV programme.
113 COST IMPLICATIONS OF PROVIDING SCALED-UP HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART) IN A MIDDLE INCOME MICROSTATE: THE BARBADOS EXPERIENCE IV
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 113)
SA Adomakoh1, NKP Adomakoh2, A Gaskin1, TC Roach3, A Abayomi3 and HS Fraser1
The results indicate a cost shift from inpatient to outpatient care in the first year of HAART. However projections showed with planned increases in support staff and VCT uptake, earlier diagnosis of AIDS patients and increased provision of HAART, net cost is likely to increase to $388 per month. To optimize beneficial returns in terms of health gains and increased productivity, follow-up support programmes that encourage return to work and skills training of PWHA must operate in tandem with HAART treatment services.
| July 2003 | Tuesday 15th . 10:00-12:00
Session 23FO - Forum
Salvage Therapy
Conveners
Robert L. Murphy, Northwestern University Medical School, Chicago, USA
Schlomo Staszewski, J.W. Goethe University, Frankfurt am Main, Germany

114* STATE-OF-THE-ART TALK: NOVEL STRATEGIES FOR SALVAGE THERAPY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 114)
Schlomo Staszewski, J.W. Goethe University, Frankfurt am Main, Germany
Abstract not available.
115* STATE-OF-THE-ART TALK: NEW ANTIRETROVIRAL AGENTS AND THEIR OPTIMAL USE IN SALVAGE THERAPY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 115)
Robert L. Murphy, Northwestern University Medical School, Chicago, USA
Abstract not available.
116 ANALYSIS OF VIROLOGICAL RESPONSE OF ENFUVIRTIDE IN TORO: IMPLICATIONS FOR PATIENT MANAGEMENT
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 116)
J Montaner1, R DeMasi2, J Delehanty2, J Chung3, Z Gafoor2 and M Salgo3 on behalf of the TORO 1 and TORO 2 Study Groups
While the comparative efficacy of ENF+OB over OB alone has previously been established, these results suggest that the virological response to ENF+OB therapy is directly related to the activity of the background regimen and improved responses were observed in less advanced and less-experienced patients.
117 ANTIVIRAL EFFICACY, METABOLIC CHANGES AND SAFETY OF ATAZANAVIR (ATV) VERSUS LOPINAVIR/RITONAVIR (LPV/RTV) IN COMBINATION WITH TWO NRTIs IN PATIENTS WHO HAVE EXPERIENCED VIROLOGICAL FAILURE WITH PRIOR PI-CONTAINING REGIMEN(S): 24-WEEK RESULTS FROM BMS AI424-043
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 117)
L Nieto-Cisneros1, C Zala2, WJ Fessel3, J Gonzalez-Garcia4, C Cohen5, R McGovern6, E Adler7 and C McLaren6
Significant reductions in HIV RNA and robust increases in CD4 cell counts were observed in this PI-failing, ARV-experienced population. While non-boosted ATV demonstrated less antiviral efficacy than the boosted LPV/RTV regimen, ATV had a more favourable lipid profile. ATV may be an option for some ARV-experienced patients, e.g., where lipid management is a priority.
118 EFFICACY AND SAFETY OF ATAZANAVIR (ATV) WITH RITONAVIR (RTV) OR SAQUINAVIR (SQV) VS LOPINAVIR/RITONAIR (LPV/RTV) IN COMBINATION WITH TENOFOVIR (TFV) AND ONE NRTI IN PATIENTS WHO HAVE EXPERIENCED VIROLOGIC FAILURE TO MULTIPLE HAART REGIMENS: 16-WEEK RESULTS FROM BMS AI424-045
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 118)
R. Badaro1, E. DeJesus2, A. Lazzarin3, J. Jemsek4, B. Clotet5, R. Wilber6, A. Thiry6, A. Rightmire6
In this highly ARV-experienced population, the efficacy of ATV/RTV QD is similar to LPV/RTV BID through 16 weeks. ATV, when boosted with RTV or combined with SQV is safe, well tolerated and with a more favorable lipid profile than LPV/RTV.
119 FAILURE OF STRUCTURED TREATMENT INTERRUPTION (STI) TO CONFER BENEFIT IN THE SETTING OF TREATMENT FAILURE: CPCRA 064 RESULTS BY BASELINE CD4 COUNT AND PHENOTYPIC SENSITIVITY SCORE (PSS) SUBGROUPS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 119)
J Lawrence1, K Huppler Hullsiek2, D Mayers3, D Abrams1, R Reisler4, L Crane5, B Schmetter6, T Dionne7, J Saldanha8, M Jones1 and J Baxter9 for the CPCRA 064 Study Team for the Terry Beirn Community Programs for Clinical Research on AIDS
Subgroup analyses by baseline CD4 count and PSS show similar results to the full cohort, suggesting that STI in these subpopulations does not confer immunological or virological benefit.
| July 2003 | Tuesday 15th . 10:00-12:00
Session 24FO - Forum
Viral Molecular Pathogenesis
Conveners
Olivier Schwartz, Institut Pasteur, Paris, France
Didier Trono, Geneva University Hospital, Switzerland

120* STATE-OF-THE-ART TALK: HIV AND DENDRITIC CELLS: VIRUS SPREAD AND ANTIGEN PRESENTATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 120)
Olivier Schwartz, Institut Pasteur, Paris, France
Abstract not available.
121* STATE-OF-THE-ART TALK: INNATE INTRACELLULAR ANTIRETROVIRAL DEFENSES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 121)
Didier Trono, Geneva University Hospital, Switzerland
Abstract not available.
122 IDENTIFICATION OF TIP47 AS THE FIRST CELLULAR CO-FACTOR INVOLVED IN THE RETROGRADE TRANSPORT OF THE HIV-1 ENVELOPE TO THE TRANS-GOLGI NETWORK: EFFECT ON THE ENV INCORPORATION AND ON HIV-1 INFECTIVITY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 122)
G Blot1, K Janvier1, S Le Panse2, R Benarous1 and C Berlioz-Torrent1
Mutation of the Y802W803 di-aromatic motif abolished both targetting to the TGN as well as interaction with TIP47 and decreased Env cell surface expression. These data support the view that binding of TIP47 to HIV-1 Env facilitates its delivery to the TGN. Lastly, we show that virus mutated in the Y802W803 motif is poorly infectious and presents a defect in Env incorporation, supporting a model in which retrograde transport of Env is implicated in optimization of fully infectious HIV-1 production.
123 MECHANISM OF ACTION OF THE HIV-1 VIF ACCESSORY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 123)
BR Cullen1,2, HP Bogerd1 and B Doehle2
The mouse homologue of APOBEC3G also specifically blocks HIV-1 replication but in this case the inhibitory effect is not relieved by co-expression of HIV-1 Vif. This result strongly suggests that APOBEC3G-mediated inhibition of HIV-1 replication may play a key role in determining the species tropism of HIV-1. We are currently examining the biological activity of a range of human and simian proteins related to APOBEC3G and are examining the importance of these factors in determining HIV-1 tissue and species tropism.
124 LEDGF/p75 A CELLULAR CO-FACTOR OF HIV-1 INTEGRASE ESSENTIAL FOR HIV-1 REPLICATION: A NOVEL TARGET FOR ANTI-HIV-1 DRUG DISCOVERY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 124)
S Emiliani1, JC Rain2, M Maroun1, F Martin2, E Segeral1, L Selig2, P Legrain2 and R Benarous1
We have isolated several Integrase mutants that have lost interaction with LEDGF/p75. The effects of these mutants on viral replication are presently under investigation. LEDGF/p75, as a key cellular factor for HIV-1 replication, represents a potential target for the development of novel anti HIV-1 drugs.
125 TAT STIMULATES COTRANSCRIPTIONAL CAPPING OF HIV mRNA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 125)
TM Rana and YL Chiu
Cotranscriptional capping of HIV mRNA is strongly stimulated by Tat and this stimulation requires the C-terminal segment of Tat that mediates its direct binding to Mce1. Our findings implicate cap formation as a component of an elongation checkpoint critical to HIV gene expression.
| July 2003 | Tuesday 15th . 10:00-12:00
Session 25FO - Forum
Pharmacology of Antiretroviral Agents for Managing Treatment
Conveners
Charles W. Flexner, Johns Hopkins University School of Medicine, Baltimore, USA
David Back, University of Liverpool, UK

126* STATE-OF-THE-ART TALK: THE NEW BIOLOGY OF DRUG TRANSPORTERS AND DRUG METABOLIZING ENZYMES: IMPLICATIONS FOR CLINICAL PRACTICE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 126)
Charles W. Flexner, Johns Hopkins University School of Medicine, Baltimore, USA
Abstract not available
127* STATE-OF-THE-ART TALK: THE IMPACT OF GENDER, ETHNICITY AND CO-INFECTIONS ON ANTIRETROVIRAL PHARMACOKINETICS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 127)
David Back, University of Liverpool, Liverpool, UK
Abstract not available
128 SEX DIFFERENCES IN VIROLOGICAL RESPONSE AND SAQUINAVIR (SQV) PHARMACOLOGY IN ACTG 359
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 128)
CV Fletcher1, H Jiang2, RC Brundage3, EP Acosta4, R Haubrich5, D Katzenstein6, S Snyder7 and R Gulick8
A significantly greater proportion of females had VL ≤500 c/ml at wk 16 than males. This finding may be attributed to a sex difference in SQV conc, as females had higher AUCs than males.
129 PLASMA NELFINAVIR CONCENTRATIONS ARE SIGNIFICANTLY LOWER IN PREGNANCY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 129)
F Wit2, J Nellen1, A Bergshoeff3, D Burger3, M Godfried1, K Boer1, J Lange1 and J Prins1
Non-pregnant females have similar NFV CRs as the male white reference population. Race did not influence the NFV CR in women. Pregnancy is associated with markedly decreased NFV concentrations. Drug levels in pregnant women should be carefully monitored.
130 EXPRESSION AND LOCALISATION OF THE MULTIDRUG RESISTANCE TRANSPORTER IN PLACENTAS FROM HIV-INFECTED MOTHERS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 130)
M Camus1, S Gil1,C Deloménie2, A Devocelle1, I Perrot3, MC Dauge3 and R Farinotti1
P-glycoprotein (P-gp), encoded by mdr1 gene, is a transmembrane protein involved in multidrug resistance (MDR) phenomenon by expulsing drugs out of cells. HIV protease inhibitors which are substrates of P-gp are now more frequently administered to HIVinfected women during pregnancy.
131 PREPARING FOR HIV-1 THERAPY IN SOUTH AFRICA: WILL HOST POLYMORPHISMS IN MDR1 AND CYP3A4 INFLUENCE THERAPEUTIC OUTCOME?
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 131)
PK Chelule1, A Mosam2, M Gordon1, T Palanee1, T Page1, HM Coovadia3 and S Cassol1,4
Recent studies have reported substantial differences in the frequency and distribution of MDR1 and CYP3A4 polymorphisms among different racial groups and suggested that these differences may contribute to HIV-1 treatment failure.
| July 2003 | Tuesday 15th . 10:00-12:00
Session 26FO - Forum
Host Genetic Determinants of HIV Disease
Conveners
Mary Carrington, NCI-FCRDC, Frederick, USA
Amalio Telenti, University Hospital of Lausanne, Switzerland

132* STATE-OF-THE-ART TALK: DISSECTING THE EFFECTS OF HLA AND KIR GENETIC POLYMORPHISM ON HIV DISEASE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 132)
Mary Carrington, NCI-FCRDC, Frederick, USA
Abstract not available
133* INVITED TALK: HIV MUTATIONAL ESCAPE FROM CTL RESPONSES AND ANTIRETROVIRALS: PARALLELS AND DIFFERENCES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 133)
Simon Mallal, Royal Perth Hospital, Australia
Abstract not available
133A* STATE-OF-THE-ART TALK: GENETIC PREDICTION OF HIV DISEASE PROGRESSION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 133A)
Amalio Telenti, University Hospital of Lausanne, Switzerland
Abstract not available
134 A-B-O BLOOD GROUPS AND HIV-1 INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 134)
SJD Neil, S Magre, Á McKnight and RA Weiss
Incorporation of ABO antigens by HIV-1 may affect transmission of virus between individuals of discordant blood groups by interaction with host natural antibody and complement.
135 INFLUENCE OF CHROMOSOME 3p21-22 CHEMOKINE RECEPTOR VARIANTS AND HAPLOTYPES ON HIV-1/AIDS PATHOGENESIS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 135)
P An1, GW Nelson1, SJ O'Brien2 and CA Winkler1
The gene encoding CCR5, required for cell entry by the R5 strains of HIV-1, occurs in a cluster of five chemokine receptor genes on C3p21.
136 LARGE SCALE MICROARRAY ANALYSIS REVEALS NEW ASPECTS OF EARLY CD4 RECONSTITUTION AFTER INITIATION OF ANTIRETROVIRAL THERAPY IN NAÏVE HIV-POSITIVE PATIENTS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 136)
D Puthier1, F Boutboul2, O Pelé2, S Pierre-François3, B Loriod1, C NGuyen1 and B Autran2
This CD4 cell gene expression profiling during the first wave of CD4 reconstitution during HAART in naïve HIV-infected patients suggests that the major early increase in CD4 cell count involves extinction in the very early cellular machinery of activation that was overexpressed during the natural course of the disease.
137 MANNOSE-BINDING LECTIN (MBL) ALLELES IN SUB-SAHARAN AFRICANS AND RELATIONSHIP WITH SUSCEPTIBILITY TO INFECTIONS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 137)
LE Mombo1,2, CY Lu1, S Ossari1, I Bedjabaga1, L Sica1, R Krishnamoorthy2 and C Lapoumeroulie2
Our data plus those in the literature suggest that individuals who are homozygous for the mutant MBL alleles display increased susceptibility to infections. Interestingly, we found that individuals who are heterozygous for MBL mutations are much less susceptible to infections than those who are homozygous for the wild-type MBL allele.
| July 2003 | Tuesday 15th . 14:30-16:30
Session 28OA - Oral Abstract
Clinical Science
Chair persons
Julio S.G. Montaner, University of British Columbia, Vancouver, Canada
Praphan Phanuphak, Chulalongkorn University, Bangkok, Thailand

138 COST-EFFECTIVENESS OF GENOTYPIC RESISTANCE TESTING IN PATIENTS WITH EXTENSIVE PRIOR ANTIRETROVIRAL EXPOSURE: MODELLING RESULTS FROM THE NARVAL TRIAL
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 138)
Y Yazdanpanah1, M Vray2, JL Meynard3, E Losina4, L Morand-Joubert3, SJ Goldie5, C Dalban2, MC Weinstein5, PM Girard3 and KA Freedberg6
In patients with extensive prior antiretroviral exposure failing HAART, genotypic resistance testing appears to be cost-effective when explicitly incorporating the benefits from sparing therapeutic options for future use.
139 IS A TOTAL LYMPHOCYTE COUNT A SURROGATE MARKER FOR ABSOLUTE CD4+ CELLS COUNT AMONG HIV-1 INFECTED PATIENTS IN NAIROBI, KENYA?
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 139)
J Kimani1, E Irungu1, P Thottingal1-2, J Njeri1, A Kariri1, C Wachihi1 and FA Plummer1-2
A total lymphocyte count was found to be a poor surrogate marker for absolute CD4+ cells counts in our settings and should be discouraged. Although a definitive study is ongoing, research on newer and affordable CD4+ cells enumeration technologies should be the major priority. However, these findings and the poor infrastructure for monitoring HIV management in most developing countries should not be viewed as a barrier to the scaling-up initiatives for antiretroviral therapy.
140 PATTERNS OF HIV-1 RESISTANCE MUTATIONS AFTER 8 WEEKS OFF THERAPY IN PATIENTS ENROLLED IN THE RANDOMIZED,OPEN-LABEL, ANRS 106 – WINDOW TRIAL
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 140)
J Izopet1, P Tangre2, B Marchou1, I Charreau2, K Sandres-Sauné1, V Eliette2, JM Ragnaud3,C Katlama4, T May5, PM Girard6, JP Aboulker2, JM Molina7 and the ANRS 106 Study Group
Datas show that the presence of drug-resistant virus in plasma at w8 didn’t influence the virus response after treatment resumption. Long term impact of HIV- 1 resistance mutations will be assessed over successive cycles.
141 EVALUATION OF QUANTITATIVE HIV LOAD ASSAY BASED ON PLASMA VIRION REVERSE TRANSCRIPTASE ACTIVITY IN WEST AFRICA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 141)
J Braun1, JP Lombart2, J-C Plantier1, MF Hellot3, E Tuaillon1, M Gueudin1, F Damond4, A Malmsten5,6, GE Corrigan6 and F Simon1
Our data support the use of plasma RT-activity quantification assay as a simple, cheap and reliable alternative for HIV viral load determination.
142 RESIDUAL CIRCULATING RESERVOIR (PBMC HIV-1 DNA) ESTIMATED AFTER 3 YEARS OF EFFICIENT HAART IS PREDICTED BY VIROIMMUNOLOGICAL STATUS BEFORE THERAPY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 142)
M Burgard1, P Flandre2, I Garrigue3, P Colson4, O Guisthau5, K Saune6, A Vabret7, V Chams-Harvey8, G Bargues9, B Amellal10, I Pellegrin3, C Tamalet4, A Ruffault5, J Izopet6, D Descamps8, K Gourlain10, JM Seigneurin9 and C Rouzioux1 for the ANRS HIV Quantification Group
HIV-1 DNA in PBMC remained high despite long-term undetectable viral replication, suggesting a weak impact of HAART on viral reservoir; even after long term antiretroviral therapy, HIV-1 DNA remained a significant reflect of the initial viro-immunological status before therapy.
143 BASELINE HIV-1 V3 LOOP SEQUENCES AS PREDICTOR OF IMMUNOLOGIC DECLINE AND MORTALITY IN A LARGE COHORT STARTING INITIAL HAART THERAPY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 143)
PR Harrigan1,2, WY Dong1, B Yip1, ZL Brumme1, B Wynhoven1, N Hoffman3, R Swanstrom3,T Mo1, MA Jenson4, JI Mullins4, RS Hogg1 and JSG Montaner1,2
Baseline V3 loop sequence data appears to provide additional prognostic information regarding future response to HAART.
144 CD4+ CELL INCREASE TO HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART) AT ONE YEAR IS PREDICTIVE OF CLINICAL OUTCOME DESPITE INCOMPLETE VIRAL SUPPRESSION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 144)
M Loutfy1, S Walmsley2, C Mullin3, G Perez4 and J Neaton3 for the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) and the Canada Trials Network (CTN)
Even a modest CD4 cell increase after 12 m of HAART confers clinical benefit in HIV-infected pts with incomplete virologic suppression, as demonstrated by the steady decrease in clinical progression for each incremental increase in CD4 response.
145 THE EFFECT OF HAART INTERRUPTIONS ON CLINICAL PROGRESSION: EVIDENCE FROM ICONA COHORT
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 145)
A d'Arminio Monforte1, A Cozzi-Lepri2, R Murri3, R Novati4, A Antinori5, C Arici6, V Colangeli7, A De Luca3, N Ladisa8, E Girardi5 and M Moroni1 for the ICoNA Study Group
These data suggest that unsupervised HAART TIs of ≥12 weeks are associated with clinically significant increased risk of AIDS or death.
| July 2003 | Tuesday 15th . 14:30-16:30
Session 29OA - Oral Abstract
Viral Dynamics and Fitness
Chair persons
Jean-Luc Darlix, Ecole Normale Supérieure de Lyon, France
Marc A. Wainberg, McGill University AIDS Centre, Montreal, Canada

146 QUANTITATING HIV DNA FROM REVERSE TRANSCRIPTION TO INTEGRATION IN VIVO
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 146)
JP Vartanian1, R Suspène1, D Guétard1,M Henry1, A Meyerhans2 and S Wain-Hobson1
Combining the two studies the fraction of HIV RNA that gets converted into a provirus could be as low as 1:100. Hence, as a splenocyte may harbour 3–4 proviruses in vivo, this means that the cell was originally infected by ~300–400 virions. The high ratio and wide range in the number of virions making it to the provirus indicates a substantial stochastic component to the infection process.
147 COMPARISON OF EX VIVO HIV-1 FITNESS TO GENETIC DIVERSITY DURING DISEASE PROGRESSION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 147)
RM Troyer1, KR Collins1, A Abraha1, G Vanham2, DM Moore1, E Fraundorf1, K Demers1 and EJ Arts1
These data provide the first in vivo evidence that increases in HIV-1 fitness may be related to increasing viral load and quasispecies diversity.
148 PHENOTYPIC EVOLUTION OF ATTENUATED,DUAL TROPIC HIV-1, HARBOURED BY THE COMMON DONOR OF THE SYDNEY BLOOD BANK COHORT OF LONG TERM SURVIVORS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 148)
PR Gorry, D McPhee, C Chatfield, J Sterjovski, S Wesselingh, J Learmont, S Crowe, B Brew and M Churchill
The Sydney Blood Bank Cohort of long-term survivors consists of a donor and multiple recipients infected with a common, attenuated HIV-1 strain. Viral attenuation has been attributed to a shared deletion in the nef/LTR region.
149 DYNAMICS OF SUPPRESSION OF CXCR4 SPECIFIC HIV-1 STRAINS BY ANTIVIRAL THERAPY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 149)
S Philpott1, H Burger1,2, C Kitchen3, K Anastos4, E Salzer4, D Fish2, N Dunn2, E Robison4, C Brunner1 and B Weiser1,2
A shift in HIV-1 coreceptor usage also occurred in viruses derived from the female genital tract, but the dynamics of decline differed somewhat from that observed in plasma. Shifts in HIV-1 coreceptor usage occur rapidly following initiation of HAART. The biphasic character of decline may reflect different kinetics related to coreceptor utilization by HIV-1.
150 THE M184V MUTATION IN HIV-1 REVERSE TRANSCRIPTASE (RT) COMPROMISES THE INITIATION OF REVERSE TRANSCRIPTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 150)
M Wainberg1,3, X Wei1,2, K Diallo1,2 and M Gotte1,3
These findings provide: 1. evidence that initiation of tRNALys3-primed DNA synthesis is rate-limiting in reverse transcription and impacts on viral replication fitness; 2. provides biochemical understanding for the reduced replicative capacity of M184V-containing viruses.
151 CD4+ T-CELL SURFACE CCR5 DENSITY IS A PREDICTIVE FACTOR OF HIV REBOUND AFTER ANTIRETROVIRAL TREATMENT INTERRUPTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 151)
P Portales1, V Baillat2, C Merle de Boever2, V Lemoing2, J Clot1, J Reynes2 and P Corbeau1,3
We observed a strong logarithmic correlation (r=0.709, P<0.001) between CCR5 expression and HIV-1 RNA plasma level at day 30. Interestingly, beyond a threshold of 8,000 CCR5 molecules per CD4+ T cell, virus load rebounded above 100,000 copies/ml. These results emphasize the role of CCR5 density in in vivo HIV-1 replication. Moreover, they point out CCR5 density as a predictive factor of the effect of treatment interruption, which should be reserved for patients expressing low CCR5 densities.
152 INDEPENDENT EVOLUTION AND COMPARTMENTALIZATION OF HIV-1 BETWEEN BLOOD MONOCYTES AND CD4+ T-CELLS IN THE PRESENCE OR ABSENCE OF ANTIRETROVIRAL THERAPY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 152)
T Zhu, Y Hwangbo, JA Fulcher, L Heath, D Nickle, R Zioni, J Mullins and L Corey
We have demonstrated that HIV-1 replicates in CD14+ monocytes in vivo, and that monocytes could be an important source of virus in patients with highly active antiretroviral therapy (HAART).
153 THE IMPACT OF NON-B CLADE HIV-1 INFECTION ON ANTIRETROVIRAL DRUG SUSCEPTIBILITY IN NORTH AND SOUTH AMERICA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 153)
C Vavro, A Florance and M St Clair
While the impact of this shift in genetic diversity was not associated with the antiretroviral susceptibility to NRTIs, the presence of reduced phenotypic susceptibility and absence of known NNRTI mutations may suggest an alternative pathway of resistance for NVP.
| July 2003 | Tuesday 15th . 14:30-16:30
Session 30OA - Oral Abstract
Microbicides/Voluntary Counselling and Testing
Chair persons
John N. Nkengasong, Project RETRO-CI, Abidjan, Côte d’Ivoire
Fulvia Veronese, Office of AIDS Research, National Institutes of Health, Bethesda, USA

154 TARGETED INHIBITION OF CCR5 IS SUFFICIENT TO BLOCK MUCOSAL TRANSMISSION OF SHIV: EFFECTS OF TOPICAL PSC-RANTES IN RHESUS MACAQUES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 154)
R Veazey1, C Kirijan1, R Offord2, O Hartley2, D Mosier3, A Blauvelt4 and M Lederman5
Strategies targeting CCR5 are sufficient to block transvaginal infection with SHIV in rhesus macaques. These results have important implications regarding the mechanisms of infection and protection against vaginal transmission of HIV.
155 PROTECTIVE EFFICACY OF CELLULOSE ACETATE PHTALATE (CAP) AGAINST VAGINAL TRANSMISSION OF SIMIAN/HUMAN IMMUNODEFICIENCY VIRUSES IN RHESUS MACAQUES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 155)
T Boadi1, M Ratterree2, A Gettie1, J Blachard2 and C Cheng-Mayer1
Heterosexual transmission accounts for the majority of new human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) infections in the developing world. The formulation of a cheap, safe, effective and practical preventive agent is paramount in combating the pandemic.
156 SULFATED ESCHERICHIA COLI K5 POLYSACCHARIDE DERIVATIVES INHIBIT HUMAN IMMUNODEFICIENCY TYPE -1 (HIV-1) INFECTION IN T-CELLS AND MACROPHAGES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 156)
D Pinna1, G Zoppetti2, P Oreste2,G Poli1 and E Vicenzi1
Here we have investigated the potential anti-HIV-1 effects of sulfated E. coli K5 polysaccharide derivatives that have a backbone structure resembling that of the heparin precursor and N-acetyl heparosan, but they are devoid of the heparin anti-coagulant activity
157 CORRELATION BETWEEN THE VIRUCIDAL ACTIVITY OF NNRTIs AND THEIR BINDING MODE TO THE HIV-1 RT
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 157)
C Musiu1, C Chan1, G Maga2, S Spadari2 and P La Colla3
Although progress has been made in post-infection treatment strategies for HIV-infected individuals, development of effective topical microbicides to control sexual HIV transmission has lagged behind.
158 HIGHLY TARGETED USE OF NON-OCCUPATIONAL POST EXPOSURE PROPHYLAXIS (NPEP) IN AUSTRALIA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 158)
A Grulich1, W Zheng1, S Kippax2 and DE Smith1
This study demonstrates in the setting of a concentrated HIV epidemic, highly targeted prescribing for NPEP is feasible. The lack of identified cases of HIV infection among 819 potential exposures suggests that NPEP may be an effective preventive intervention against HIV, but loss to follow-up precludes a definitive conclusion.
159 PREDICTORS OF ENROLLMENT AND RETENTION FOR HIV DISCORDANT COUPLES IN LUSAKA, ZAMBIA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 159)
MC Kempf1 and the Rwanda/Zambia HIV Research Group 1-3
Enrollment and retention of discordant couples is a challenge, particularly in couples with HIV+ women. Clinical trials will need to plan for high attrition rates, whereas observational studies should reference potential biases in retention.
160 AN ASSESSMENT OF PLANS AND OPTIONS TAKEN BY CLIENTS WHO RECEIVE VOLUNTARY COUNSELLING AND TESTING SERVICES AT AIDS INFORMATION CENTRE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 160)
E Murana, D Kajungu and E Tumuhairwe
Voluntary counseling and testing appeared to influence client’s decisions on options to take for both positive (abstinence, disclosure, nutrition) and negative clients (faithfulness, retesting and testing partners). Interestingly there is little difference on opting for condom use.
161 DETERMINANTS OF THE USE OF VOLUNTARY COUNSELLING AND TESTING SERVICES AMONG THE SEXUALLY ACTIVE ADULT POPULATION OF SOUTH AFRICA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 161)
L Simbayi, O Shisana, J Chauveau and S Ramlagan
These findings, especially those regarding the possible role of both self-efficacy and proximity to HIV/AIDS in the use of VCT services, have serious implications for HIV/AIDS prevention in general and the effectiveness of VCT services in South Africa in particular.
| July 2003 | Tuesday 15th . 14:30-16:30
Session 31OA - Oral Abstract
Resistance and Pharmacology
Chair persons
Françoise Brun-Vézinet, Hospital Bichat-Claude Bernard, Paris, France
Steven Deeks, University of California, San Francisco, USA

162 COMBINED VIRAL LOAD AND PHENOTYPIC DRUG SUSCEPTIBILITY TESTING ON HIV-1 REVERSE TRANSCRIPTASE (RT) RECOVERED DIRECTLY FROM PLASMA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 162)
A Malmsten1,3, XW Shao2,3, G E Corrigan3, I Pettersson3, JS Gronowitz3 and CFR Källander3
RT derived from virions recovered from plasma of HIV infected individuals can be used for both VL and direct phenotypic drug susceptibility testing. The methods presented provide a combined simple VL and drug suscepibility capability particularly suitable for resource limited settings using therapy based on NNRTI and T analogue drugs.
163 HIV-1 GENOTYPIC RESISTANCE TO ANTIRETROVIRAL TREATMENT IN CAMEROON, IN POPULATIONS TREATED BY HAART AND BY SINGLE-DOSE NEVIRAPINE TO PREVENT MTCT
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 163)
C Kouanfack1, L Vergne2, M Tardy1, N Noumssi1, A Bourgeois2, AF Aghokeng2, M Peeters2 and E Delaporte2
This Cameroonian experience shows that HAART selected numerous mutations conferring high level resistances to three antiretroviral classes, notably cross-resistances involving a limited alternative therapeutic choice. It is necessary to implement antiretroviral therapy guidelines and biological monitoring in Africa to avoid rapid selection of resistance.
164 STABLE PREVALENCE OF GENOTYPIC DRUG RESISTANCE MUTATIONS BUT INCREASE IN NON-B VIRUS AMONG PATIENTS WITH HIV-1 PRIMARY INFECTION IN FRANCE IN 2001–2002, COMPARED TO PREVIOUS YEARS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 164)
ML Chaix1, V Schneider2, C Deveau3, P Palmer4, I Pellegrin5, V Brodard6, B Masquelier5, M Harzic7, C Buffet-Janvresse8, C Poggi9, C Rouzioux1, D Costagliola10, F Brun-Vezinet11, L Meyer3 and the ANRS AC11 Resistance Group, Cohort PRIMO, INTERPRIM and PRIMSTOP Study Groups
During 2001–2002, there was no significant evolution of the frequency of resistant virus compared to previous results from 1996–2000. We noted however an increasing trend in the frequency of non-B subtype strains (19% in 1999–2000 vs 24% in 2001–2002).
165 EFFICACY OF RITONAVIR/AMPRENAVIR CONTAINING REGIMEN IN HIV-1 PROTEASE INHIBITOR EXPERIENCED PATIENTS AND PREDICTIVITY OF THE DELTA VIRAL LOAD VALUES UP TO WEEK 24 USING GENOTYPIC INHIBITORY QUOTIENT
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 165)
AG Marcelin1, C Lamotte2, H Ait Mohand3, C Delaugerre1, N Ktorza3, P Bossi3, F Bricaire3, D Costagliola3, C Katlama3, G Peytavin2, and V Calvez1
This study shows a sustained efficacy of r/APV containing regimen in PI experienced patients up to W24 and suggests that GIQ could be used in therapeutic drug monitoring. This approach could help to define plasma concentrations needed to control replication of viruses with different levels of PI resistance measured by the number of PI resistance mutations.
166 WHAT ROLE FOR THE INTRACELLULAR PHARMACOLOGY OF NUCLEOSIDE ANALOGUES?
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 166)
H Benech, A Pruvost and J Grassi
IC monitoring appears to be very efficient in studying drugdrug interactions that interfere with the phosphorylation of nucleosides. In the next few years, we can expect to gain a better understanding of the IC metabolism of NRTIs thus allowing improved monitoring of individual treatments.
167 AMBULATORY EEG AND THERAPEUTIC DRUG MONITORING IN THE MANAGEMENT OF EFAVIRENZ-RELATED INSOMNIA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 167)
P Barreiro1, L Gallego1, R del Río2, D González-Requena1, A Rodríguez-Albariño2, J González-Lahoz1 and V Soriano1
HIV+ patients with EFV-related insomnia show significant sleep architecture abnormalities. Both insomnia and reduced sleep efficiency correlate with EFV plasma levels. EFV sleep complaints may ameliorate after drug dose adjustment.
168 PHOSPHORYLATION OF ANTI-AIDS NUCLEOTIDE ANALOGueS BY NUCLEOSIDE DIPHOSPHATE (NDP) KINASE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 168)
S Gallois-Montrun1, B Schneider1, Y Chen2, S Morera2, J Janin2, D Deville-Bonne1 and M Veron1
After entry in the cell, anti-AIDS nucleoside analogues (ddC, ddI, AZT, d4T, 3TC) are converted into triphosphate by three successive reactions catalyzed by enzymes from the salvage pathway: nucleoside kinases, NMP kinases and NDP kinase. The triphosphate analogues then compete with natural dNTP for incorporation into the viral DNA.
169 COMPARATIVE PHARMACOKINETICS OF HIV-1 NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIs) OF THE DATA AND DAPY CLASSES OF COMPOUNDS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 169)
P Lewi1, K Andries3, E Arnold4, H Bohets2, A Clark4, F Daeyaert1, K Das4, MP de Béthune3, M de Jonge1, J Heeres1, PAJ Janssen1, L Koymans1, J Peeters2, P Timmerman2, G Van’t Klooster3, M Vinkers1 and Y Volovik4
A large number of NNRTIs belonging to the classes of diaryl-triazine (DATA) and diaryl-pyrimidine (DAPY) analogues has been synthesized during the last 9 years. During this period a vast amount of physicochemical, virological, preclinical and clinical data has been obtained, including metabolic and pharmacokinetic results from various animal species and man.
| July 2003 | Tuesday 15th . 14:30-16:30
Session 32OA - Oral Abstract
HIV Pathogenesis
Chair persons
Mario Clerici, Milan University Medical School, Italy
Hiroaki Mitsuya, Kumamoto University School of Medicine, Japan

170 CORRELATION BETWEEN T-CELL TURNOVER AND DISEASE PROGRESSION IN SIV-INFECTED MACAQUES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 170)
S Sopper1, C Scheller1, C Stahl-Hennig2, J Müller3 and V ter Meulen1
Loss of CD4+ T-cells from blood is a well-known hallmark of HIVinfection. It is common thought that this translates into decreased numbers of CD4+ T-cells throughout the body. However, quantitative analyses about HIV-induced changes of T-cell numbers in the organs are lacking.
171 EFFECTS OF DIFFERENT STAGES OF HIV-1 DISEASE ON THYMIC ACTIVITY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 171)
R Correa1–2, M Nobile1, K Ellefsen-Lavoie1, E Aschwanden1, M Spasojevic1, C D’Agostino1, L Codarri1, P Lieby1, R Chawla1, M Khonkarly1 and G Pantaleo1
These data suggest that HIV-infected subjects with CD4 cell counts >200 show normal or increased thymic activity within CD4 T cells, whereas the lower TREC levels observed within CD8 T cells could be due to a dilution effect caused by an increased as division rate as supported by the negative correlation with Ki67. The increased division in CD8 T cells may be mediated by the increase in IL-7 plasma levels.
172 R5 HIV-1 INFECTION OF FOETAL THYMIC ORGAN CULTURE INDUCES CYTOKINE AND CCR5 EXPRESSION: COMPONENTS OF A PATHOGENIC PATHWAY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 172)
S Choudhary1, K Kimbrell1, J Colasanti1, D Chernauskas1, D Kwa2, H Schuitemaker2 and D Camerini1
CCR5 tropic HIV-1 isolates (R5 HIV-1) predominate following transmission, during the clinically latent period and are the only type of HIV-1 ever found in approximately half of AIDS patients. Nevertheless, the pathogenesis of R5 HIV-1 is not well understood since few thymocytes or T cells express CCR5. Involvement of the thymus is a common and detrimental component of HIV-1 infection.
173 EXPANSION OF CD4+CD25+ REGULATORY T-CELLS WHICH SUPPRESS HIV-SPECIFIC CD4 T-CELL RESPONSES IN HIV-INFECTED PATIENTS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 173)
L Weiss1, V Donkova-Petrini1, L Caccavelli1, C Carbonneil1 and Y Levy2
CD4+CD25+ T cells in HIV-infected pts exhibited characteristics of regulatory T cells and suppressed the proliferative responses of CD4 T cells to recall antigens and to p24 protein. Expansion of these regulatory T cells may participate to immune deficiency in HIV infection.
174 CD4+CD25+ T-CELLS SUPPRESS HIV-SPECIFIC IMMUNE RESPONSES AND CD8+ CELL-MEDIATED INHIBITION OF HIV REPLICATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 174)
A Kinter, S Kern, Y Lin, M Hennessey, M Daucher, R Jackson and AS Fauci
CD4+CD25+ regulatory T cells (Treg) isolated from the peripheral blood of HIV(–) healthy donors have been demonstrated to inhibit CD4+ and CD8+ immune responses both in vitro and in vivo. To date, the effect of CD4+CD25+ Treg cells in the context of HIV disease has not been investigated.
175 IMMUNODEFICIENCY INTERNALIZATION BY DENDRITIC CELLS AND TRANSFER TO CD4 LYMPHOCYTES OCCURS IN TWO DISTINCT PHASES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 175)
SG Turville1, JJ Santos2, I Frank2, PU Cameron3, J Wilkinson1, M Miranda-Saksena1, J Dable1, H Stössel4, N Romani4, M Piatak5, JD Lifson5, M Pope2 and AL Cunningham1
Herein we observe DC transfer HIV in two distinct phases, the first short term phase zidovudine insensitive and visualized by endocytotic trafficking to the DC-T-cell synapse and the second long term phase zidoviduine sensitive and therefore by de novo HIV production within MDDCs.
176 VARIATIONS IN CIRCULATING AND SPLEEN IMMUNE CELLS START 24 HOURS AFTER RECTAL SIV INFECTION IN RHESUS MONKEYS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 176)
C Butor1,2, K Petitprez1, S Kahi1, A Couëdel-Courteille1,2, S Jacques1, M Andrieu1, P Lebon3, JL Prétet1,4 and A Hosmalin1
This is the first time immune responses are studied starting 24 hours pi in primates. The selective changes in circulating DC subsets and CD56+/CD3– lymphocytes strongly suggest a specific role for these cells in setting the balance between the innate and adaptive immune responses and viral replication.
177 T-CELLS THAT HARBOUR HIV IN VIVO: IMPLICATIONS FOR PATHOGENESIS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 177)
D Douek, B Hill, D Ambrozak, D Price, J Casazza, J Kurupuu, M Connors, M Roederer, R Koup and J Brenchley
HIV primarily infects activated memory CD4+ T-cells in vitro, however, other subsets of cells within the myeloid and lymphoid lineages are also capable of becoming infected by HIV if they express CD4 together with an appropriate chemokine coreceptor. A clear appreciation of precisely which cells are infected during the course of HIV disease is essential to an understanding of HIV pathogenesis, but determining which cells are infected in vivo has remained technically difficult.
| July 2003 | Tuesday 15th . 14:30-16:30
Session 33OA - Oral Abstract
HIV Vaccines
Chair persons
Michel Klein, CANVAC, University of Montreal, Canada
Tomas Hanke, Weatherall Institute of Molecular Medicine, Oxford University, UK

178 ATTENUATION OF SIVMAC239 AND SHIV89.6P INFECTIONS BY REPLICATION-DEFECTIVE ADENOVIRUS VACCINES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 178)
JW Shiver1, DR Casimiro1, X Liang1, WA Schleif1, F Wang1, Z Zhang1, A Bett1, M Davies1, LG Tussey1, JH Condra1, T Fu1, L Handt1, AB McDermott2, DI Watkins2 and EA Emini1
We compared nonreplicating adenovirus type 5 (Ad5) and DNA/Ad5 immunization against SIVmac239 and SHIV89.6P challenges. For the SIV challenge MHC Class I allele MamuA*01+ and MamuA*01-monkeys were immunized with Ad5-SIV gag, alone or as an SIV gag DNA prime/Ad5-gag boost combination.
179 MEASLES VACCINE AS A POTENTIAL VECTOR FOR AIDS VACCINATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 179)
F Tangy1, C Combredet1, V Labrousse1, C Lorin1, L Mollet1, M Brahic1 and B Hurtrel2
Live attenuated measles vaccine (MV) has an excellent record of safety and efficacy. A single low-dose injection induces a life-long protective immunity. Efficient long-lasting humoral and cellular immune responses mediate protection. MV vaccine is easy to produce, cheap and the logistic to deliver it worldwide is already in place.
180 EFFICACY OF DNA AND FOWLPOXVIRUS PRIME/BOOST VACCINES FOR HIV-1 AND SHIV
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 180)
SJ Kent1, CJ Dale1, R De Rose1, I Stratov1, S Chea1, DFJ Purcell1, IA Ramshaw2, S Thomson2, DB Boyle3, B Coupar3, AJ Ramsay4, R Ffrench5, M Law5, S Emery5 and DA Cooper5 for the Australian HIV Vaccine Design and Development Team
An optimised set of DNA and FPV HIV-1 vaccines, suitable for proceeding into human clinical trials, are highly immunogenic and protective in macaques.
181 Th1 PLASMID CYTOKINE ENHANCEMENT OF RNA OPTIMIZED PLASMID DNA VACCINE POTENCY IN NON-HUMAN PRIMATES SUGGESTS ATTAINMENT OF A CRITICAL MILESTONE IN DNA VACCINE AND IMMUNE THERAPY DEVELOPMENT
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 181)
DB Weiner1, J Boyer1, M Kutzler1, RR MacGregor1, T Robinson1, A Choo1, M Chattergoon1, K Muthumani1, S Calarota1, M Otero1, M Lewis4 ,N Letvin5, EB Schadeck2, M Sidhu2, MA Egan2, G Pavlakis3, Z Israel2 and J Eldridge2
Over the past 13 years DNA vaccines have moved from a laboratory curiosity to an important immunization approach. We have recently observed in a therapy study in the context of HAART that these vaccines induce CD8 T cell responses and result in lower viral loads in humans. However, the quality and longevity of the responses induced even with highly optimized plasmid cassettes is still significantly below that of vector live approaches.
182 HIV-1 VACCINES THAT INCLUDE NOVEL ENVELOPE STRUCTURES INDUCE BROAD AND POTENT ANTI-VIRAL IMMUNE RESPONSES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 182)
SW Barnett1, I Srivastava1, L Stamatatos2, J Zur Megede1, G Otten1, D Montefiori3, S Engelbrecht4, E Janse van Rensburg4, D O’Hagan1, J Polo1, J Ulmer1 and J Donnelly1
Improved antigenic structures and enhanced deliveries will be essential components of HIV vaccines for future clinical evaluations.
183 LENTIVIRAL VECTORS AS POTENTIAL TOOLS FOR DENDRITIC CELL-MEDIATED THERAPEUTIC VACCINATION AGAINST AIDS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 183)
C Iglesias1, L Mollet2, K Courbeyrette1, F Tangy2, P Langlade-Demoyen3, F Lemonnier3 and P Charneau1
The relative vaccination efficiency of stably-transduced DCs versus pulsed-DCs will be directly examined. The diversity of the response and the establishment of a memory immunity will be also compared.
184 MODELLING IMMUNE INTERVENTION STRATEGIES FOR HIV-1 INFECTION OF HUMANS IN THE MACAQUE MODEL
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 184)
G Franchini
The introduction of ART has resulted in effective suppression of viral replication and decreased morbidity and mortality of HIV-1-infected individuals. The decreased morbidity appears to be associated with the reconstitution of immune responses to pathogens, such as cytomegalovirus and Epstein–Barr virus
185 HIV-RECOMBINANT CANARYPOX VACCINE BOOSTS AND BROADENS HIV-SPECIFIC CD4 AND CD8 T-CELLS IN THE VACCITER ANRS094 THERAPEUTIC IMMUNISATION CLINICAL TRIAL
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 185)
G Carcelain1, R Tubiana2, M Legarff1, C Dalban3, C Rabian4, V Calvez5, R Elhabib6, C Katlama2 and B Autran1 for the Vacciter Study Group
This first immunogenicity study in chronic HIV infection shows HIV-recombinant-vCP can significantly boost and broaden HIV-specific CD4 and CD8 T cells and help delay therapy. Immunogenicity could still be improved with new schedules of administration in future trials.
| July 2003 | Tuesday 15th . 14:30-16:30
Session 34OA - Oral Abstract
HIV Replication and Viral Regulatory Proteins
Chair persons
Pierre Charneau, Institut Pasteur, Paris, France
Michael Bukrinsky, George Washington University Medical Center, Washington, USA

186 ROLE OF hSNF5/Ini1 IN HIV-1 INTEGRATION AND REPLICATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 186)
M Maroun1, C Petit1, P Sonigo1, M Benkirane2, R Benarous1 and S Emiliani1M Maroun1, C Petit1, P Sonigo1, M Benkirane2, R Benarous1 and S Emiliani1
We are currently investigating at which level of the viral replication cycle hSNF5/Ini1 plays its role. These preliminary results suggest that hSNF5/Ini1 could be involve in an anti-viral cellular response.
187 INI1 SILENCING BY LENTIVIRAL-MEDIATED SIRNA DELIVERY LEADS TO RESTRICTION OF HIV-1 INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 187)
J Thomas, M Muñoz, C Loeuillet, A Ciuffi and A Telenti
Silencing of INI1 confirms its role in sustaining viral replication. The decrease in replication may reflect a delay of the integration/proviral expression phase. However, we failed to identify a clear role of INI1 in the viral life cycle through modification of cell division, or in viral particle maturation. Splicingspecific silencing may help understand the differential role of isoforms in HIV pathogenesis.
188 LUMAN, A CYCLIC AMP RESPONSE ELEMENT (CRE)-BINDING PROTEIN/ACTIVATING TRANSCRIPTION FACTOR, A NEW PARTNER OF THE CYTOPLASMIC DOMAIN OF HIV-1 TMgp41
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 188)
G Blot, S Lopez, R Benarous and C Berlioz-Torrent
The HIV-1 transmembrane envelope glycoprotein (TMgp41) contains an unusually long intracytoplasmic domain. The TMgp41 intracytoplasmic domain plays a role in the envelope fusogenicity, the trafficking of envelope into the cell, its incorporation during viral assembly and consequently in the viral infectivity.
189 A JANUS SPLICING REGULATORY ELEMENT MODULATES HIV-1 TAT AND REV mRNA PRODUCTION BY COORDINATION OF hnRNP A1 COOPERATIVE BINDING
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 189)
V Marchand1, A Méreau1, S Jacquenet1, D Thomas1, A Mougin1, R Gattoni2, J Stévenin2 and C Branlant1
Retroviral protein production depends upon alternative splicing of the viral transcript. The HIV-1 acceptor site A7 is required for tat and rev mRNA production. Production of the Tat transcriptional activator is highly controlled because of its apoptotic properties.
190 GAGPOL DOMAINS RESPONSIBLE FOR THE LOCALIZATION OF GAG/GAGPOL COMPLEX TO DRM MUCH FASTER THAN GAG/GAG COMPLEXES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 190)
R Halwani1,2, MA Wainberg1,3 and L Kleiman1,3
The purpose of this work is to study the movement of Gag/GagPol complex to the different membrane fractions during HIV-1 assembly, and to determine the Pol domains responsible of such movement.
191 ERK-2 DEPENDENT PHOSPHORYLATION OF P6GAG PROTEIN IS REQUIRED FOR HIV-1 REPLICATIVE CYCLE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 191)
B Hemonnot, C Cartier, B Gay, M Bardy, C Devaux and L Briant
Biochemical analysis of Gag processing and electron microscopy revealed that the mutants virions contained maturation intermediate products and displayed immature morphology. Altogether, our data indicate that p6gag phosphorylation would be required for HIV-1 assembly and/or maturation.
192 HIV-1 NEF ASSOCIATES WITH LIPID RAFTS TO DOWN-MODULATE CELL SURFACE CD4 AND CLASS I MHC EXPRESSION AND TO INCREASE VIRAL INFECTIVITY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 192)
D Rekosh, M Alexander, K Ravichandran, ML Hammarskjold and H Myles
Lipid rafts are membrane microdomains that are functionally distinct. We have shown that 10% of HIV Nef expressed in SupT1 cells is present in lipid rafts and that this represents virtually all of the membrane-associated Nef.
193 HIV-1 VPU INTERFERES WITH NFkB AND CATENIN SIGNALING PATHWAYS BY ACTING AS A GENERAL COMPETITOR OF THE SCFTRCP E3 LIGASE SUBSTRATES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 193)
C Besnard-Guerin, N Belaidouni, I Lassot, A Jobart, R Benarous
HIV-1Vpu acts as an adapter for proteasome targeting of CD4 by recruting CD4 and βrCP, a component of the ubiquitin ligase complexe. The βrCP protein is also involved in targeting several cellular proteins including β catenin, IBα and ATF4 to ubiquination and degradation by the proteasome.
| July 2003 | Tuesday 15th . 17:00-18:00
Session 35OA - Oral Abstract
There Is More Risk than Value in Treatment Interruptions
Moderator
Gregg Gonsalves, Gay Men’s Health Crisis (GMHC), New York, USA
194* PRO SPEAKER
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 194)
Diane V. Havlir, University of California, San Francisco, USA
Abstract not available
195* CON SPEAKER
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 195)
Bernard Hirschel, Geneva University Hospital, Switzerland
Abstract not available
| July 2003 | Tuesday 15th . 17:00-18:00
Session 36OA - Oral Abstract
The Use of Single-Dose versus Combination Therapy to Prevent Mother-to-Child Transmission?
Moderator
Chewe Luo, UNICEF, Nairobi, Kenya
196* PRO SPEAKER
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 196)
John Sullivan, University of Massachusetts Medical School, Worcester, USA
Abstract not available
197* CON SPEAKER
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 197)
François Dabis, University of Bordeaux, France
Abstract not available
| July 2003 | Tuesday 15th . 17:00-18:00
Session 37OA - Oral Abstract
Treatment for HIV Should be Based on Results of Clinical Trials More than on Viral Pathogenesis
Moderator
François Raffi, University Hospital Hôtel-Dieu, Nantes, France
198* PRO SPEAKER
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 198)
Scott Hammer, Columbia University College of Physicians and Surgeons, New York, USA
Abstract not available
199* CON SPEAKER
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 199)
Brian Gazzard, Chelsea and Westminster Hospital, London, UK
Abstract not available
| July 2003 | Tuesday 15th . 17:00-18:00
Session 38OA - Oral Abstract
Can a Vaccine that Induces T-Cell Responses Control HIV ?
Moderator
Simon Wain-Hobson, Institut Pasteur, Paris, France
200* PRO SPEAKER
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 200)
Richard A. Koup, NIAID Vaccine Research Center, NIH, Bethesda, USA
Abstract not available
201* CON SPEAKER
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 201)
Ruth M. Ruprecht, Harvard Medical School, Boston, USA
Abstract not available
| July 2003 | Wednesday 16th . 8:30-9:30
Session 39PL - Plenary
Chair persons
Jean-François Delfraissy, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France
Douglas D. Richman, University of California, San Diego, USA
202* HIV ENTRY: INSIGHTS INTO VIRAL TROPISM, PATHOGENESIS, AND ANTIVIRAL THERAPY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 200)
Robert Doms, University of Pennsylvania, Philadelphia, USA
Abstract not available
203* MECHANISMS AND MANAGEMENT OF METABOLIC COMPLICATIONS ASSOCIATED WITH HIGHLY ACTIVE ANTIRETROVIRAL THERAPY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 201)
Peter Reiss, Academic Medical Center, University of Amsterdam, The Netherlands
Abstract not available
| July 2003 | Wednesday 16th . 10:00-12:00
Session 40FO - FORUM
MECHANISMS OF ANTIRETROVIRAL TOXICITIES
Conveners
Jacqueline Capeau, Faculty of Medicine, Saint-Antoine and Tenon Hospitals, Pierre et Marie Curie University, Paris, France
Morris Schambelan, University of California, San Francisco, USA

204* STATE-OF-THE-ART TALK: PATHOPHYSIOLOGY OF METABOLIC TOXICITIES: INSIGHTS FROM BASIC RESEARCH
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 204
Jacqueline Capeau, Faculty of Medicine, Saint-Antoine and Tenon Hospitals, Pierre et Marie Curie University, Paris, France
Abstract not available.
205* STATE-OF-THE-ART TALK: PATHOPHYSIOLOGY AND TREATMENT OF METABOLIC TOXICITIES: INSIGHTS FROM CLINICAL RESEARCH
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 205
Morris Schambelan, University of California, San Francisco, USA
Abstract not available.
206 EFFECTS OF NRTI ON DIFFERENTIATION, RESPONSE TO INSULIN AND APOPTOSIS IN CULTURED ADIPOCYTES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 206
M Caron, M Auclair, M Kornprobst and J Capeau
Three of the NRTIs tested (ABC, ddI and 3TC) did not modify adipose cell functions while d4T and ZDV decreased cell lipid content and mildly increased apoptosis. ZDV also induced insulin resistance. These results indicated that the thymidine analogues d4T and ZDV but not the other NRTIs presented some adverse effects in cultured adipocytes.
207 REGULATION OF RANKL EXPRESSION BY HIV ENVELOPE gp120 AND ITS MODULATION BY HIV PROTEASE INHIBITORS THROUGH INTERFERON-γRANKL CROSS TALK
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 207
MF Jamiluddin and J Laurence
These findings offer a molecular basis for the acceleration of bone demineralization by certain PIs, and provide the first example of clinically useful drugs which can interfere with cross-talk between RANKL and interferon-γ via the proteasome. They also suggest a novel therapeutic approach to HIV osteopenia, through modulation of these two signals.
208 ANTIRETROVIRAL THERAPY WITH DDI, D4T OR DDC IS ASSOCIATED WITH DEPLETION OF MITOCHONDRIAL DNA IN LIVER
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 208
UA Walker1, J Bäuerle1, M Laguno2, J Murillas2, S Mauss3, G Schmutz3, B Setzer1, R Miguel2, JM Gatell2 and J Mallolas2
Current treatment with DDI, D4T, or DDC is associated with decreased mtDNA in liver irrespective of liver cirrhosis and inflammatory activity. This may be an important (but not exclusive) factor contributing to hyperlactataemia.
209 ASSESSMENT OF SMALL PERIPHERAL NERVE FIBRES ALTERATIONS IN HIV-INFECTED PATIENTS EXHIBITING LIPODYSTROPHY SYMPTOMS AFTER LONG-TERM EXPOSURE TO NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIs)
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 209
B Jarrousse1, S Bouillaguet2–4, PH Letoumelin3, P Honoré1, PA Klutse1, N Danziger4 and JC Willer4
Patients durably exposed to NRTIs revealed a loss of responsiveness of capsaicin-sensitive nociceptors, suggestive of alterations in small peripheral nerve fibres that may be linked to mitochondrial toxicity.
| July 2003 | Wednesday 16th . 10:00-12:00
Session 41FO - FORUM
Co-Infection with Hepatitis Viruses
Conveners
Marion Peters, University of California, San Francisco, USA
Jürgen Rockstroh, University of Bonn, Germany

210* MANAGEMENT OF HEPATITIS C IN HIV CO-INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 210)
Jürgen Rockstroh, University of Bonn, Germany
Abstract not available
211* UPDATE ON HIV/HBV CO-INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 211)
Marion Peters, University of California, San Francisco, USA
Abstract not available
212 EARLY HCV KINETICS PREDICTS RESPONSE TO PEG-INTERFERON-ALPHA 2B AND RIBAVIRIN ANTI-HCV THERAPY AMONG HIV CO-INFECTED INDIVIDUALS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 212)
S Kottilil1, M McLaughlin1, I Sidorov4, B Hahn2, C Ternisky1, C Koratich1, K Shin1, J Kovacs2, J Tavel1, R Davey1, H Masur2, J Metcalf1, TJ Liang3, D Dimitrov4 and MA Polis1
Peg-IFN+RBV therapy is associated with 50% ETR in a HIV/HCV co-infected cohort despite poor baseline prognostic characteristics (genotype 1, African-American origin, high baseline HCV viral load). Preliminary analyses indicate that Day0–10 HCV kinetic response may predict EVR and ETR among co-infected individuals. Co-infected individuals may have a slower response to standard therapy as suggested by the ETR among persons with delayed initial responses to therapy.
213 DOES HCV CO-INFECTION INCREASE THE INCIDENCE OF NON-ALCOHOLIC CIRRHOSIS AND HEPATOCELLULAR CARCINOMA? A COHORT STUDY OF HIV-INFECTED US VETERANS, 1992-2001
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 213)
TP Giordano1,2, JR Kramer3, J Souchek1,2, PA Richardson2 and HB El-Serag1,2
These are the first observational data on the incidence of HCC in HIV. HCV co-infection dramatically promotes the development of HCC (6-fold) and NAC (10-20 fold), and is especially associated with NAC in the HAART era. Treatment of HCV should be considered.
214 THE IMPACT OF THE HEPATITIS C VIRUS (HCV) ON CD4 RESPONSE POST INITIATION OF HAART AMONG A POPULATION-BASED HIV TREATMENT COHORT
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 214)
P Braitstein1,2, JJ Asselin1, V Montessori1, E Wood1,2, B Yip1, K Chan1, KJP Craib1,2, MV O'Shaughnessy1,3, MT Schechter1,2, JSG Montaner1,2 and RS Hogg1,3
There appears to be an altered CD4 response over time among HCV-positive individuals following initiation of HAART, even after controlling for adherence. The clinical significance of these differences remains to be determined.
215 Anti-HBV Activity of Emtricitabine (FTC) in Patients Co-Infected with HIV and Hepatitis B Virus
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 215)
F. Raffi1, A.Snow2, K. Borroto-Esoda2, A. Shaw2, J. Anderson2, J. Sorbel2, J. Quinn2, E. Mondou2, F. Rousseau2
FTC as a component of HAART produced potent suppression of HBV DNA in co-infected patients with HIV RNA suppression.
| July 2003 | Wednesday 16th . 10:00-12:00
Session 42FO - FORUM
Mother-to-Child HIV Transmission
Conveners
Ruth Nduati, University of Nairobi, Kenya
Glenda Gray, University of the Witwatersrand, Johannesburg, South Africa

216* STATE-OF-THE-ART TALK: EFFICACY OF SHORT-COURSE ANTIRETROVIRAL REGIMENS IN BREASTFEEDING POPULATIONS: NARROWING THE GAP
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 216)
Ruth Nduati, University of Nairobi, Kenya
Abstract not available
217* STATE-OF-THE-ART TALK: BEYOND NEVIRAPIN
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 217)
Glenda Gray, University of the Witwatersrand, Johannesburg, South Africa
Abstract not available
218 HYPERLACTATAEMIA IN NEONATES EXPOSED PERIPARTUM TO A SHORT COURSE OF ANTIRETROVIRALS TO PREVENT MOTHER-TOCHILD TRANSMISSION OF HIV (PMTCT): THE ANRS 1209 STUDY. ABIDJAN, CÔTE D’IVOIRE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 218)
DK Ekouévi1,2, F Rouet3, L Bequet1, R Touré3, I Viho1, B Towne-Gold1, G Bédikou1, V Leroy2 and F Dabis2
This study shows that hyperlactataemia can be found in infants whose mother received short-course ARVs for PMTCT. The incidence of hyperlactataemia in this context was lower than what has been reported in the literature. There is no need at this stage to revise the PMTCT recommendations for resource-poor settings based on these findings.
219 EFFECTIVENESS OF A SHORT COURSE OF ZIDOVUDINE + LAMIVUDINE AND PERIPARTUM NEVIRAPINE TO PREVENT HIV-1 MOTHER-TO-CHILD TRANSMISSION. THE ANRS 1201 DITRAME-PLUS TRIAL, ABIDJAN, CÔTE D'IVOIRE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 219)
F Dabis1, DK Ekouevi1,2, F Rouet3, L Bequet2, I Viho2, A Horo4, P Fassinou5, H Toure2, C Welfens-Ekra4, V Leroy2 for the ANRS Ditrame Plus Study Group
This preliminary analysis shows that the combination of ZDV+LAM+NVP prevents most peripartum transmission of HIV in Africa. Enrolment is ongoing to confirm efficacy and document safety.
220 FORMULA FEEDING IS SAFE IN A RESOURCE POOR URBAN SETTING WITH POTABLE WATER
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 220)
D Coetzee1, K Hilderbrand1,3, and E Goemaere2
Formula feeding is safe and feasible in an urban environment where sufficient potable water is available.
221 MORTALITY AMONG HIV-INFECTED MOTHERS AND CHILDREN’S FEEDING MODALITY: THE BREASTFEEDING AND HIV INTERNATIONAL TRANSMISSION STUDY (BHITS)
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 221)
ML Newell, J Read, V Leroy, and F Dabis
Women with more advanced HIV disease, manifested by lower CD4+ around time of delivery, were at increased risk of mortality 12–18 months after delivery. Mothers who ever breastfed were at lower risk of mortality through 12 months after delivery. Ongoing analyses are further assessing the risk of mortality among HIV-infected mothers who ever breastfed.
| July 2003 | Wednesday 16th . 10:00-12:00
Session 43FO - FORUM
New Insights into Non-Human Primate Viruses
Conveners
Jonathan Heeney, Biomedical Primate Research Center, Rijswijk, The Netherlands
Chris Miller, California National Primate Research Center, University of California, Davis, USA

222* STATE-OF-THE-ART TALK: TRANSMISSION OF SIV CPZ IN THE PRESENCE OR ABSENCE OF CONCURRENT HIV-1 INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 222)
Jonathan Heeney, Biomedical Primate Research Center, Rijswijk, The Netherlands
Abstract not available
223* STATE-OF-THE-ART TALK: INNATE AND ADAPTIVE IMMUNE MECHANISMS PROTECTING SHIV-INFECTED RHESUS MONKEYS FROM INTRAVAGINAL SIV CHALLENGE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 223)
Chris Miller, California National Primate Research Center, University of California, Davis, USA
Abstract not available
224 IDENTIFICATION AND MOLECULAR CHARACTERIZATION OF A NEW PRIMATE LENTIVIRUS (SIV ERY) FROM CERCOPITHECUS ERYTHROTIS TISSUE SAMPLES FROM BIOKO, EQUATORIAL GUINEA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 224)
P Reed1,2, S Souquière2, M Makuwa2, P Telfer1,2, MA Ela-Mba3, P Roques2 and P Marx1
These findings reveal the first lentivirus identified in C. erythrotis, which we propose to name SIVery. This is the first SIV originating from the island of Bioko. Sequence analysis and serological testing suggest that SIVery may be a chimeric virus as it groups with SIVgsn in pol region and has an env region profile similar to SIVcpz. These findings may shed light on the origin of HIV-1/SIVcpz. Keywords: Equatorial Guinea, Bioko, Fernando Po, SIVgsn, Cercopithecus erythrotis
225 IDENTIFICATION OF A NEW SIV LINEAGE WITH A VPU GENE PRESENT IN THREE DIFFERENT CERCOPITHECUS MONKEYS FROM CAMEROON
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 225)
V Courgnaud1, S Loul1, E Mpoudi-Ngole2, F Liegeois1, B Abela2, X Pourrut1, E Delaporte1, B Hahn and M Peeters1
This study presents evidence that different evolutionary groups of Cercopithecus monkeys in Cameroon are infected with the same SIV lineage. The origin of vpu has not been yet elucidated but the identification of additional viruses from monkeys belonging to the Cercopithecus genus having also a vpu homologue could suggest that vpu has been acquired during evolution of an ancestral SIV from Cercopithecus species. Furthermore, the predatory behaviour of chimpanzees and the presence of new viruses closely related to SIVgsn in two other species reinforce the possible hypothesis that a recombination event between ancestral SIVs from the Cercopithecinae family, is at the origin of the current SIVcpz widespread among the chimpanzee population.
226 AIDS AS A ZOONOSIS? CONFUSION OVER THE ORIGIN OF HIV AND THE AIDS EPIDEMIC
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 226)
PA Marx1, C Apetrei1 and E Drucker2
Cross-species transmission of a virus does not in itself constitute the basis of zoonosis, and transmission per se is not the only requirement for the origin of HIVs and the generation of an AIDS epidemic. While all HIVs derive from simian species, AIDS does not qualify as a zoonosis, and this explanation cannot in itself account for the origin of AIDS.
227 IMPORTANCE OF THE THYMIC OUTPUT IN THE PATHOGENESIS OF A LONG-TERM INFECTION BY AN ATTENUATED SIMIAN IMMUNODEFICIENCY VIRUS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 227)
R Ho Tsong Fang1, E Khatissian1, V Monceaux1, MC Cumont1, S Beq1, N Israel1, JC Ameisen2, J Estaquier1 and B Hurtrel1
Absence of SIV detection in the thymus hints that this defect of CD4 thymic output implies an indirect phenomenon. Altogether, our results highlight the role of the thymic output into the CD4 T cell depletion mechanisms.
| July 2003 | Wednesday 16th . 10:00-12:00
Session 44FO - FORUM
Innate Immunity in HIV Infection
Conveners
Jay A. Levy, University of California, San Francisco, USA
Paolo Lusso, San Raffaele Scientific Institute, Milan, Italy

228* STATE-OF-THE-ART TALK: THE IMPORTANCE OF INNATE IMMUNITY IN HIV INFECTION: PLASMACYTOID DENDRITIC CELLS AND CD8+ CELL ANTIVIRAL NONCYTOTOXIC RESPONSES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 228)
Jay A. Levy, University of California, San Francisco, USA
Abstract not available
229* STATE-OF-THE-ART TALK: CHEMOKINES AND CHEMOKINE RECEPTORS: IMPLICATIONS FOR HIV PATHOGENESIS, THERAPY AND VACCINES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 229)
Paolo Lusso, San Raffaele Scientific Institute, Milan, Italy
Abstract not available
230 INDUCIBLE ORAL EPITHELIAL BETA DEFENSINS INHIBIT HIV-1 REPLICATION VIA IRREVERSIBLE VIRION BINDING AND BY CO-RECEPTOR DOWNMODULATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 230)
ME Quiñones-Mateu, MM Lederman, Z Feng, B Chakraborty, J Weber, HR Rangel, ML Marotta, M Mirza, B Jiang, P Kiser, K Medvik and A Weinberg
This work shows for the first time that: (i) HIV-1 induces beta defensin expression in human oral epithelial cells; and (ii) beta defensins block HIV-1 replication via direct binding and inhibition of virion infectivity and through internalization of the CXCR4 coreceptor. These properties may be exploited as new strategies for mucosal protection against HIV-1 transmission.
231 IMPACT OF SDF-1 PRODUCTION BY DENDRITIC CELLS IN HIV INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 231)
M Bermejo1, JL Pablos2, N Gonzalez1, L Sánchez-Verde3, F Baleux4, F Arenzana4 and J Alcami1
These results suggest that the production of SDF-1 by dendritic cells could account for the lack of emergence and low propagation of X4 HIV strains in early and chronic stages of infection.
232 KINETICS OF PERIPHERAL AND TISSUE DENDRITIC CELL SUBSETS DURING THE ACUTE PHASE OF NON-PATHOGENIC SIVAGM INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 232)
OM Diop1, L Mortara2, A Faye1, MJY Ploquin2, C Butor3,4, A Hosmalin3, F Barré-Sinoussi2 and MC Müller-Trutwin2
In blood, we observed an increase in the percentages of both subsets around day 16 pi. In LNs, the kinetics of the two DC subsets were different from each other. At day 42, values observed in both blood and LN returned to levels similar to those before infection. Detailed analysis of DCs subset kinetics in blood and LN will be discussed. This first longitudinal study of peripheral and LN DCs subset variations during primary infection in an animal model for protection against AIDS provide insights into the role of DCs in the early differences described between pathogenic and non-pathogenic lentiviral infections.
233 NK CELL RECEPTOR EXPRESSION ON T CELLS AND NK CELLS DURING HIV INFECTION: CORRELATION WITH THE VIRAL LOAD AND INFLUENCE OF IL-15
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 233)
D Marsac1,3, C Rapp2, P Lanza3, ML Gougeon1 and I Liberman1
We have analysed the expression of (killing inhibitory receptors) KIRs CD94, p158a, p158b and NKB1, in natural killer (NK) cells, CD4+, CD8+ and gamma delta Vγ9 T cells in healthy donors (n=12), asymptomatic HIV-infected untreated patients (n=16) and patients under HAART (n=18).
| July 2003 | Wednesday 16th . 10:00-12:00
Session 45LB - Late Breakers
Late Breakers - Oral
Chair persons
H. Clifford Lane, NIAID, Bethesda, USA
Robin Weiss, Windeyer Institute of Medical Sciences, University College, London, UK

LB1 ANALYSIS FROM MORE THAN 1600 NEWLY DIAGNOSED PATIENTS WITH HIV FROM 17 EUROPEAN COUNTRIES SHOWS THAT 10% OF THE PATIENTS CARRY PRIMARY DRUG RESISTANCE: THE CATCH-STUDY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. LB1)
A.M.J. Wensing1, D.A.M.C. van de Vijver1, B. Asjo2, C. Balotta3, R. Camacho4, A. de Luca5, C. de Mendoza6, S. Deroo7, I. Derdelinckx8, Z. Grossman9, O. Hamouda10, A. Hatzakis11, A. Hoepelman1, A. Horban12, K. Korn13, C. Kuecherer10, T. Leitner14, C. Nielsen15, V. Ormaasen16, L. Perrin17, D. Paraskevis11, E. Puchhammer18, F. Roman7, L. Ruiz19, M. Salminen20, J.C.C. Schmit7, V. Soriano6, G. Stanczak12, M. Stanojevic21, A.M. Vandamme8, K. Van Laethem8, M. Violin3, S. Yerly17, M. Zazzi22, C.A.B. Boucher1, on behalf of the SPREAD Programme
We found a prevalence of primary drug resistance of 10% in Europe. Drug resistance was predominantly found among patients infected with subtype B, due to a longer history of treatment of patients carrying these viruses. However transmission of drug resistant non HIV type B is occurring. The small difference observed between acute and chronic infections confirms that mutations may persist over time. The high prevalence of resistance indicates that baseline sequencing should be considered in newly diagnosed patients who became infected in Europe.
LB2 ENFUVIRTIDE TORO STUDIES: 48 WEEK RESULTS CONFIRM 24 WEEK FINDINGS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. LB2)
C. Katlama1, K. Arastéh2, B. Clotet3, D.Cooper4, K. Henry5, J. Lalezari6, A. Lazzarin7, J. Montaner8, M. Nelson9, M. O’Hearn10, P. Piliero11, J. Reynes12, B. Trottier13, S. Walmsley14, R. DeMasi15, J. Delehanty15, J. Chung16, M. Salgo16
These data support the efficacy and safety of ENF+OB over OB through 48 weeks of treatment and substantiate the utility, tolerability and feasibility of long-term ENF therapy.
LB3 CLINICAL PROGRESSION WITH TRIPLE AND DUAL ANTIRETROVIRAL COMBINATION THERAPY IN HIV-1 INFECTION - SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. LB3)
Y. Yazdanpanah, D. Sissoko, M. Egger, Y. Mouton., M. Zwahlen, G. Chêne
In NRTI-experienced patients with advanced infection, comparisons between triple and dual antiretroviral therapy indicate that PI-based triple regimens are superior to regimens based on NNRTIs (nevirapine or delavirdine). This important finding should be confirmed in a trial directly comparing PI- and NNRTI-based triple regimens.
LB4 FAILURES OF ONE WEEK ON, ONE WEEK OFF ANTI-RETROVIRAL THERAPIES IN A RANDOMIZED TRIAL
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. LB4)
J. Ananworanich1, R. Nuesch1, M. Le Braz2, P. Chetchotisakd1, N. Khanna3, C. Ebnöther3, A. Vibhagool, S.Wicharuk1, S. Ubolyam1, K. Ruxrungtham1, H. Furrer3, M. Cavassini3, E. Bernasconi3, P. Vernazza3, S. Yerly1, D. Genné3, L. Perrin2, P. Phanupak1, D. Cooper4, B. Hirschel2, and the Swiss HIV Cohort Study
The week on, week off schedule, as tested in the Staccato study, showed an unacceptably high failure rate and was therefore terminated.
LB5 ALTERNATION OF ANTIRETROVIRAL DRUG REGIMENS FOR HIV INFECTION: A RANDOMIZED, CONTROLLED TRIAL
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. LB5)
J. Martínez-Picado1; E. Negredo2; L. Ruiz1; A. Shintani3; C.R. Fumaz2; C. Zala4; P. Domingo5; J. Vilaró6; J.M. Llibre7; P. Viciana8; K. Hertogs9; C. Boucher10; R.T. D'Aquila3; B. Clotet1, and the SWATCH Study Team
Patients receiving standard-of-care regimens A and B did not differ. Virologic failure over 48 weeks was delayed in the alternating therapy group compared with the pooled standard-of-care group (incidence rate, 1.2 events/1000 person-weeks [95% CI, 0.3 to 3.6 events/1000 person-weeks] vs. 4.8 events/1000 person-weeks [CI, 2.9 to 7.4 events/1000 person-weeks]; P= 0.01). Genotypic drug resistance emerged in 79% of patients in the standard-of-care group who experienced on-therapy treatment failure.
LB6 SIGNIFICANCE OF MODERN IMAGING PROCEDURES IN EVALUATING NEUROPATHOGENESIS OF HIV-1-RELATED BRAIN DISEASE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. LB6)
G. Arendt1, B.A. Haslinger1, H. Köller1, H.J. von Giesen1, C. Antke2, H.J. Wittsack3
Thus, conventional imaging procedures are not the right tool for research on virus associated brain disease, whereas functional imaging (PET and MRS) methods characterise subgroups of patients with early subclinical cerebral deficits. SPECT procedures give hints for the most irritated brain regions. Finally, molecular imaging techniques could be the right method for evaluating the molecular mechanisms destroying the brain in this devastating and disabling disease in relatively young patients.
LB7 REDUCING RISK OF HIV-1 TRANSMISSION FROM MOTHER TO INFANT THROUGH BREASTFEEDING USING ANTIRETROVIRAL PROPHYLAXIS IN INFANTS (SIMBA-STUDY)
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. LB7)
J. Vyankandondera1, S. Luchters2, E. Hassink2, N. Pakker2, F. Mmiro3, P. Okong4, P. Kituuka4, C. Ndugwa3 , N. Mukanka1, A. Beretta5, M. Imperiale Jr6, E. Loeliger7, M. Giuliano8, J. Lange2
The combination of antiretroviral prophylaxis and counselling on breastfeeding practices in infants receiving breastfeeding from HIV-1 infected mothers is very effective in preventing mother to infant transmission. This finding could have considerable public health implications on breastfeeding practices for HIV-1 positive women.
LB8 STRUCTURE ASSISTED RATIONAL ENV DESIGN FOR HIV VACCINE APPLICATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. LB8)
I.K. Srivastava, K. Hartog, E. Kan, V. Sharma, E. Martin, J. Donnelly, J. Ulmer, S. Barnett
Preliminary data suggest that double deletions introduced in the bridging sheets were effective in enhancing the neutralizing antibody responses against homologous isolate. Efforts are in progress to perform neutralization of heterologous primary isolates and epitope mapping studies.
| July 2003 | Wednesday 16th . 14:30-16:30
Session 46LB - Late Breakers
Late Breakers - Oral
Chair persons
Philippe Gallay, The Scripps Research Institute, La Jolla, USA
Jean-Michel Molina, Hospital Saint-Louis, Paris, France

LB9 THE IMPAIRED NK CELL FUNCTION IN HIV-1 INFECTION IS ASSOCIATED WITH A DEFECTIVE SURFACE EXPRESSION OF NKP46, NKP30 AND NKP44 RECEPTORS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. LB9)
M. Fogli1, A. De Maria1, P. Costa1, G. Murdaca1, F. Puppo1, A. Moretta2-3, L. Moretta2-3-4
Future analysis of aviremic treated patients could provide insights regarding the possibile mechanisms involved (viral, microenvironment) and the possibility of NK cell immune reconstitution during HAART.
LB10 CELL-TO-CELL TRANSFER OF HIV BETWEEN PRIMARY CD4 T CELLS THROUGH CD4 DEPENDENT ENDOCYTOSIS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. LB10)
J Blanco, B Clotet, J.A Esté
In conclusion, this is a first demonstration of a new mechanism of virus transmission between T cells, by which cellular contacts enhance CD4-dependent endocytic HIV uptake. Therefore, HIV can exploit CD4 T cells lacking the appropriate coreceptor as an itinerant virus reservoir that contributes to the spread of infection.
LB11 THE BLOCKING EFFECT OF NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR (NNRTIS) ON THE "NAKED" VIRUS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. LB11)
H.F. Njai1, K. Andries2, M.P. de Béthune2, L. Kestens1, P. Lewi3, G. Vanham1
This study will be useful to identify drugs that act on the free virus to prevent infection and to assess the role of drug combinations. The outcome can be used to select compounds for studies in animal models of vaginal infection (SCID mice and macaques).
LB12 THE ASSOCIATION BETWEEN DRUG RESISTANCE AND ADHERENCE DETERMINED BY TWO INDEPENDENT METHODS IN A LARGE COHORT OF DRUG NAÏVE INDIVIDUALS STARTING TRIPLE THERAPY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. LB12)
P.R. Harrigan1-2, W.Y. Dong1, C. Alexander1, B. Yip1, L. Ting1, B. Wynhoven1, J. Woodward1, T. Mo1, R. Hogg1, J. Montaner1-2
The highest risks for developing drug resistance in drug naïve individuals starting triple therapy were associated with high baseline viral loads, prescription refills nearing 60-90% and/or low plasma drug levels.
LB13 ATAZANAVIR AND EFAVIRENZ, EACH COMBINED WITH FIXED-DOSE ZIDOVUDINE AND LAMIVUDINE, HAVE SIMILAR EFFECTS ON BODY FAT DISTRIBUTION IN ANTIRETROVIRAL-NAÏVE PATIENTS: 48-WEEK RESULTS FROM THE METABOLIC SUBSTUDY OF BMS AI424-034
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. LB13)
Joseph G. Jemsek1, Eduardo Arathoon2, Massimo Arlotti3, Carlos Perez4, Nestor Sosa5, Vadim Pokrovskiy6, Michael Giordano7, Alexandra Thiry7, and Michael Soccodato7
Atazanavir and efavirenz produced comparable and proportional effects on body fat distribution at 48 weeks when administered with fixed-dose zidovudine and lamivudine to antiretroviral-naïve patients. The pattern of fat increase observed on both regimens was consistent with weight gain and not with the patterns for central adiposity (disproportionate increase in truncal fat) or lipoatrophy (loss of appendicular fat) associated with the development of lipodystrophy.
LB14 EXTENDED FOLLOW-UP OF THE ANRS 093 RANDOMIZED STUDY: EVALUATION OF ALVAC 1433 AND HIV LIPOPEPTIDE (LIPO-6T) VACCINES COMBINED WITH SC IL-2 IN CHRONICALLY HIV-INFECTED PATIENTS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. LB14)
Y. Lévy1, C. Durier1, A.S. Lascaux1, V. Meiffrédy1, C. Goujard1, C. Rouzioux1, R. Elhabib2, J.G. Guillet1, J.F. Delfraissy1, J.P. Aboulker1, and the ANRS 093 study group
Long term FU showed that the therapeutic vaccine strategy was safe and that its beneficial effect on the viral set point after stopping HAART was sustained around 9 months.
LB15 ANTI HIV-1 ACTIVITY OF SPD754 A NEW NRTI: RESULTS OF A 10 DAY MONOTHERAPY STUDY IN TREATMENT NAÏVE HIV PATIENTS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. LB15)
P. Cahn1, J. Lange2, I. Cassetti3, J. Sawyer4, C. Zala1, M. Rolon1, R. Bologna3, L. Shiveley5
SPD754 is a new NRTI that is highly effective against HIV-1 in patients. It is well tolerated and warrants further investigation in longer term treatment studies.
LB16 ANTIRETROVIRAL ACTIVITY, SAFETY AND PHARMACOKINETICS OF TMC114, A NEXT-GENERATION HIV-1 PROTEASE INHIBITOR (PI), IN MULTIPLE PI- EXPERIENCED PATIENTS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. LB16)
K. Arasteh1, N. Clumeck2, A. Pozniak3, H. Jaeger4, M. De Pauw5, H. Muller5, M. Peeters5, R. Hoetelmans5, S. De Meyer5, W. Parys6, R. van der Geest5
TMC114/r exhibited potent antiretroviral activity and favorable pharmacokinetics when given for 14 days to multiple PI-experienced patients currently failing a PI-containing regimen. For the TMC114/r arms, maximum and median changes in HIV-1 RNA (log10) were -2.49 and -1.35 copies/ml, respectively. TMC114/r was generally well tolerated.
Session 51PO - Poster
Virology/Viral Pathogenesis
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 51.01PO - Poster
Molecular Epidemiology
234 MOLECULAR EPIDEMIOLOGY OF HIV IN GHANA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 234)
L Fischetti1, D Candotti1, O Opare-Sem2 and JP Allain1
In asymptomatic blood donors infected with CRF02_AG, the viral load was significantly higher than in donors infected with other molecular forms of HIV-1. Irrespective of clinical condition, CRF02_AG is the predominant molecular form of HIV-1 in Kumasi, while straight subtypes of HIV-1 strains are relatively rare (4.5%). The significantly higher viral load of CRF02_AG is compatible with a higher infectivity.
235 HIV-1 SUBTYPE B POLYMORPHISM IN SOUTH AMERICA: CHARACTERIZATION OF PROVIRAL DNA ISOLATES FROM VENEZUELA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 235)
E Castro1, M Moreno1, L Deibis1, S Salmen2, L Berrueta2, and G Echeverría de Pérez1
Our results suggest that genomic polymorphism differences among subtype B strains from Venezuela can be related to geographical regions. Thus, we cannot determine the meaning of this polymorphism in SAC, it seems that gag/env HMA can be also an appropriate tool to compare HIV-1 subtype B strains within subepidemics of South America where nucleotide sequencing is not widely available for molecular surveillance and vaccine strategies move on to clinical trails.
236 RECOMBINANT BF INTERSUBTYPES OF HIV-1 IN A POPULATION OF INJECTING DRUG USERS IN ARGENTINA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 236)
M Vignoles1, A Espinosa2, M Gómez Carrillo1, H Sheppard2, R Donovan2, L Martínez Peralta1, D Rossi3, G Radulich4, H Salomón1 and M Weissenbacher1
Genomic characterization by nucleotide sequencing of the HIV-1 variants is an important tool for the understanding of the virus transmission, dissemination and epidemiology in the community. Forty percent of the notified AIDS cases in Argentina represent individuals who have acquired the virus through the sharing of drug injecting equipment.
237 GENETIC DIVERSITY OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 IN ANGOLA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 237)
I Bártolo1,2, A Gama2, M Epalanga3 and N Taveira1,2
This is the first report on HIV-1 subtypes in Angola. Further studies are in progress to better characterise the genetic diversity of HIV-1 in Angola. This work will guide future vaccine strategies and may aid in the establishment and management of antiretroviral therapy in Angola.
238 EVOLUTION OF HIV-1 SUBTYPES IN NORTHERN TANZANIA: A RETROSPECTIVE STUDY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 238)
BM Nyombi1,2, S Jeansson4, M Holberg-Petersen4, W Nkya1, L Barongo1, G Bjune2 and C Holm-Hansen2,3
Development of effective vaccine against HIV-1 has faced a set back due to its great genetic diversity. However, in different geographical areas vaccines trials are underway depending on the prevalent HIV subtypes. Serological assays have been used in HIV-1 subtyping.
239 IDENTIFICATION AND DISTRIBUTION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (HIV-1) GENETIC DIVERSITY AND PROTEASE INHIBITOR RESISTANCE-ASSOCIATED MUTATIONS IN SHANGHAI, P.R. CHINA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 239)
P Zhong1-3, LY Kang2,3, QC Pan2,3, F Konings4, S Burda1, LY Ma1, YL Xue2,3, XH Zheng2,3, ZC Jin2,3 and P Nyambi1-5
This study reveals the presence of multiple HIV-1 subtypes and recombinants infecting Shanghai residents. This study also reveals that viruses infecting these treatment-naïve patients have acquired both primary and/or secondary mutations in their protease genes. These studies should provide the basis for further epidemiological surveys of HIV-1 subtypes and set strategies for treatment intervention and vaccine programmes.
240 CHARACTERIZATION OF NEAR FULL-LENGTH GENOME SEQUENCES OF HIV-1 BF RECOMBINANT VIRUSES FROM CHILE, VENEZUELA AND SPAIN
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 240)
M Sierra1, MM Thomson1, G Casado1, E Delgado1, Y Vega1, E Vázquez de Parga1, R Carmona1, M Muñoz1, L Pérez-Álvarez1, G Contreras1, L Medrano1, M Rios2, G Echeverría3, J Colomina4, C Ojea de Castro5 and R Nájera1
This is the first report of full length genome analysis of HIV-1 BF recombinants from Chile, Venezuela and Spain. The results support their relation with BF recombinants from Argentina, and the generation of some of them by successive rounds of recombination.
241 FULL GENOME CHARACTERIZATION OF HIV-1 UNIQUE AND CIRCULATING RECOMBINANT VIRUSES OF AFRICAN ORIGIN IN GALICIA (NORTHWESTERN SPAIN)
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 241)
G Casado, M Thomson, E Delgado, M Sierra, E Vazquez de Parga, R Carmona, M Muñoz, Y Vega, L Perez-Alvarez, G Contreras, L Medrano, R Najera and the Resistance Group to Antiretrovirals in Galicia
Among the analysed genetic forms, seven recombinants of probable African ancestry, four were novel recombinants with unique mosaic structures, three of which were related to unique African recombinants in part of their genomes. This suggests that secondary recombination of HIV-1 mosaic viruses is relatively common in sub-Saharan Africa.
242 MUTATIONS RELATED TO PRIMARY RESISTANCE TO ANTIRETROVIRALS AMONG NEWLY HIV-1 INFECTED INDIVIDUALS IN BELO HORIZONTE-BRAZIL
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 242)
A Waléria-Aleixo, A Tanuri, SC Cleto and DB Greco
We have detected a substantial number of individuals with HIV-1 variants with mutations associated to ARV resistance. These findings warrant the establishment of sentinel studies to further evaluate this trend and the possibility of performing genotyping for naïve patients.
243 MOLECULAR CHARACTERIZATION OF HIV-1 ISOLATES FROM 200 INFECTED INDIVIDUALS RECRUITED IN 2001 AND 2002 IN THE SOUTH PART OF VIETNAM
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 243)
NTH Lan1, P Pinson-Recordon2, PV Hung1, NTV Uyen1, TTX Lien3, HT Tien1, M Faure2, MH Schrive2, I Pellegrin2, I Garrigue2, ME Lafon2, JP Aboulker4, F Barré-Sinoussi5 and HJ Fleury2
There is so far no dynamic process of HIV-1 subtypes in south Vietnam.
244 MOLECULAR EPIDEMIOLOGY OF THE RECENT HIV-1 EPIDEMIC IN THE NORTHWESTERN PART OF THE RUSSIAN FEDERATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 244)
T Smolskaya1, E Golovanova1, V Zetterberg2, K Sevastianova2, N Kevlova1, K Liitsola2, P Leinikki2 and M Salminen2
The subtype A-EastEur strain has gained a very wide in different territories of the N-W of the RF. The minimal variation between the strains supports the view of a contiguous network of probably IDU-driven transmission in the entire country. This suggests that one possible explanation for the rapid spread is dispersal of the virus by travel of infected carriers, possibly drug traffickers who are themselves users. Demonstration of the CRF03-ABkal153 strain in the Vologda region shows that these networks may be very far-reaching.
245 IS NATURAL SELECTION INVOLVED IN THE RAPID EXPANSION OF GWGR SUBTYPE B VARIANT IN BRAZIL?
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 245)
ME Pinto1, M Schechter2, C Struchiner1, AB Miranda1 and CAM Russo2
GWGR sequences formed a single cluster in the phylogenetic tree, regardless of their geographic origin, strongly suggesting a single origin for this signature pattern. Phylogenetic analyses and epidemiological data suggest that the dispersion of the GWGR variant in Brazil was rapid. Thus, natural selection is probably involved in the spread of the GWGR variant in the country.
246 A CONSTANT AND EXTREMELY HIGH GENETIC DIVERSITY OF HIV-1 GROUP M STRAINS IN THE DEMOCRATIC REPUBLIC OF CONGO, BETWEEN 1997 AND 2002
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 246)
N Vidal1, C Mulanga1, S Edidi Bazepeo2, D Valéa1, N Mama2, J Kasali Mwamba3, M Peeters1, E Delaporte1 and F Lepira4
Overall, the high number of HIV-1 subtypes co-circulating, the high intra-subtype diversity, the high numbers of possible recombinant viruses as well as the different unclassified strains are all in agreement with an old and mature epidemic in the DRC, suggesting that this region is the epicenter of HIV-1 group M. Five years of ethic war and foreign invasions did not influence the subtype distribution nor the HIV prevalence in DRC.
247 FULL-LENGTH GENOME ANALYSIS REVEALS THAT HIV-1 SUBTYPE A STRAINS FROM COUNTRIES OF THE FORMER SOVIET UNION REPRESENT A NOVEL SUBSUBTYPE WITHIN SUBTYPE A
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 247)
A Masharsky, N Klimov and A Kozlov
HIV-1 subtype A strains from the FSU represent a novel subsubtype and apparently originated from some African subtype A lineage which isn’t found in Africa at present. It resembles origin of HIV-1 subtype B prevalent in North America and Western Europe from African subtype D.
248 ANALYSIS OF FULL-LENGTH GENOMES OF HIV-1 BF RECOMBINANT VIRUSES FROM BRAZIL
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 248)
MM Thomson1, M Sierra1, A Tanuri2, M Morgado3, G Casado1, E Delgado1, R Carmona1, M Muñoz1, E Vázquez-de Parga1, Y Vega1, G Contreras1, L Medrano1, L Pérez-Álvarez1 and R Nájera1
Five new near full-length genomes of HIV-1 BF recombinant viruses from Brazil have been characterized (previously, only one was available). Each recombinant has a unique structure and appears to have an independent origin, and, in contrast to findings in Argentina and Uruguay, none of the analysed Brazilian recombinants is related to CRF12_BF.
249 EPIDEMIOLOGIC AND MOLECULAR CHARACTERIZATION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 IN SOUTHERN BRAZIL
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 249)
MA Soares1, EAJM Soares1, RP Santos2, JA Pellegrini2, E Sprinz2 and A Tanuri1
Human immunodeficiency virus subtype C is the most prevalent subtype in the world. Despite its recent introduction in Brazil, HIV-1C already prevails in the southernmost state of Brazil, Rio Grande do Sul. This unique HIV epidemiology in Brazil has prompted us to characterize that population in detail.
250 HIV-1 EVOLUTION TO PATHOGENIC FORMS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 250)
MD Hill
HIV-1 evolves over the course of disease altering its tropism, immunogenicity and rapidity of growth. In order to identify changes that predicate disease progression, a meta-analysis was undertaken of studies that had longitudinally derived gene sequences surrounding the V3 envelope region along with CD4 data. Only sequences derived by means that acquire distinct members of a population were included, e.g., clones.
251 DISTRIBUTION OF HIV-1 SUBTYPES IN NOVOSIBIRSK REGION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 251)
AG Pokrovsky, NM Gashnikova and AV Totmenin
Analysis of the nucleotide sequences of the genomes of HIV-1 isolates from the main foci of the world suggests that the HIV-1 subtypes are unevenly distributed. Assessment of HIV-1 subtypes tending to be confined to certain areas is an important step towards a better understanding of the dynamics of these epidemics, better vaccine development, and better diagnosis.
252 CHARACTERIZATION OF HIV-1 GROUP N ISOLATES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 252)
F Simon1–5, P Roques1, D Robertson2, S Souquière1, A Ayouba3, C Apetrei1, E Nerrienet3, F Barré-Sinoussi4 and M Müller-Trutwin4
HIV-1 groups M, N and O have been probably introduced into the human population as a result of independent cross-species transmissions of SIVcpz from Pan troglodytes. We reported previously the full-length genome of group N prototype YBF30, as well as partial sequences from HIV-1 N YBF105, these viruses showing a close relationship with SIVcpz in env.
254 PREVALENCE OF NON-TYPE B HIV-1 IN CENTRAL ITALY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 254)
ML Vatteroni1, F Maggi1, M Pistello1, S Frateschi1, C Fornai1, R Iapoce2, F Menichetti2 and M Bendinelli1
These finding indicate that in our area subtype F is currently the predominant non-B strain and emphasize the need to monitor the diffusion of HIV-1 subtypes for epidemiological, prophylactic and therapeutic purposes.
255 NEAR FULL-LENGTH GENOME CHARACTERIZATION OF HIV-1 CRF14-BG AND UNIQUE BG RECOMBINANTS FROM GALICIA (SPAIN)
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 255)
E Delgado, G Casado, MM Thomson, M Sierra, M Muñoz, R Carmona, Y Vega, E Vázquez de Parga, L Pérez-Álvarez, G Contreras, L Medrano and R Nájera, the Spanish Group for HIV Studies in Galicia
Diverse HIV-1 BG recombinants have been characterized in Galicia by full-length genome analysis, including CRF14_BG viruses, unique secondary CRF14_BG/subtype B or G recombinants, and other unique BG recombinants. The relatively frequent finding of unique BG recombinants in Galicia attests to the frequent occurrence of dual infections, which may have implications for vaccine development.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 51.02PO - Poster
HIV Diversity
256 PREDICTORS OF HIV SEROSTATUS AMONG HIV DISCORDANT COUPLES IN LUSAKA, ZAMBIA AND FEMALE ANTENATAL CLINIC ATTENDANTS IN KIGALI, RWANDA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 256)
K Modjarrad1, I Zulu2, E Karita3, N Kancheya2, E Funkhouser1 and S Allen1
The results of our study indicate that clinical and laboratory markers of HIV disease should be tailored according to local norms, by gender, before they are applied to any diagnostic algorithm or staging system.
257 SEQUENCE VARIATIONS IN THE ENV V3-V4 REGION OF HIV-1 PREDOMINANT SUBTYPE B AND C STRAINS CIRCULATING IN CHINA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 257)
H Liang, K Hong, M Wei, Y Quan, H Xing, L Shi and Y Shao
The majority of variation in both subtypes B and C strains occurred in the V4 rather than the V3 region. It is important that our study found for the first time the V3 loop was more conservative than the V3 upstream region and C3 region for subtype C. Calculations of the Ks/Ka ratios throughout the V3-V4 region demonstrate that significant selective pressures experienced during the rapid horizontal spread of virus in the Chinese HIV-1-infected population may have directed change in the V3 loop for the subtype B strain and the V4 loop for the subtype C strain. These results will contribute to the policy of AIDS prevention and control and the ongoing development of AIDS vaccine.
258 GENOMIC DIVERSITY OF HUMAN IMMUNODEFICIENCY VIRUS TYPE-I (HIV-1) IN INDIA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 258)
RM Gupta1, S Pradeep2, AK Sahni3, VVSP Prasad2 and A Rai4
All these studies concluded that HIV-1 subtype C was predominant in India accounting for 85–90 % of all isolates. Other subtypes observed included subtypes A, Thai B, E and putative recombinants. Also, it is evident that as the epidemic evolves, subtype C strains are likely to replace subtype Thai B in the Northeast.
259 HIV PHYLOGENETIC ANALYSIS AND GENETIC CHARACTERIZATION IN NEWLY INFECTED INDIVIDUALS IN BELO HORIZONTE-BRAZIL
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 259)
A Waléria-Aleixo, A Tanuri, SC Cleto and DB Greco
Subtype B was the most prevalent in this cohort. There was no potentially HIV-1 recombinant genomes in the analysed sample. There was a high divergence of V3 loop region from the B consensus and this may reflect very different biological and immunological characteristics, which must be further evaluated.
260 HIV-1 GROUP M CLADES INFECTING PERSONS IN RURAL VILLAGES IN CAMEROON
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 260)
M Tongo1,2, A Nanfack1, L Ewane1, P Zhong3, S Burda3, M Urbanski3, A Anyambod1, A Bih1, L Zekeng1 and P Nyambi3
This study suggest that the HIV-1 diversity in rural villages in Cameroon is at least as broad as has been observed in major cities of Cameroon and that multiple HIV-1 group M subtypes are infecting persons living in countryside of Cameroon.
261 HIV-1 GENETIC DIVERSITY AND CLADE INTERPENETRATION IN A COHORT OF PREGNANT WOMEN IN MONTREAL, CANADA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 261)
H Soudeyns1,2,6, BS Akouamba1,2, J Samson3, K Deroy1,2, H Charest4, M Boucher3–5 and N Lapointe3–6
Our results highlight the relative epidemiological importance of non-clade B variants in antenatal populations, underscore the influence of recent population movements on HIV-1 clade interpenetration, and identify a group of subjects that could be preferentially targeted for surveillance and intervention.
262 PHENOTYPIC ANALYSES OF HIV-1 SUBTYPE-SPECIFIC PROMOTERS IN VIVO
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 262)
M Centlivre, P Sommer, M Michel, R Ho Tsong-Fang, V Monceaux, B Hurtrel, S Wain-Hobson and M Sala Pasteur Institute, Paris, France
The HIV-1 transcriptional promoter localized in the ‘long terminal repeat’ (LTR) is extremely polymorphic and subtypes specific. The role played by this polymorphism in HIV-1-induced pathogenesis is still controversial. To address this subject in vivo, SIV/HIV chimeras have been constructed from a STR SIVmac239 clone (3′STR-SIV-wt; STR for ‘short terminal repeat’).
263 EVOLUTION AND DOMINANCE OF A NEW HIV RECOMBINANT FROM A PATIENT INFECTED WITH TWO SUBTYPES IN WESTERN KENYA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 263)
H Ichimura1–3, EM Songok1,2, RM Lwembe1,2, IO Genga2, RW Lihana2, RM Kibaya2, K Kobayashi1, N Ndembi1, I Oishi3 and F Okoth2
Recombinant forms of HIV-1 have been demonstrated in HIV-1 infected individuals in various studies. However, in vivo evolution of the recombinants in individuals infected with multiple subtypes is not well known. We present here a case of a mother in Kenya initially coinfected with two different subtypes but developed one recombinant form of the two HIV-1 subtypes during follow-up.
264 VIRAL POPULATIONS IN PLASMA AND PERIPHERAL BLOOD MONONUCLEAR CELLS IN HIV-2-INFECTED INDIVIDUALS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 264)
H Barroso and N Taveira
These results suggest that in HIV-2 infection there are different populations in both compartments, and that the viral population in plasma has its origin in the circulating PBMCs. HIV-2 seems to evolve more rapidly in plasma than in PBMCs probably due to the strong selective pressure imposed by the humoral immune system.
265 ‘HIV-U’: HIGHLY DIVERGENT HIV UNKNOWN STRAINS OR UNCOMMON NATURAL HISTORY OF HIV INFECTION?
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 265)
JC Plantier1, M Gueudin1, F Damond2, V Lemée1 and F Simon3
CRF02_AG or G-like are increasingly imported in Europe. These atypical infections involving recombinant related forms plaid fo further clinical and molecular investigations to explain this low level of replication and to reinforce the diagnosis capacity particularly in blood banking.
266 POLYMORPHISM ANALYSIS OF GAG CLEAVAGE SITES AND P6 LATE DOMAIN IN PI-RESISTANT AND SUSCEPTIBLE HIV-1 ISOLATES FROM B AND F CLADES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 266)
PA Brindeiro1, RM Brindeiro1, C Mortensen2 and A Tanuri1
We can infer a tendency to differential co-evolution of gag cleavage sites between those two clades studied. The role of the four different p6 L domain polymorphic patterns found to the resistance to PIs may be further accessed by fitness assay as well as gag-pol phenotyping using a recombinant virus assay.
267 EVIDENCE FOR EARLY INTRODUCTION OF NON-B HIV-1 SUBTYPES IN FRANCE AND PHENOTYPIC ANALYSES OF ENV GENES OBTAINED FROM SYMPTOMATIC PRIMARY INFECTION SAMPLES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 267)
L Vachot1, Y Ataman-Onal1, C Terrat1, PY Durand1, F Biron2 and B Verrier1
Using blood samples from primary HIV-1 infection (PHI) patients obtained between 1992 and 1996, we assessed the introduction of HIV-1 variants in Lyon, France and we studied the envelope proteins obtained from these PHI samples for fusion capacity and co-receptor usage.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 51.03PO - Poster
Viral Dynamics and Fitness
268 COMPARING VIRAL FITNESS OF HIV-1 GROUP M (SUBTYPES A, B, C, D AND CRF01), HIV-1 GROUP O AND HIV-2 ISOLATES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 268)
KK Ariën1, A Abraha2, RM Troyer2, ME Quinones-Mateu3, G van der Groen4, R Colebunders5, L Kestens1, L Heyndrickx4, EJ Arts2 and G Vanham1
Recently, we have shown that HIV-1 group M subtype C viruses are less fit than subtype B, which may be related to subtype distribution and spread. In this study, we compared relative replicative capacity of HIV-1 group M, group O and HIV-2.
269 IMPACT OF AN INCREASING NUMBER OF HIV RESISTANCE MUTATIONS ON VIROLOGIC AND IMMUNOLOGIC OUTCOMES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 269)
N Machouf, G Lalonde and T Murphy
The biphasic decrease and then increase in plasma viraemia with increasing mutation scores suggested an initial loss and then recovery of viral fitness. However, in individual patients, an increase in the score over time was neither beneficial nor harmful, suggesting that the changes in mutation score had a minimal clinical impact.
270 RARE SI, CXCR4-TROPIC HIV-1 ISOLATES OF SUBTYPE C ARE LESS FIT THAN ANY OTHER GROUP M HIV-1 ISOLATE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 270)
EJ Arts1, A Abraha1, E Fraundorf1, A Marozsan1, B Johnston2 and D Katzenstein2
These findings suggest that subtype C ex vivo fitness in relation to other HIV-1 subtypes does increase with a switch from an NSI/X4 to an SI/X4 phenotype. Decreased replication efficiency appears intrinsic to any subtype C HIV-1 isolate and may be related to dominance of this subtype in the epidemic.
271 LONG TERM DURABILITY OF IMPAIRED HIV REPLICATION CAPACITY IN PATIENTS MAINTAINED ON A STABLE TREATMENT REGIMEN DESPITE LOW-LEVEL VIROLOGICAL FAILURE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 271)
MB Goetz, F Moatamed, T Wrin, K Dawson and N Hellmann
Decreased RC and CD4 improvements may persist for up to 4–5 years despite increasing R and continued VF. By demonstrating the durability of impaired RC and stable CD4 in adherent P, these data provide further support for not altering Rx despite a VL >1000 copies/ml in selected P with decreased RC.
272 IN VITRO SUSCEPTIBILITY TO PROTEASE INHIBITOR FROM SUBTYPE C OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 ISOLATES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 272)
LMF Gonzalez1, RM Brindeiro1, M Tarin2, A Calazans1, MA Soares1, S Cassol2 and A Tanuri1
In order to characterize the impact of genetic polymorphisms on the susceptibility to protease inhibitors from subtype C strains of human immunodeficiency virus type 1 a subtype B protease originated from an infectious clone was modified through site-direct mutagenesis to include the amino acid residue signatures of subtype C viruses (I15V, M36I, R41K, H69K, L89M) with (clone C6) or without (clone C5) a I93L polymorphism present as molecular signature of worldwide subtype C protease.
273 HIV REPLICATION CAPACITY (RC) PREDICTS HIV CLINICAL PROGRESSION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 273)
E Daar1, K Kesler2, S Donfield2, T Wrin3, C Petropoulos3, N Hellmann3 and the Hemophilia Growth and Development Study
RC is variable in a natural history cohort with minimal ART exposure. RC also appears to influence the natural history of HIV disease since modest decreases are associated with lower HIV RNA, higher CD4 cells and delayed progression to AIDS. These data suggest that even greater clinical benefits might be associated with the more profound RC reductions seen in those with multidrug-resistant HIV.
274 CONTRACEPTIVE USE IN HIV-POSITIVE WOMEN
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 274)
I Heard1, V Potard2, D Costagliola2 and M Kazatchkine1
Among seroconcordant couples, no birth control was reported in a third of the cases, indicating that contraceptive counseling should be considered for such couples. In serodiscordant couples, a sustained decrease in the use of EC since the introduction of HAART may be suggestive of a wish for planned pregnancies.
275 ENHANCEMENT OF HIV-1 VIRAL PRODUCTION IN VITRO BY SUPERINFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 275)
P Fernández Larrosa, A Ceballos, R Rabinovich, S Marquina, and L Martínez Peralta
Superinfection with HIV-1 occurs in vitro and in vivo, and is considered to be the main cause of the high frequency of circulating recombinant forms worldwide. Viral production is normally high in patients and different viral variants accumulate over time causing the necessary conditions for superinfection. Previous experiments in our laboratory suggested pseudotype production due to superinfection with different HIV-1 strains.
276 FREQUENCY AND INFECTIOUSNESS OF HIV-1 PROTEASE INHIBITOR RESISTANCE VARIANTS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 276)
M Carobene1, A Rubio1, G Turk1, M Saracco1, M Wainberg2 and H Salomon1
The low frequency of appearance of mutations at positions 84 and 90 in the PR of our samples may be due to low fitness and/or infectiousness of the variants harbouring these mutations.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 51.04PO - Poster
HIV-1 and HIV-2
277 REAL-TIME PCR TECHNOLOGY DEVELOPED FOR THE DETECTION OF HIV-1 RNA AND HIV-2 DNA PERMITS AN INEXPENSIVE AND EARLY DIAGNOSIS OF HIV INFECTION IN AFRICAN NEONATES FROM CÔTE D’IVOIRE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 277)
F Rouet1, N Coulibaly1, D Ekouevi2, ML Chaix3, M Burgard3, L Bequet3, F Dabis4 and C Rouzioux2, for the ANRS 1201/1202 Ditrame-Plus Study Group
HIV-1 and HIV-2 realtime PCR assays appear to be attractive tools for early diagnosis of paediatric HIV infection in Africa, as they are based on an easy, rapid, and inexpensive technology.
278 SURVIVAL OF HIV-2, HTLV-I OR DUALLY INFECTED SUBJECTS IN A RURAL AREA OF WEST AFRICA: A COMMUNITY-BASED STUDY WITH 12 YEARS OF FOLLOW-UP
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 278)
MF Schim van der Loeff1,2, B Holmgren3,4, T Vincent4, K Ariyoshi2,5, S Andersson6, F Dias7, P Aaby3,4 and H Whittle2
HIV-2 infection is associated with a significant excess mortality rate in young people. HTLV-I infection is associated with an increased mortality rate in all age groups. HTLV-I and HIV-2 exert their effects on mortality independently.
279 EPIDEMIOLOGY OF HIV-2 INFECTION IN SPAIN
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 279)
C Toro1, B Rodés1, A Aguilera2, E Caballero3, C Rodríguez4, E Poveda1, C Tuset5, J García6, R Ortiz de Lejarazu7, J Eirós7, R Benito8, E Calderon9 and V Soriano1, the HIV-2 Spanish Study Group
HIV-2 infection is currently circulating in Spain, although with low prevalence and without evidence for an increase over time. The main HIV-2 subtypes, A and B, are recognized in both Spaniards and Africans.
280 MULTICENTRE PERFORMANCE EVALUATION OF NUCLISENS EASYQ HIV-1 V1.1
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 280)
T Oosterlaken1, V Ferre2, V Soriano3, C de Mendosa3, M Segondy4, B Montès4, H Cuypers5, M Koppelman5, R Ehren1 and I Berghuis1
The NucliSens EasyQ HIV-1 v1.1 assay combines an excellent analytical and clinical performance as shown in this European multicentre study. The assay’s real-time amplification/detection format provides a user convenient testing procedure and high-throughput options.
281 CHARACTERIZATION OF HIV-2 ISOLATES FROM INDIAN PATIENTS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 281)
S Kulkarni, N Jatkar, S Jadhav, K Agnihotri, R Kulkarni and S Tripathy
Chemokine receptors play significant role in HIV pathogenesis. Coreceptor usage by primary HIV isolates varies according to the biological phenotype and serves as a marker for advanced disease stage. HIV-1 subtype B infections are characterized by shift from CCR5 to CXCR4 phenotype during disease progression. Such shift is not seen in subtype C infections, including Indian strains.
282 NO EVIDENCE FOR RECOMBINATION BETWEEN HIV-1 AND HIV-2 IN DUALLY INFECTED INDIVIDUALS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 282)
ME Curlin1, GS Gottlieb1, SE Hawes1, PS Sow2, I Ndoye3, CW Critchlow1, NB Kiviat1 and JI Mullins1
Recombination between HIV-1 and HIV-2 resulting in chimeric viruses was not detected in vivo. Although genetic recombination between HIV-1 and HIV-2 may occur, our data suggest that such recombinants may have little evolutionary or pathogenic consequence.
283 A GENETIC SYSTEM TO STUDY PROTEOLYTIC ACTIVITY IN ESCHERICHIA COLI: STUDY OF HIV PROTEASE STRUCTURE–FUNCTION RELATIONSHIP
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 283)
N Dautin, G Karimova and D Ladant
The protease (PR) from human immunodeficiency virus (HIV) is essential for viral replication: this aspartyl protease, active only as a dimer, is responsible for cleavage of the viral polyprotein precursors (Gag and Gag-Pol), to release the functional mature proteins. In this work we have studied the structure function relationships of the HIV protease by combining a previously designed genetic test to detect proteolytic activity in Escherichia coli and a bacterial two-hybrid assay to analyse PR dimerization.
284 RECOMBINANT HUMAN GROWTH HORMONE (r-hGH) DOES NOT AFFECT THE ACTIVITY OF ANTIRETROVIRAL AGENTS AGAINST WILD-TYPE AND RESISTANT HUMAN IMMUNODEFICIENCY VIRUS-1 (HIV-1)
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 284)
MA Wainberg1, BG Brenner1, JM Gertner2, S Kenley2 and C Olivier3
The anti-HIV effects of commonly used antiretroviral drugs in PMBC were not altered or inhibited by rhGH. These in vitro data suggest that the use of r-hGH in HIV-infected patients undergoing active antiretroviral therapy does not promote viral replication.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 51.05PO - Poster
SIV and HIV-Related Viruses
285 MOLECULAR CHARACTERIZATIO OF PRIMATE LENTIVIRUSES FROM THREE CERCOPITHECUS SPECIES: MONA DENTI, ASCANIUS AND DE BRAZZA’S
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 285)
S Saragosti2, M Ekwalanga1, MC Dazza2, M Mende3, P Bitchou3 and K Bin Shamara1
Phylogeny of the Simian lentiviruses suggests a host-dependent evolution of SIV. In order to complete the evolutionary history of the simian immunodeficiency viruses, we are searching new monkeys’ species infected with lentiviruses in DRC (D.R. Congo). In a serosurvey of wild-born primates sold as pet in Kinshasa, we identified three monkeys, harbouring HIV/SIV cross-reactive antibodies, which sera were reactive with the three HIV-2 commercial diagnostic kits we used.
286 NON-INVASIVE DETECTION OF SIVsm IN FREE-LIVING SOOTY MANGABEY TROOPS FROM SIERRA LEONE (SL). EVIDENCE OF A SIERRA LEONE SUBCLUSTER IN THE SIVsm LINEAGE AND RELATIONSHIP TO USA ISOLATES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 286)
B Ling, P Telfer, P Reed, C Apetrei and PA Marx
We developed a non-invasive method for SIVsm virion RNA in fecal samples of captive sooty mangabeys (SMs) at the Tulane National Primate Research Center (TNPRC). Three of the four new lineages of SIVsm were first detected by this method.
287 STRUCTURED REGIONS WITHIN THE R-U5 INTRON OF SIMIAN IMMUNODEFICIENCY VIRUS CONTRIBUTE TO VIRAL RNA PACKAGING AND DIMERIZATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 287)
JB Whitney, B Spira and MA Wainberg
Our results show that elements within this region of the SIV leader contribute to the efficiency RNA packaging, with the largest impairments seen with disruptions to the poly-A stem. Similar mutations in the poly-A stem also impair RNA dimerization. Therefore, we have identified sequences within the SIV R-U5 region that are necessary but not sufficient for RNA encapsidation and that contribute to RNA dimerization. The disruption of these sequences also dramatically impairs viral replication and this correlates with discrete blocks in replication.
288 SIVmnd TYPE 1 AND TYPE 2 INFECT MACAQUE RHESUS AND INDUCE MID-TERM SUPPRESSION OF CD4 CELLS IN CONTRAST TO INFECTION OF NATURAL HOST (MANDRILLS)
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 288)
S Souquière1, R Onanga1, P Ngari1, M Makuwa1, O Bourry2, S Breton2, F Simon3 and P Roques1,4
The two types of SIVmnd infection induce high viraemia during primary infection in macaques as like infection in mandrills. In contrast, decrease of CD3/CD4 is observed only in macaque models. In chronic phase, viral load in plasma and PBMC are lower in macaques than in mandrills. These differences between macaque and mandrill models contribute towards a better understanding of SIV infection.
289 VISUALIZING CYTOKINES IN TISSUE: AN ADDED DIMENSION TO EVALUATION OF SIV INFECTION IN RHESUS MACAQUE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 289)
X Alvarez, G Ramesh, V Schoof, J Borda, K Sestak, R Veazy and A Lackner
Techniques for identifying infectious agents in tissues and characterizing the host immune response in blood are well developed. These techniques are, however, of limited value for examination of the host immune response in situ or when multiple markers are needed to identify cells producing cytokines in situ.
290 STLV INFECTION IN WILD PRIMATE POPULATIONS IN CAMEROON: EVIDENCE FOR DUAL STLV-1 AND STLV-3 INFECTION IN CERCOCEBUS AGILIS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 290)
V Courgnaud1, F Liegeois1, S de Vos1, C Butel1, S Van Dooren3, S Loul2, B Abela2, E Mpoudi-Ngole2, AM Vandamme3, E Delaporte1 and M Peeters1
These data document for the first time that: (1) a substantial proportion of wildliving monkeys in Cameroon is STLV infected; (2) STLV-1+3 cocirculate in the same species; (3) dual infection with STLV-1 and STLV-3 in C. agilis; and (4) humans are exposed to STLV-1 and -3 infections.
291 ISOLATION OF SIVMND-2 FROM DOMESTICATED MANDRILLUS SPHINX OF SOUTHERN CAMEROON
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 291)
C Ngansop1, N Ndembi1,2, H Ichimura1, P Kenmogne1 and L Kaptue1
In an epidemiological survey of human immunodefieciency virus (HIV) a case of a human infected with a virus serologically related to SIVmnd has been reported from Cameroon, suggesting that mandrills may represent a viral reservoir for human. To confirm this hypothesis, further seroepidemiological survey of human samples using SIVmnd peptide would be needed.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 51.06PO - Poster
Attachment, Receptors, Co-Receptors, Entry, Tropism
292 GENETIC POLYMORPHISMS OF CCR5 GENE AND CELL SURFACE EXPRESSION OF CCR5 MOLECULES IN HIV-1 HIGHLY EXPOSED PERSISTENTLY SERONEGATIVE (HEPS)
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 292)
T Samleerat1, S Dettrirat2, W Kunachiwa2 and P Leechanachai1
Most individuals exposed to HIV-1 have a high change to become infected. However, some individuals in high-risk groups are resistant to infection and remain HIV seronegative despite multiple repeated exposures to the virus.
293 EXPRESSION OF CD4 ON HUMAN PERIPHERAL BLOOD NEUTROPHILS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 293)
P Biswas1, B Mantelli1, A Sica2, M Malnati1, C Panzeri1, A Saccani2, H Hasson1, A Vecchi1, A Saniabadi3, P Lusso1, A Lazzarin1 and A Beretta1
CD4, the HIV entry receptor, is known to be expressed on T cells and monocytes/macrophages. However, it has been reported also in normal CD34+ progenitor cells, in a subset of eosinophils and basophils, in in vitro HHV6-infected CD8+, NK, δγ T lymphocytes and recently also in NK lymphocytes.
294 IN HUMAN FETAL ASTROCYTES, HIV-1 PENETRATES AND INTEGRATES THROUGH CCR5-MEDIATED ENDOCYTOSIS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 294)
K Deiva, C Hery, P Leclerc, B Gubler and M Tardieu
CCR5-mediated endocytosis is an active pathway for virions uptake in astrocytes, which results in a viral integration.
295 EARLY POST-FUSION EVENTS IN THE REPLICATION OF HIV-2
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 295)
C Schmitz1, D Marchant1, S Reuter2, K Aubin1, MT Dittmar2 and A McKnight1
Both the gag and env genes encoded within the HIV-2 genome allow it to reach an appropriate cellular compartment after fusion at the cell membrane.
296 INFLUENCE OF THE V3 CHARGE IN CONJUNCTION WITH GP120 N-LINKED GLYCOSYLATION PATTERN ON HIV-1 PHENOTYPIC PROPERTIES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 296)
A Nabatov, G Pollakis, T Linnemann, A Kliphius, M Chalaby, and W Paxton
We generated and studied a panel of HIV-1 molecular cloned viruses altering in their V3 charge and N-linked glycosylation patterns. The generated viruses reflected intra-patient evolution determined from one individual from the Amsterdam Cohorts Studies who progressed in their HIV-1 disease course.
297 DISTRIBUTION OF CCR5-DELTA32, CCR2-64I AND SDF1-3′A POLYMORPHISMS IN THREE DIFFERENT ETHNIC GROUPS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 297)
RS Grimaldi1,2, AX Acosta1,3, J Spinola1, MC Argollo1 and B Galvao-Castro1,2
These findings together with others host genotypes related to the HIV and AIDS could be an important contribution for better strategies in HIV/AIDS prevention and treatment.
298 ENTRY OF HIV IN PERMISSIVE CELLS IS ASSOCIATED WITH THE FORMATION OF TRITONINSOLUBLE COMPLEXES CONTAINING VIRAL PROTEINS AND NEWLY SYNTHESIZED HIV DNA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 298)
B Krust and AG Hovanessian
Lipid rafts appear to play an important role in the HIV infectious cycle as they are implicated in the HIV entry as well as during assembly of viral proteins and even budding of virus particles. Consequently, the HIV particle membrane has been reported to express lipid raft components and as well as some other cellular proteins.
299 ENDOCYTOSIS OF HIV-1 LEADS TO INFECTION IN TROPHOBLASTS: A STUDY OF HIV-1’s CELLULAR LOCALIZATION AND MECHANISM OF ENTRY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 299)
G Vidricaire, MR Tardif and MJ Tremblay
HIV-1 enters trophoblasts mainly by endocytosis. The presence of high concentrations of viruses in the vesicular fraction may lead to transcytosis of HIV-1 thus accounting for the reported low productive HIV-1 infection in these cells. However, infection also occurs following endocytosis of HIV-1. This constitutes a novel entry route leading to infection by HIV-1.
300 SYNDECANS AS HIV ATTACHMENT RECEPTORS MODULATE HIV PATHOGENESIS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 300)
P Gallay1, M Bobardt1, A Saphire1, A Parseval1, J Elder1 and G David2
We found that syndecans expressed on specific cell types or tissues play distinct but critical roles in HIV pathogenesis. First, we found that syndecans expressed together (in cis) with entry receptors CD4 and CCR5 on macrophages greatly enhance HIV infection by promoting viral adsorption. Given that CD4 and CCR5 are weakly expressed on macrophages, HIV uses syndecans as attachment receptors to compensate for low levels of entry receptors. More recently, we demonstrated that syndecans also serve as in trans attachment receptors for HIV. Specifically, we found that syndecans expressed on the surface of ‘nonpermissive’ cells (which do not express CD4 and CCR5) not only capture HIV but present and transmit viruses to ‘permissive’ T cells (which express entry receptors). Importantly, syndecans capture HIV primary isolates derived from physiological peripheral blood mononuclear cells suggesting that HIV-syndecan interactions occur in vivo. Furthermore, we showed that syndecans preserve virus infectivity for a week, whereas unbound virus loses its infectivity in less than a day. We obtained evidence that the V3 loop of gp120 serves as the main viral binding site for syndecans. Thus, HIV exploits syndecans as in cis and in trans attachment receptors to modulate its replication in the host.
301 POLYMORPHISMS OF CCR5 GENE AND ITS REGULATORY REGION IN HIV-1 HIGHLY EXPOSED PERSISTENTLY SERONEGATIVE (HEPS) GROUP
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 301)
P Leechanachai1, T Samleerat1, S Dechtrirat2 and W Kunachiwa2
This study provides an evidence for the association between the CCR5 59029G/G and 59353T/T haplotype in the absence of Δ and -m303 and resistant to HIV-1 infection in the HEPS individuals.
302 HIV-1 CO-RECEPTOR USE DURING HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART)
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 302)
I Karlsson1, E Vincic1, U Karlsson1, L Antonsson2, C Owman2, A Karlsson3, B Ljungberg1 and EM Fenyö1
HAART changes evolution of HIV-1 biological phenotype. Virus with R5 phenotype reappears or is maintained in most of the cases.
303 INHIBITION OF CD8+ T-CELL APOPTOSIS BY AMD3100
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 303)
AZ Decrion1, C Deng2, JM Estavoyer3, WA O’Brien2 and G Herbein1
All together our data suggest that AMD3100 inhibits CD8+ T cell apoptosis via at least two distinct mechanisms: blockade of SI virus binding to CXCR4 and decreased immune activation.
304 INCREASE IN CD4+ T-CELL SURFACE CXCR4 DENSITY AS A CAUSE OF EMERGENCE OF HIV-1 X4 STRAINS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 304)
YL Lin1, P Portales2, M Segondy3, C Mettling1, V Baillat4, C Merle de Boever4, V Lemoing4, B Réant1,2, C Garcia2, J Clot2, J Reynes4 and P Corbeau1,2
The factors determining the emergence of X4 isolates in some HIV-1-infected subjects with late-stage disease, which has been correlated with a poor prognosis, are unknown.
305 DC-SIGN FROM AFRICAN GREEN MONKEYS IS AN EFFICIENT ATTACHMENT FACTOR FOR SIVagm
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 305)
MJY Ploquin1, OM Diop2, N Sol-Foulon3, L Mortara1,4, A Faye2, MA Soares1,5, Y Van Kooyk6, A Amara7,8, O Schwartz3, F Barré-Sinoussi1 and MC Müller-Trutwin1
This is the first time that the virological functions of DC-SIGN from a natural host species of SIV have been analysed. This study reveals the ability of DC-SIGNagm to promote infection. Thus the low LN viral loads in AGM are not due to a non-functional DC-SIGNagm.
306 STRUCTURAL ASPECTS ON THE INTERACTIONS BETWEEN HIV-1 GP120 AND CO-RECEPTORS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 306)
F Veas, A Mechulam, M Pugniere, J Gajardo, D Misse, F Roques and M Cerutti
Our results concerning the determination of the involved residues and structure of gp120 in the interaction with CCR5 and the consequences will be exposed and discussed. This research was supported by ANRS, CNRS, IRD. AM and JG are, respectively, ANRS and IRD PhD fellows.
307 307HIV CO-RECEPTOR UTILIZATION INVOLVES CONSERVED V3 DOMAINS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 307)
P Suphaphiphat1, SY Chang2, S Teeravechyan1, A Thitithanyanont3, S Paca-Uccaralertkun3, M Essex1 and TH Lee1
The current model for human immunodeficiency virus type 1 (HIV-1) co-receptor binding proposes that the variable V3 loop of gp120 dictates co-receptor choice, and the bridging sheet residues contribute to binding contacts with the co-receptor. The highly conserved nature of the bridging sheet residues is thought to provide some molecular basis for the observed functional convergence in CCR5 usage by primary non-syncytium-inducing (NSI) viruses.
308 A SYNDECAN-4/CXCR4 COMPLEX MODULATES STROMAL CELL DERIVED FACTOR-1α BINDING TO CXCR4 ON HUMAN PRIMARY LYMPHOCYTES AND MACROPHAGES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 308)
L Gattegno1,3, M Hamon1, E Mbemba1, N Charnaux1,3, H Slimani1, L Saffar1, R Vassy2 and A Starzec2
This study investigates the involvement of proteoglycans in stromal cell derived factor-α (SDF-α) binding to HeLa cells, and to human primary lymphocytes and macrophages. We show that CXC chemokine, SDF-α binds to high and low affinity sites on HeLa cells, primary human lymphocytes and monocyte derived-macrophages.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 51.07PO - Poster
Reverse Transcription
309 MECHANISM OF GENETIC RECOMBINATION IN HIV: ROLE OF THE STRUCTURE OF THE GENOMIC RNA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 309)
A Moumen, R Galetto, V Giacomoni-Fernandes, L Polomack, M Véron, H Buc and M Negroni
The frequent occurrence of recombination among divergent HIV genomes is well documented. Recombination is the consequence of template switching by the reverse transcriptase from one to the other of the two copies of genomic RNAs present in each viral particle. The understanding of the mechanism leading to such a switch has been the object of intensive studies in the last decade.
310 DNA FLAP MUTANT HIV-1 VIRUSES ARE DEFECTIVE IN THE MATURATION OF REVERSE TRANSCRIPTION COMPLEX INTO PRE-INTEGRATION COMPLEX, AND IN NUCLEAR TRANSLOCATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 310)
N Arhel, P Souque, MC Prévost and P Charneau
Central initiation and termination of HIV-1 reverse transcription, mediated by two additional cis-acting sequences, central polypurine tract (cPPT) and termination sequence (CTS), leads to the synthesis of a DNA flap motif.
311 DNA BINDING FUNCTION AND POLYMERASE ACTIVITY OF THE p51 SUBUNIT OF HIV-1 RT ARE STIMULATED IN THE PRESENCE OF 15 KDa RNase FRAGMENT
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 311)
V Pandey and A Upadhyay
The p51 subunit of HIV-1 RT exists as a monomer and is catalytically inactive. We observed that polymerase activity of p51 is significantly stimulated when supplemented with RNase H fragment. Similarly, RNA cleavage activity of the inactive RNAse H fragment is partially restored in the presence of p51.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 51.08PO - Poster
Integration
312 MECHANISMS OF HIV-1 NUCLEARIZATION IN MITOTIC CELLS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 312)
A Mannioui, C Schiffer, N Felix, E Le Rouzic, E Nelson, A Brussel, C Petit, S Benichou, P Sonigo, JC Gluckman and B Canque
Surprisingly, infection with a .ΔVpr mutant of cells that were blocked in G1/S transition or relaxed, failed to reveal any significant nuclearization defect. In contrast, isogenic .ΔNLS MA mutants (K26IK27I) displayed fourfold reduced capacity to form integrated provirus in G1/S blocked cells. The mechanisms responsible for these observations are currently under investigation.
313 CRITICAL ROLE OF LEUCINE 172 OF HIV-1 INTEGRASE FOR BOTH INTEGRATION OF PROVIRAL DNA AND UNG2 PACKAGING PROCESSES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 313)
S Priet, JM Navarro, N Gros, G Quérat and J Sire
Results showed that no integrated proviral L172A genome was detectable, in contrast to wild-type viruses. Finally, complementation experiments of L172A viruses by supplying in trans Vpr-L172A IN fusion protein resulted in the rescue of L172A virus infectivity. These data suggest that a significant increase in amounts of L172A IN in viral particles was sufficient to promote proviral DNA integration events.
314 SPECTROSCOPIC STUDIES OF DKA-METAL INTERACTIONS: A MODEL FOR THE MEASURE OF THE INTERMETALLIC DISTANCE IN THE HIV-1 INTEGRASE ACTIVE SITE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 314)
C Maurin1, F Bailly1, E Buisine1, H Vezin1, G Mbemba2, JF Mouscadet2 and P Cotelle1
HIV-1 integrase (IN) is the HIV third enzyme and constitutes, therefore, an attractive target for anti-AIDS therapy. IN is a 32 kDa protein composed of three domains. The central catalytic domain (residues 50.212) contains a triad of invariant carboxylate residues, D64, D116 and E152, which are required for catalysis.
315 INHIBITION OF RECOMBINANT HUMAN IMMUNODEFICIENCY VIRUS’s INTEGRASE BY NATURAL TRITERPENE DERIVATIVES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 315)
EA Semenova1, OA Plyasunova1, NI Petrenko2, VZ Petukhova2, EE Shults2, GA Tolstikov2 and AG Pokrovsky1
Integration of human immunodeficiency virus (HIV) DNA into the human genome requires the virus-encoded integrase (IN) protein, and, therefore, the IN is a suitable target for antiviral strategies.
315A DO RETROVIRUSES PREFERENTIALLY INTEGRATE WITHIN HIGHLY PLASTIC REGIONS OF THE HUMAN GENOME?
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 315A)
P Rossignol1, V Mimaud1, E Guinet1, L Benboudjema1, C Jasmin2, MG Tovey1 and MC Lang1,3
The chromosomal region 22q11 is remarkable for its high plasticity involving DNA double strand breaks. These chromosomal break points may lead to translocations, large deletions, and immunoglobulin rearrangements, frequently observed in this chromosomal band. We propose that provirus integration preferentially occurs in these plastic regions of the genome, and that the subsequent insertional mutagenesis leads to the present observations. Finally, we indicate the possibility that the small size of chromosome 22 is associated with this physical property of the genome.
315B MECHANISM OF HIV-1 INTEGRASE INHIBITION BY STYRYLQUINOLINE COMPOUNDS IN VITRO
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 315B)
E Deprez, M Kolaski, M Le Bret, JF Mouscadet and JC Brochon
Our results suggest that two inhibitor binding modes exist: the first one prevents the viral DNA-binding and then the two subsequent reactions, i.e., the 3'-processing and the strand transfer, the second one prevents the target DNA-binding in inhibiting the strand transfer.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 51.09PO - Poster
Regulation of HIV Transcription
316 HIV-1 NEF INTERACTS WITH EUKARYOTIC RIBOSOMAL PROTEIN
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 316)
I Dichamp1, W Chen1, U Mahlknecht2 and G Herbein1
The Nef protein plays important roles in HIV replication and interacts with different transcription factors, but little is known about the function of Nef in the eukaryotic translation.
317 HETEROLOGOUS EXCHANGE OF SIV PROMOTER ELEMENTS AS A NOVEL MEANS OF ATTENUATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 317)
P Sommer, JP Vartanian, M Henry, D Guetard and S Wain-Hobson
After integration into the host cell genome, lentiviral gene expression is controlled by promoter elements located in the U3 region of the 5' long terminal repeat (LTR). The importance of the various transcriptional control elements has been extensively studied and revealed a surprising redundancy, which allows the interaction with multiple transcription factors, thereby ensuring viral replication in a variety of cellular conditions.
318 P-TEFB PHOSPHORYLATES RD AND DISSOCIATES NEGATIVE EFFECTORS FROM TAR
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 318)
K Fujinaga1 and B Matija Peterlin2
The elongation of transcription is a highly regulated process that requires negative and positive effectors.
319 NOVEL TRANSLATIONAL CONTROL OF HIV-1 env mRNA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 319)
DFJ Purcell, JL Howard, A Johnson and JL Anderson
A novel translation mechanism such as a cap-dependent ribosome shunting or cap-independent internal ribosome entry site (IRES) mechanism supports the translation of Env. The Vpu expression from the same env mRNAs follows the leaky ribosome scanning model. Therefore, HIV-1 env mRNAs represent an unusual example where two overlapping ORFs are translated via independent mechanisms. Resolving this novel translational control will reveal unique RNA targets for therapeutic intervention.
320 MECHANISM OF TAT-MEDIATED TRANSACTIVATION OF THE HIV-1 PROMOTER
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 320)
RE Kiernan1, V Brès1, LK Linares2, O Plechakova3, C Tréand4, S Emiliani4, KT Jeang5, O Coux3, M Scheffner2 and M Benkirane1
An understanding of how Tat interacts with its co-activators is crucial to the elucidation of Tat function. We will discuss the role of Tat’s post-translational modifications in the regulation of its transcriptional function.
321 THE DESTABILIZING ACTIVITY OF HIV-1 NUCLEOCAPSID PROTEIN ON THE SECONDARY STRUCTURE OF cTAR DNA IS CRITICALLY DEPENDENT ON THE TERMINAL BULGES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 321)
H Beltz1, J Azoulay1, S Bernacchi1, JP Clamme1, D Ficheux2, B Roques3, JL Darlix4 and Y Mely1
The nucleocapsid protein NCp7 of HIV-1 possesses nucleic acid chaperone properties that are critical for the obligatory strand transfer reactions required for the synthesis of a complete proviral DNA by reverse transcriptase.
322 IL-8 AND MCP-1 REGULATE IL-6 INDUCED HIV-1 EXPRESSION IN CHRONICALLY INFECTED CELLS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 322)
L Adduce1, C Rizzi1, G Poli1,2 and M Alfano1
In chronically infected U1 cells, IL-6 did not activate transcription factors directly involved in the regulation of HIV-1 LTR, but induced expression of both IL-8 and MCP-1. Neutralization of these AP-1 regulated cytokines drastically reduced IL-6-induced HIV expression. Therefore, pro-HIV effect of IL-6 is indirect and mediated by IL-8 and MCP-1, a phenomenon similar to that observed in IL-2-stimulated PBMC. Moreover, this study underline the importance of IL-6 in the deveolpment of AIDS as well as to the onset of AIDS-associated pathologies, i.e., Kaposi’s sarcoma and dementia, regulated by IL-8 and MCP-1, respectively.
323 ROLE OF THE SWI/SNF CHROMATIN REMODELLING COMPLEX IN TAT-MEDIATED TRANSACTIVATION OF THE HIV-1 PROMOTER
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 323)
C Tréand1, V Bres2, R Kiernan2, R Benarous1, V Ogrysko3, M Benkirane2 and S Emiliani1
The human immunodeficiency virus type 1 (HIV-1) trans-activator protein (Tat) stimulates transcription from the viral long terminal repeats (LTR) via a RNA target termed TAR.
324 MOLECULAR MECHANISM OF HIV-1 NUCLEOCAPSID PROTEIN CHAPERONE ACTIVITY DURING REVERSE TRANSCRIPTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 324)
Y Mély1, S Bernacchi1, J Azoulay1, JP Clamme1, B Roques2 and JL Darlix3
The nucleocapsid protein, NCp7, of HIV-1 possesses a nucleic acid chaperone activity that is critical in minus and plus strand transfer during reverse transcription. The minus strand transfer notably relies on the ability of NCp7 to destabilize the stable stem of both the TAR sequence at the 3' end of the viral genome and the complementary sequence, cTAR, in minus strong-stop DNA.
325 STRUCTURAL ROLE OF THE FIRST ZINC KNUCKLE OF THE HIV-1 NCp7 INVESTIGATED BY NMR AND BIOCHEMICAL STUDIES OF THE CYS28-HIS MUTANT
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 325)
S Ramboarina2, S Druillennec1, N Morellet1, S Bouaziz1 and BP Roques1
The nucleocapsid protein NCp7 of HIV-1 is a metalloprotein characterized by two CX2CX4HX4C motifs that plays a key role in the retroviral replication cycle.
326*
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 326)


327 EXOGENOUS HIV-1 VPR PROTEIN ACTIVATES NF-κB, AP-1 AND JNK IN PROMONOCYTIC AND LYMPHOID CELLS: ROLE IN AIDS PATHOGENESIS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 327)
A Varin1, AZ Decrion1, BP Roques2, BB Aggarwal3 and G Herbein1
Overall our results suggest a critical role for exogenous Vpr in AIDS pathogenesis via stimulation of HIV-1 provirus present in cellular reservoirs.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 51.10PO - Poster
Maturation, Morphogenesis and Assembly
328 ROLE OF GAG-POL IN ANNEALING OF tRNALys3 TO HIV-1 GENOMIC RNA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 328)
J Saadatmand, S Cen and L Kleiman
In addition to the previous well-documented role of Gag and mature nucleocapsid in annealing, these results indicate additional roles for Gag-Pol in the tRNALys annealing process.
329 AN ENHANCED PKR ANTIVIRAL RESPONSE IN ASTROCYTES DRAMATICALLY RESTRICTS PRODUCTIVE HIV-1 EXPRESSION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 329)
CL Ong1, JC Thorpe1, PR Gorry1, S Bannwarth2, A Mouland2, A Gatignol2 and DFJ Purcell1
A readily activated PKR antiviral response in astrocytes contributes to their restricted expression of HIV-1 structural proteins and progeny virion. Low endogeneous expression of TRBP accounts for the enhanced PKR response in astrocytes. Augmenting the PKR response pathway in cells productively infected by HIV-1, such as CD4+ T cells, may duplicate the non-productive infection phenotype of astrocytes. Decreasing cellular levels of TRBP in HIV-infected cells may be an effective strategy to increase this innate antiviral pathway.
330 A NOVEL ROLE FOR RESIDUES WITHIN THE p2 REGION OF HIV-1 GAG IN VIRAL RNA PACKAGING SPECIFICITY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 330)
RS Russell, B Spira, C Liang and MA Wainberg
HIV-1 encapsidates two copies of viral genomic RNA in the form of a dimer, linked in parallel at the 5' ends. The most characterized RNA sequence involved in the dimerization process is a stem-loop structure (SL1), known as the dimerization initiation site (DIS). Our previous work showed that partial deletion of SL1 caused decreased viral replication capacity, but these defects were largely corrected by a series of compensatory point mutations (CMs) in the viral peptide 2 (p2), nucleocapsid, matrix and capsid proteins.
331 THE TYROSINE KINASE HCK INHIBITS THE EXTRACELLULAR RELEASE OF HIV-1 GAG PSEUDOPARTICLES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 331)
R Vigne, M Douaisi, G Bessou, M Courcoul, Y Savon, S Dussart and E Decroly
We have previously shown that the tyrosine kinase Hck is an inhibitor of HIV-1 replication counteracted by the viral Vif protein. In viral production assays, we observed that Hck inhibits strongly the release of HIV-1 virions from transfected human cells, in absence of Vif. Previous works indicated also that Gag could be phosphorylated on tyrosine. Therefore, we hypothesized that Gag could interact directly with Hck and that this interaction may be negative for HIV-1 replication, independently of Vif.
332 HELICAL STRUCTURE DETERMINED BY NMR OF THE HIV-1 (345-392) GAG, ENCOMPASSING THE C-TERMINAL DOMAIN OF CAPSID, p2, AND THE N-TERMINAL SEQUENCE OF NCp7: IMPLICATIONS FOR PARTICLES ASSEMBLY, VIRION MORPHOLOGY AND RNA PACKAGING
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 332)
N Morellet, S Druillennec, C Lenoir, S Bouaziz and BP Roques
HIV-1 assembly is initiated by polymerization of the Gag polyprotein to form a spherical shell closely apposed to the inner membrane of budding particles. In Gag, p2 is located between the capsid (CA) and the nucleocapsid protein (NCp7). Genetics analyses have shown that p2 has a critical role in virus particle assembly.
333 EFFECTS OF INTERFERENCE RNA SPECIFIC FOR HUMAN LysRS UPON tRNALys INCORPORATION, ANNEALING AND VIRAL INFECTIVITY IN HIV-1
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 333)
F Guo, S Cen, M Niu, H Javanbakht and L Kleiman
The major human tRNALys isoacceptors, tRNALys1,2 and tRNALys3, are selectively packaged into HIV-1 during assembly, where tRNALys3 acts as a primer for reverse transcription. Lysyl-tRNA sythetase (LysRS) is incorporated into HIV-1, independently of tRNALys, via its interaction with gag, and is a strong candidate for being the signal that specifically targets tRNALys for viral incorporation.
334 THE ROLE OF HUMAN LYSYL-tRNA SYNTHETASE IN tRNALys PACKAGING AND GENOMIC PLACEMENT INTO HIV-1
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 334)
S Cen and L Kleiman
During HIV-1 assembly, the major human tRNALys isoacceptors, tRNALys1,2 and tRNALys3, are selectively packaged into the viruses. However, only tRNALys3 is placed onto the primer binding site on the viral RNA genome, where it acts as a primer for reverse transcription.
335 HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 CHIMERIC GAG PROTEIN CARRYING AN ACTIVE PROTEASE DOMAIN IN THE MATRIX REGION IS EFFICIENTLY INCORPORATED BUT SEVERELY DEFECTIVE IN THE PROCESSING OF GAG PARTICLES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 335)
CT Wang1,2, SW Chen1,2, HC Chiu1,2, WH Liao1,2 and FD Wang3
Our data strongly suggest that positioning an active HIV PR in the matrix region has no major effects on the chimeric PR incorporation, but significantly affects the PR-mediated virus particle maturation.
336 RETROVIRAL GENOMIC RNAs ARE TRANSPORTED TO THE PLASMA MEMBRANE BY ENDOSOMAL VESICLES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 336)
E Basyuk, T Galli, M Mougel, JM Blanchard, M Sitbon and E Bertrand
The viral genomes of alpha- and gamma-retroviruses follow a yet unidentified outbound route before assembling with the budding particle at the plasma membrane. Using single molecule detection of genomic RNA in living cells, we show here that murine leukaemia virus RNAs are transported on both lysosomes and transferrin-positive endosomal vesicles. This process requires both Gag and Env polyproteins.
337 HIV-1 GAG PROCESSING IS NOT SUFFICIENT FOR VIRUS INFECTIVITY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 337)
A Bukrinskaya, M Sharkey and M Stevenson
Our results demonstrate that infected and transfected cells produce ‘early’ noninfectious virus of an unusual core morphology. We suggest that the process of virus maturation is dependent not only on the Gag precursor cleavage but on other factors that participate in core maturation.
338 THE INTERACTION BETWEEN HIV-1 GAG AND HUMAN LYSYL-tRNA-SYNTHETASE DURING VIRAL ASSEMBLY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 338)
H Javanbakht1,2 and L Kleiman1,3
Based on these studies, we conclude that the Gag/LysRS interaction depends on Gag sequences within the C-terminal domain of capsid sequences (last 54 amino acids) and amino acids 208–259 of LysRS. The latter domain includes the class II aminoacyl-tRNA synthetase consensus sequence known as motif 1. Both regions have been implicated in homodimerization of capsid and LysRS, respectively. Sequences falling outside these amino acid stretches can be deleted from either molecule without affecting the Gag/LysRS interaction, further supporting the observation that LysRS is incorporated into Gag virallike particles independently of its ability to bind tRNALys.
339 A CYTOPLASMIC DOMAIN FUSION PROTEIN OF THE TRANSMEMBRANE GLYCOPROTEIN gp41 CONFERS DOMINANT INTERFERENCE WITH HUMAN IMMUNODEFICIENCY TYPE 1 VIRUS INFECTIVITY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 339)
S Chen and W Chan
The cytoplasmic domain of the human immunodeficiency type 1 virus (HIV-1) transmembrane envelope (Env) glycoprotein gp41 was determined to interact with the viral matrix (MA) protein during virus assembly/budding. In addition, we have shown that the cytoplasmic domain of gp41 possesses the potential to self-assemble into a highordered multimeric structure and to interact with cellular membranes.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 51.11PO - Poster
Viral Accessory Genes
340 INHIBITION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 2 REPLICATION DUE TO HIV-2 VIF MUTANTS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 340)
AC Ribeiro1,2, J Gonçalves1 and I Barahona1,2
Virion infectivity factor (VIF) is one of the HIV accessory proteins and is conserved in the primate lentivirus groups. In the absence of vif gene, HIV-1 and HIV-2 infection of non-permissive cells, like PBMCs, produce no virion. This protein is, therefore, a new potential target for retroviral strategy. VIF function is still controversial and resulted from studies with HIV-1.
341 FUNCTIONAL ANALYSIS OF THE INTERACTION BETWEEN VPR HIV-1 AND THE NUCLEOPORIN hCG1
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 341)
E Le Rouzic1, R Villet1, A Mousnier2, C Dargemont2 and S Benichou1
These results indicate that mutations, that affect the binding with hCG1, also disturb the accumulation of Vpr at the nuclear envelope. Such Vpr mutants will represent valuable tools to study the role of the association with the nucleoporin hCG1 in the contribution of Vpr to promote the nuclear import of the viral DNA.
342 HIV-1 TAT PROTEIN INDUCES INTERLEUKIN-10 IN HUMAN MONOCYTES: IMPLICATION OF PKC AND NFκB
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 342)
Y Bennasser, X Contreras, N Chazal and E Bahraoui
HIV-1 infection is associated with two major disorders: immunological dysfunctions as early as the asymptomatic stage and T CD4 depletion at late stage. PBMC of HIV-1-infected patients produce high levels of interleukin-10 (IL-10), a highly immunosuppressive cytokine, paralleling the progressive loss of T helper function as the infection progresses toward AIDS. In this study, we show that HIV-1 Tat protein, by acting at the cell membrane level induces IL-10 production by human peripheral blood monocytes of healthy donors.
343 HIV-1 NEF INDUCES A GENERAL ALTERATION OF THE EARLY/RECYCLING ENDOCYTIC COMPARTMENTS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 343)
R Madrid1, K Janvier1, D Hitchin2, I Kim1, B Hoflack4, J Guatelli2,3 and S Benichou1
The HIV-1 Nef protein perturbs the trafficking of transmembrane proteins such as CD4 by interacting with the clathrin-associated adaptor protein (AP) complexes involved in vesicular transport throughout the endocytic pathway. We previously reported that Nef induces an expansion of endosomal structures and specifically stabilizes the association of type 1 and 3 AP complexes to these structures.
344 THE VIF PROTEIN OF HIV-1 INTERACTS WITH THE WW2 AND WW3 DOMAINS PRESENT IN THE HECT E3 UBIQUITIN LIGASES OF THE NEDD4 FAMILY AND IS SENSITIVE TO UBIQUITINATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 344)
S Dussart, M Courcoul, G Bessou, M Douaisi, R Vigne and E Decroly
The viral infectivity factor (Vif), one of the six auxiliary genes expressed by HIV-1, is required for productive infection in primary CD4-positive T lymphocytes and macrophages. It has been described that Vif is needed to overcome antiviral factors like the cytidine deaminase CEM15 allowing viral replication in primary cells. To understand the mechanisms of action of Vif, it is important to identify new cellular factors interacting with Vif.
345 DIRECTED EXPRESSION OF THE HIV-1 ACCESSORY PROTEIN VPU IN DROSOPHILA FAT BODY CELLS INHIBITS TOLL-DEPENDENT IMMUNE RESPONSES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 345)
F Leulier2, C Marchal1, I Miletich2, B Limbourg-Bouchon2, B Lemaitre2 and R Benarous1
Given the conservation of the Toll/NF-κB signalling pathways of innate immunity between flies and mammals, our results suggest a function for Vpu in the inhibition of host NF-κB mediated innate immune defences and provide a powerful genetic approach for studying Vpu-inhibition of NF-κB signalling in vivo.
346 ENHANCED CD4 DOWN-MODULATION BY LATE-STAGE HIV-1 NEF ALLELES IS ASSOCIATED WITH INCREASED ENV INCORPORATION AND VIRAL REPLICATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 346)
J Lama1,2, E Argañaraz1, M Schindler3 and F Kirchhoff3
Three viral proteins participate in the down-modulation of CD4 in HIV-1-infected cells. The underlying mechanisms have been extensively investigated. However, the physiological relevance of this phenomenon remains poorly understood. To address the role of CD4 down-modulation in HIV-1 pathogenesis in vivo, we have characterized the functional properties of nef alleles isolated from seven HIV-1-infected patients at either the stage of AIDS (late alleles) or during the asymptomatic phase of infection (early alleles).
347 NEF-INDUCED CD4 DOWN-REGULATION: ROLES OF RAFT AND PALMITOYLATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 347)
N Sol-Foulon1, C Esnault1, Y Percherancier2, P Cunha1, F Bachelerie2 and O Schwartz1
Many viral and cellular proteins are modified by fatty acid acylation with palmitate or myristate. Protein palmitoylation may be essential for plasma membrane association and lipid raft targeting. Regarding CD4, both palmitoylation and association with Lck contribute to enrichment in rafts. HIV-1 Nef is myristoylated and partly associated with rafts. We have addressed whether Nef affects CD4 association with rafts and palmitoylation, and whether Nef association with rafts influences its down-modulating activity.
348 THE TAT SPECIFIC HIV-1 SPLICING SITE A3 IS SUBJECTED TO A TIGHT REGULATION BY SEVERAL CELLULAR PROTEINS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 348)
H Hallay1, L Ayadi1, D Ropers1, S Jacquenet1, A Méreau1, CM Stoltzfus2, R Gattoni3, J Stévenin3 and C Branlant1
Production of numerous proteins by virus HIV-1 is based on the alternative splicing of its primary transcript. In the central part of HIV-1 RNA, five splicing acceptor sites are in competition: A3, A4a, b and c, and A5. A3 and A5 utilization are required for tat and nef mRNA production, respectively, whereas one of the A4a,b and c sites has to be used to produce rev mRNA. We demonstrated the existence of a complex regulation at the A3 site.
349 DIFFERENTIAL EFFECTS OF THE SR PROTEINS ON THE UTILIZATION OF THE A1 TO A5 SPLICING SITES OF HIV-1 RNA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 349)
L Ayadi1, D Ropers1, R Gattoni2, S Jacquenet1, L Damier1, J Stévenin2 and C Branlant1
Splicing is a crucial step for HIV-1 virus multiplication. Eight HIV-1 acceptor sites are used in competition to produce the Vif, Vpu, Vpr, Nef, Env, Tat and Rev mRNAs. Although SR proteins are known to modulate alternative splicing of pre-messenger RNAs, effects of SR proteins on utilization of the A1 to A5 HIV-1 acceptor sites had not been investigated. To test this effect, we determined the in vitro splicing efficiencies of transcripts containing one or several HIV-1 acceptor sites, in S100 extract or mixtures of S100 and nuclear extracts, in the presence or absence of recombinant SR proteins (ASF/SF2, SC35, 9G8 or SRp40).
350 DIMINUTION OF HUMAN IMMUNODEFICIENCY VIRUS NEF STABILITY REDUCES VIRUS INFECTIVITY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 350)
C Bertsch, D Cluet, C Beyer, L Gloeckler, A Cecile, B Lafont, JP Gut and AM Aubertin
The nef gene of human and simian immunodeficiency viruses codes for a membrane-associated protein critical for AIDS development. In this report, we determine the impact of a single point mutation Dl86N in the βD sheet of HIV-1 Nef Lai on Nef characteristics, its stability, and the consequences on virus particles infectiousness. Using mammalian expression plasmids, we demonstrated that the presence of the D186N mutation is responsible for a reduction of Nef half-life.
351 SAM68 AND REV/RRE FUNCTION: IS SAM68 A GOOD TARGET FOR HIV THERAPIES?
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 351)
L Jin1, JH Coyle1, YC Bor1, J Swartz1, SJ Taylor2, D Rekosh1 and ML Hammarskjold1
Sam68, a member of the STAR protein family, has been proposed to function as a cellular Rev equivalent. Previous studies have indicated that a C-terminally deleted form (SamΔ) inhibits Rev function and HIV replication. It was suggested that SamΔ is a specific transdominant-negative inhibitor of Sam68 function and might be developed for HIV therapy.
352 HIV-1 NEF ENHANCES THE MEMBRANE EXPRESSION AND VIRION INCORPORATION OF ENV PRODUCTS: A MODEL FOR THE NEF-DEPENDENT INCREASE OF HIV-1 INFECTIVITY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 352)
M Federico1, I Schiavoni1, S Trapp2, AC Santarcangelo1, K Pugliese1 and AS Baur2
The expression of HIV/SIV Nef increases the viral infectivity through mechanisms not fully elucidated yet. We found that viral particles emerging from cells expressing Δnef HIV-1 were neutralized with far lower concentrations of either anti Env gp41 antibodies, or recombinant soluble human CD4, with respect to wild-type HIV-1 virions. This coupled with decreased incorporation of both gp41 and gp120 Env products in viral particles, and with reduced steady-state levels of cell membrane associated Env products.
353 STRUCTURAL STUDIES OF THE INTERACTION BETWEEN VPR, AN HIV-1 REGULATORY PROTEIN, AND OLIGONUCLEOTIDES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 353)
S Bourbigot, S Druillennec, N Morellet, S Bouaziz and BP Roques
Vpr is a 14 kDa HIV-1 regulatory protein, participating to the preintegration complex (PIC). It is mostly found in the nucleus and seems to be involved in the proviral DNA import into the host cells. Vpr is able to interact with many partners and forms very stable complexes with nucleic acids. Therefore, we focused on the structure of Vpr interacting with an oligonucleotide.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 51.12PO - Poster
Biology of Transmission
354 CYTOKINE AND CHEMOKINE PROFILES EXPRESSED BY PLACENTAL EXPLANTS FROM HIV-1– AND HIV-1+ WOMEN: ROLE IN THE CONTROL OF HIV MOTHER-TO-CHILD TRANSMISSION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 354)
M Derrien1, A Faye1,2, G Dolcini1, J Maldonado2, G Chaouat2, F Barré-Sinoussi1 and E Menu1,2, the HIV PMTCT PlaNet
Altogether, our results demonstrate that the placental environment is modulated during HIV infection under antiretroviral treatment and that cytokines regulate the passage of HIV across the trophoblast barrier.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 51.13PO - Poster
Compartments of Viral Spreading
355 SAMPLING OF CERVICOVAGINAL SECRETIONS FOR HIV-1 RNA QUANTITATION: A COMPARATIVE STUDY BETWEEN TWO METHODS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 355)
N Abrescia1, P Martinelli2, M Sansone2, A Busto1, M D’Abbraccio1, M Figoni1, R Viglietti1, G Di Nicuolo3, M De Marco1, E Butrico1, A Maddaloni1 and M Piccirillo1
Few comparative studies to evaluate the various cervicovaginal secretions (CVS) sampling methods for HIV-1 quantitative determinations have been performed. In a perspective study we compared a very used method, the cervicovaginal lavage (CVL) with the direct aspirate of cervical mucous (DACM). We studied 24 HIV-1-positive women with detectable plasma viral load (VL) (13 naïves and 11 HAART-experienced).
356 CHARACTERIZATION OF FULL-LENGTH HIV-1 RNA SEQUENCES IN THE FEMALE GENITAL TRACT AND BLOOD: COMPARTMENTALIZATION AND INTRAPATIENT RECOMBINATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 356)
B Weiser1, S Philpott1, H Burger1, C Tsoukas2, B Foley3, K Anastos4 and C Kitchen5
Globally, 90% of HIV-1 infection is spread by heterosexual transmission and half of infected adults are women. Investigation of HIV-1 infection in women, particularly study of virus in the female genital tract, is critical to develop vaccines, therapeutics and strategies to prevent transmission. Studies have documented compartmentalization of HIV-1 sequences between different reservoirs, but full-length RNA genomes derived from different compartments in the same individual have not previously been examined. Furthermore, HIV-1 in the female genital tract is difficult to cultivate and has yet to be fully characterized.
357 HIV-1 IN GENITAL TRACT AND PLASMA OF WOMEN: COMPARTMENTALIZATION OF SEQUENCES, CO-RECEPTOR USAGE, AND INTRAPATIENT RECOMBINATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 357)
K Sherefa-Kemal1, B Foley2, H Burger1, K Anastos3, H Minkoff4, C Kitchen5, S Philpott1, W Gao3, E Robison3, S Holman4, C Dehner1, S Beck1, W Meyer III6, A Landay7, A Kovacs8, J Bremer7 and B Weiser1
Worldwide, 90% of HIV-1 infections are transmitted heterosexually and half of infected adults are women. To understand HIV-1 pathogenesis and halt its spread, it is critical to study virus in the female genital tract. We performed HIV-1 RNA sequence analyses of gp120 env genes obtained contemporaneously from genital tract and plasma of 12 women exhibiting a broad spectrum of disease.
358 TRANSMISSIBILITY AND DISEASE PROGRESSION OF HIV-1 SUBTYPES IN CUBA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 358)
HM Díaz, AL Lubián, M Blanco, FM Rolo, N Martínez and J Joanes
These results suggest that HIV-1 subtypes in Cuba do not differ in rates of progression to AIDS. However, subtype B has had transmission rates higher than non-subtype B group.
359 GENITAL TRACT LYMPHOCYTE AND VIRAL SHEDDING IN HIV-1 INFECTED WOMEN DURING PREGNANCY AND POSTPARTUM
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 359)
A Bardeguez, J Skurnick, P Palumbo, A Garcia, L Pompeo and T Denny
In this prospective cohort pregnancy was not associated with increased lymphocyte shedding compared to postpartum samples. Plasma CD4 count or use of combination therapy was not associated with shedding either. However, elevated plasma viral load was associated with shedding, and shedders had higher plasma viral load than non-shedders. This study emphasizes the relevance of evaluating strategies that decrease both systemic and genital load in order to decrease perinatal and heterosexual transmission.
360 CNS COMPLICATIONS AND THEIR RELATIONSHIP WITH CD4 COUNT AND VIRAL LOAD IN TREATMENT-NAÏVE HIV/AIDS PATIENTS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 360)
T Tsertsvadze, N Gochitashvili, M Zarandia, L Dzigua and L Abashidze
There is a correlation with increased CSF viral load, low CD4 count in PB and presence and type of CNS complications of HIV infection.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 51.14PO - Poster
Anatomical and Cellular Reservoirs
361 DYNAMICS OF HIV VIRAL LOAD IN SEMEN IN PATIENTS TREATED WITH DIFFERENT THERAPEUTIC APPROACHES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 361)
G Liuzzi, D Zinzi, M Zaccarelli, A Amendola, G D’Offizi, R Bellagamba, V Tozzi, R D’Arrigo, M Capobianchi, P Narciso, CF Perno and A Antinori
Our data suggest that HIV RNA in semen usually follows response to HAART and rebound during HAART interruption. During virological failure HIV RNA in semen may remain detectable suggesting the possibility of sexual transmission of resistant virus with unprotected sex.
362 EVIDENCE OF GENOTYPIC RESISTANCE DIVERSITY OF BOTH ARCHIVED AND CIRCULATING VIRAL QUASISPECIES IN BLOOD AND SEMEN OF HIV-INFECTED MEN WITH MULTIPLE THERAPEUTIC FAILURE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 362)
J Ghosn1,3, JP Viard2, C Katlama3, M de Almeida4, R Tubiana3, L Aaron2, C Goujard5, D Salmon6, M Leruez-Ville1, C Rouzioux1 and ML Chaix1
Resistant HIV strains are frequent (70%) in the semen of heavily pretreated men, with genotypic resistance pattern diversity confirming HIV compartmentalization. Thus, the storage of archived proviruses might differ according to the anatomic reservoir considered. In the issue of sexual transmission, we also show that seminal plasma and semen cells may be differently involved in the spread of HIV transmission.
363 PERSISTENCE OF HIV DNA IN THE CERVIX IS UNRELATED TO HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART) AND NOT ASSOCIATED WITH MUCOSAL CD4+ T LYMPHOCYTE (T CELLS) OR MACROPHAGE/MONOCYTE (MM) DEPLETION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 363)
M Prakash1, S Patterson1, F Gotch1, C Pritchard2 and M Kapembwa3
Viral latency was detected more commonly in CIE MM than PB supporting the concept of cervical mucosa as a separate HIV reservoir. Despite ‘successful’ HAART, CIE remains a potential source of HIV transmission.
364 HUMAN TESTICULAR CELLS AS POTENTIAL HIV RESERVOIRS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 364)
V Roulet1, A Le Tortorec1, H Bruneau1, J Reeves3, A Ruffault2, B Jégou1 and N Dejucq-Rainsford1
It appears that the restriction for HIV-1 strains replication in isolated Leydig cells occurs at entry level, most probably due to the lack of HIV-1 receptors. In contrast, human testis explants can support infection by an HIV-1 X4R5 strain. The nature of the infected cells within this tissue is currently under investigation.
365 INVESTIGATING THE LATE STAGES OF THE HIV-1 LIFE CYCLE IN A LOW-LEVEL, LONG-LIVED, MICROGLIA INFECTION MODEL
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 365)
R Vos, A Albright and F González-Scarano
Productively infected microglia displayed an expected abundance of intracellular p55, with an average p24/p55 ratio of 0.35. In contrast, quiescently infected microglia had an aberrant processing pattern in which there was an abundance of intracellular p24 in relation to p55: densitometric analysis showed an average p24/p55 ratio of 4. Treatment of the quiescently infected cells with a protease inhibitor did not lead to viral particle release, indicating that premature processing is not responsible for the replication block seen in our model. Initial electron microscopy studies indicate a reduction in the number of budding particles on the surface of microglia cultured without serum/cytokines. Current studies focus on localization of the structural proteins and analysis of microarray data to gain clues pertaining to the cellular environment required for full support of the HIV life cycle in microglia.
Session 52PO - Poster
Immunopathogenesis, Immunotherapy and Vaccines
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 52.01PO - Poster
HIV-Induced Immune Dysfunction and Activation
366 CD38 EXPRESSION, VIRAL GENOTYPE AND HIV PATHOGENESIS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 366)
JD Klausner1, R Donovan2, M Gesner2, K Steiner1 and HW Sheppard2
Decreased immune activation was associated with PIresistant viral genotype and could explain some clinical observations of decreased disease progression in patients infected with PI-resistant virus. Immune activation continues to play an important role in disease pathogenesis necessitating that future studies of disease progression should include measures of immune activation, including CD8 CD38 expression.
367 THE EFFECT OF HIV-1 NEF EXPRESSION ON DENDRITIC CELLS AND MACROPHAGES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 367)
Y Yokota1, M Isogai1 and K Otake2
Although cells of the monocyte lineage, such as macrophages (Mfs) and dendritic cells (DCs), are targets for HIV infection, little is known about the effect of Nef on these cells compared to that on T cells.
368 THE HEAT SHOCK PROTEIN RECEPTOR CD91 IS UP-REGULATED IN MONOCYTES OF HIV-1-INFECTED ‘TRUE’ LONG-TERM NON-PROGRESSORS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 368)
J Stebbing1, S Portsmouth1, A Wildfire1, F Gotch1, M Nelson1, M Bower1, S Shaunak1, P Srivastava2, B Gazzard1, S Patterson1
A small proportion of human immunodeficiency virus type 1 (HIV-1)-infected individuals remain asymptomatic for a long period post-infection. It is thought that a vigorous immune response may contribute to long-term non-progression, although studies are confounded by heterogeneity among patients.
369 HIV-1 PATIENTS WHO START HAART WITH LOW CD4 T-CELL COUNTS AND RETAIN PLASMA VIRAL RNA HAVE HIGHER CYTOKINE mRNA LEVELS IN STIMULATED PBMC AND HIGHER SERUM SOLUBLE CD30 THAN EQUIVALENT PATIENTS WHO CLEAR THEIR VIRUS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 369)
S Lee, P Price and M French
This study assessed long-term immunological changes in immune reconstituted patients with different virological outcome during highly active antiretroviral therapy (HAART). The study group comprised seven ‘complete responders’ with good immunological responses (increases of >100 CD4 T cells/µl) and virological responses (plasma HIV RNA levels <400 copies/ml) and six ‘discordant responders’ with increased CD4 T-cell counts despite a persistent viraemia.
370 ACTIVATION OF THE BLOOD–BRAIN BARRIER REQUIRES A CELLULAR AS WELL AS A VIRAL COMPONENT
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 370)
AG MacLean, D Bieniemy, X Alvarez, T Rasmussen and AA Lackner
We have shown that the primary cell infected during acute SIV neuropathogenesis is the monocyte-derived macrophage. It is assumed that these cells bring virus into the brain. We have demonstrated there is activation of the blood–brain barrier (BBB) during acute SIV infection and at terminal AIDS. However, it has never been determined if there is a requirement for the virus to be carried through the BBB or if the BBB can be activated with cell free virus.
371 IMMUNE ACTIVATION AND MEMORY T CELLS INCREASE IS OBSERVED IN VIETNAMESE HIV-1 EXPOSED BUT UNINFECTED DRUG USERS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 371)
TK Hung1, TX Lien1, LT Tram1, NV Ngai2, CT Cuc1, F Barré-Sinoussi3, G Pancino3 and D Scott-Algara3
Lymphocyte phenotypes are indicative of a general augmentation of memory cell populations and especially of an expansion of activated CD8+ cells in EU IDU compared to controls. These data are consistent with a putative role of CD8+ cell subset in the natural resistance against HIV-1 infection in Vietnamese EU IDU.
372 T-CELL RECEPTOR-STIMULATED NAÏVE CD4+ T-CELLS FROM HIV-INFECTED INDIVIDUALS HAVE IMPAIRED Ki67 EXPRESSION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 372)
SF Sieg, DA Bazdar and MM Lederman
TCR-activated naïve CD4+ T cells from HIV-infected subjects display qualitative defects in Ki67 expression. The failure of IL-2 to restore Ki67 expression in naïve CD4+ T cells from some patients could be related to events downstream of STAT-5 phosphorylation or to events unrelated to IL- 2 receptor signalling. These results suggest that IL-2 may have limited adjuvant activity for naïve CD4+ T cells in a subpopulation of HIVinfected individuals.
373 EVIDENCE THAT CHRONIC IMMUNE ACTIVATION IN HEALTHY NON HIV-1-INFECTED ETHIOPIANS OCCURS AT EARLY AGE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 373)
A Tsegaye1, N Vrisekoop2, S Otto2, D Wolday1, B Petros3, S Tilahun1, A Admassu1, A Lakew1, T Assefa4, E Sanders1, M Hazenberg2, D Van Baarle2 and F Miedema2
Chronic immune activation plays a major role in HIV-1 infection, which is characterised by low (naïve) CD4+ T cell numbers, increased T cell division and a decreased T cell receptor excision circle (TREC) content. To further elucidate this role, we studied chronic immune activation independent of HIV.
374 CD4+CD25+ T CELLS IN SIV INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 374)
I Pandrea, C Apetrei, PA Marx, AA Lackner and RS Veazey
CD4+ T cells constitutively expressing IL-2 receptor alpha chain (CD25) may be important in suppressing immune responses being involved in regulating transplantation tolerance, preventing autoimmune responses, and inhibiting both mitogen and anti-CD3-induced proliferative responses. These cells, termed T regulatory cells (Treg) are characterized based upon functional, rather than phenotypic characteristics and definitive markers for Treg cells are currently lacking. In humans, CD4+CD25+ regulatory cells express CTLA-4 and CD45RO but not CD69. Little data exist on the dynamics of this population in HIV or SIV infections.
375 CHRONIC IMMUNE ACTIVATION OF HIV INFECTION RESULTS IN IMPAIRED SIGNAL TRANSDUCTION AND ANERGY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 375)
Q Leng, G Borkow and Z Bentwich
Elevated expression of Cbl-b and CTLA-4 accompany and are probably causal for impaired phosphorylation of ERK-1/2 and cellular response during HIV-1 infection. 2) These changes are the result of chronic immune activation and lead to impaired immune response and anergy. 3) The anergy-inducing elements of chronic immune activation may also impair immune reconstitution during HAART, and should therefore serve as potential targets for therapy during HIV infection.
376 SEVERE EARLY IMMUNODEPRESSION IN AFRICAN HIV-1-INFECTED CHILDREN AS COMPARED TO UNINFECTED CHILDREN
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 376)
I Viho1, F Rouet1,2, A Inwoley1,2, D Ekouevi2,L Bequet2, C Rouzioux3, V Leroy2,4 and F Dabis2,4, for the ANRS 1201/1202 Ditrame Plus Study Group
Independently of clinical data that are usually hard to interpret in the first months of life, the paediatric CD4+ percentage appeared as a useful and informative marker for the early identification and treatment decision of African immunodepressed HIV-1-infected neonates.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 52.02PO - Poster
Cellular Suppressive Factors
377 A SOLUBLE FACTOR SECRETED FROM LPS-STIMULATED MACROPHAGES INHIBITS THE REPLICATION OF X4 HIV-1 ISOLATES IN BOTH MACROPHAGES AND T LYMPHOCYTES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 377)
A Verani1, J Mikulak1, AG Siccardi2 and P Lusso1
We have shown that bacterial lipopolysaccharide (LPS) protected primary human monocyte-derived macrophages (MDM) from productive infection by CCR5 tropic HIV-1 isolates largely through the release of RANTES, MIP-1α and MIP-1β. The finding that CXCR4 was a functional co-receptor for HIV-1 infection of macrophages prompted us to investigate the effects of bacterial LPS on MDM infected with CXCR4 (X4) HIV-1 isolates.
378 HIV-2 SPECIFIC β-CHEMOKINE PRODUCTION AND ANTIVIRAL ACTIVITY IN HIV-2-INFECTED INDIVIDUALS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 378)
RKS Ahmed1, B Makitalo1, K Karlen1, S Andersson1, A Blaxhult2, G Biberfeld1 and R Thorstensson1
These preliminary results suggest that CD8+ T cell-mediated antiviral activity is more frequently present in HIV-2- infected patients compared to HIV-1-infected LTNP.
379 MECHANISM OF CD8+ SUPPRESSION OF HIV IN OLDER CHILDREN
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 379)
B Katz, B Salimi and B Patterson
These preliminary observations suggest that genes with known effects on HIV, such as LIF, MBP or Hck, may be responsible for some CAF activity in children. We could not confirm the importance alpha-defensins in children with CD8-suppression. Prospective studies of CD8-suppression in children need to be performed to further elucidate the nature and mechanism of action of CAF.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 52.03PO - Poster
Innate Immunity
380 HAART INDUCE THE TOLEROGENIC MOLECULE HLA-G ON PERIPHERAL MONOCYTES FROM HIV-1-INFECTED PATIENTS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 380)
J Peña1, A Cabello1, A Rivero2, MJ Garcia1, JM Lozano1, R González1, G Dueñas1, E Vidal2, MD Galiani1, M Santamaria1, R Solana1, A Camacho2 and JM Kindelán2
We have observed that most of HIV-1-seropostive individuals, who are not receiving HAART express low levels of HLA-G in PBMCs. Based on this, here we analyse the possibility that the expression of HLA-G could be induce by HAART.
381 ROLE OF FRESHLY ISOLATED AND ACTIVATED NATURAL KILLER CELLS IN HUMAN HIV-1 INFECTION: EFFECT OF HIV-1 VIRAEMIA ON EXPRESSION AND FUNCTION OF INHIBITORY AND ACTIVATING RECEPTORS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 381)
D Mavilio1, M Daucher1, J Benjamin1, A Malaspina1, S Kottilil1, G Lombardo1, AM Planta1, E Marcenaro1, A Moretta2, L Moretta2,3 and AS Fauci1
HIV-1 plasma viraemia dysregulates inhibitory NK receptors (up-regulated) and NCR (down-regulated), and that this correlates with impaired NK cell cytotoxic function. This phenomenon is not due to a direct HIV-1 infection of NK cells. Thus, this study may provide insight into the mechanisms of impaired host defences in HIV-viraemic patients.
382 EFFECTOR CD4 T-CELL MYELOPEROXIDASE EXPRESSION: EVIDENCE OF INNATE-TYPE IMMUNE MOLECULES IN T-CELL POOLS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 382)
RL Hengel1,2, V Thaker1, RA Lempicki3 and HC Lane1
MPO gene and protein expression was found in CD4 T cells. A greater than 10-fold increased expression of MPO mRNA was found among CD62L– effector comparted to CD62L+ memory CD4 T cells. These data point to additional connections between innate and adaptive immunity and suggest that, in addition to regulatory functions, CD4+ T cells many have direct effector functions.
383 HIV-1 INHIBITS NK CELL FUNCTION IN VITRO
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 383)
L Valor-Mendez, K Weber, T Horvath, RE Schmidt and H Heiken
HIV-1 reduces NK cell activity in vitro by PBMC but not by isolated NK cells. This inhibition can be blocked by using a chemokine or a chemokine receptor antagonist. This reduced NK cytotoxicity was not due to cell death or defective cell proliferation. Cell to cell interaction and the release of soluble factors upon HIV-1 co-incubation could be a possible explanation for the observed effect.
384 ACTIVATION THROUGH FcγR INHIBITS HIV-1 INTEGRATION IN MACROPHAGES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 384)
A David, D Perez-Bercoff, M Wlodarczyk, P Versmisse, F Barré-Sinoussi and G Pancino
Activation of primary macrophages through FcγR cross-linking results in the inhibition of HIV-1 integration in host cell genome. This suggests that the stimulation of macrophages by immune complexes may affect HIV-1 replication in vivo. In addition, this is a unique model for studying cell factors interfering with HIV-1 replication in primary cells.
385 CD8+ T CELLS CONTROL REPLICATION OF NONPATHOGENIC SHIV89.6 IN SOME, BUT NOT ALL RHESUS MACAQUES – A ROLE FOR INNATE RESPONSES?
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 385)
K Abel1,2, E Chung4, L Fritts2, S Amrute4, T Rourke2, P Fitzgerald-Bocarsly4 and CJ Miller1–3
In three of four SHIV89.6-infected monkeys with undetectable plasma vRNA CD8 T cell depletion resulted in a rapid increase of plasma vRNA comparable to acute infection peak vRNA levels. Concurrent with viral rebound, PBMC IFN-γ mRNA levels and SIV-specific IFN-γ responses were reduced. Reappearance of CD8 T cells was paralleled by increasing IFN-γ responses and rapidly diminishing vRNA levels. In one of four monkeys only 200 viral copies could be detected after CD8 depletion. Thus, CD8 cells were not responsible for control of SHIV89.6 replication. The analysis of interferon alpha (IFN-α) responses after CD8 depletion showed that in this monkey the number of plasmacytoid dendritic cells (PDC) and IFN-α production were increased in response to in vitro virus challenge. In contrast, monkeys with viral rebound had reduced numbers of PDC. Thus, control of SHIV89.6 replication was associated with CD8+ T cells and IFN-γ production in three of four monkeys, but with increased IFN-α+ responses in one of four monkeys. Therefore, in different individuals different host immune mechanisms can contribute to control of SHIV89.6 replication.
386 IN VITRO SUSCEPTIBILITY TO HIV-1 INFECTION OF PERIPHERAL BLOOD MONONUCLEAR CELLS OF SERONEGATIVE PARTNERS OF HIV-1-INFECTED INDIVIDUALS IN CAMBODIA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 386)
M Nguyen1, J Nouhin1, N Ly1, R Ing1, V Phoung1, F Barré-Sinoussi2, JM Reynes1 and G Pancinco2
An in vitro system to study the susceptibility to HIV-1 infection according to cell activation status was established. According to our results, in vitro resistance to HIV-1 is not associated with the apparent protection in Cambodian EU partners of HIV+ infected individuals. Infectivity assays on isolated CD4+ cells alone or in the presence of CD8+ cells are in progress in order to evaluate the role of these cell subsets in PBMC resistance to HIV-1 infection.
387 HEAT-SHOCK PROTEIN 70 IS AN INNATE IMMUNITY FACTOR THAT ANTAGONIZES HIV-1 VIRAL PROTEIN R
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 387)
M Bukrinsky1, S Iordanskiy1and Y Zhao2
Heat-shock protein 70 (Hsp70) is a member of a family of molecular chaperones that contribute to innate immunity and protection from environmental stress. Binding of HSPs to HIV-1 proteins can enhance antiviral immunity, including natural killer (NK), antibody-dependent (ADCC), gamma delta T-cell and cytotoxic T-lymphocyte (CTL) activities against HIV-1-infected cells. Heat-shock proteins Hsp27 and Hsp70 are selectively expressed early after HIV-1 infection, suggesting that expression of these proteins might be a part of the host innate antiviral immune responses. However, the specific targets of heat shock proteins and their role in responses to HIV infection are still unclear.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 52.04PO - Poster
HIV-Specific Humoral Immunity
388 INVOLVEMENT OF FCγ RECEPTORS IN THE MECHANISM OF PRIMARY HIV-1 INHIBITION BY POLYCLONAL IgG PURIFIED FROM INFECTED PATIENTS IN CULTURED MONOCYTES-DERIVED MACROPHAGES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 388)
V Holl1, S Hemmetter1, R Burrer1, N Lagarde1, S Schmidt1, S Haessig1, A Bohbot2, AM Aubertin1 and C Moog1
The aim of this study was to investigate the mechanism of HIV-1 neutralization using monocytes-derived macrophages (MDM) instead of PBMC as target cells. For this purpose, we analysed neutralizing activities of different human polyclonal IgG purified from sera of HIV-1 infected individuals using a single-cycle infection assay.
389 NEUTRALIZING POLYCLONAL IMMUNOGLOBULIN G FROM HIV INFECTED PATIENTS BIND FREE HIV PRIMARY ISOLATES WITHOUT INTERFERING WITH THE INITIAL CD4-DEPENDENT ATTACHMENT OF VIRUS TO PBMC
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 389)
C Moog1, R Burrer2, S Haessig-Einius1 and AM Aubertin1
We investigated the relationship between HIV-1 primary isolates (PIs) antibody-mediated neutralization and attachment to PBMC. Incubation of PIs with IgG purified from infected patients did not inhibit attachment of the viruses with PBMC, while partial to complete neutralization was achieved. Neutralization of PIs already fixed on the cells was achieved by some IgG samples only, and was of limited intensity compared to the former neutralization protocol.
390 TAT-NEUTRALIZING HUMAN MONOCLONAL ANTIBODIES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 390)
E Moreau and C Desgranges
HIV regulatory protein Tat is essential for viral replication as a transcription factor. Tat is also released extracellularly in its active form by infected cells and can exhert various functions as a viral toxin. Thus, Tat may be an excellent target for vaccination or passive imunization with human monoclonal antibodies (HMAbs). The purpose of this study was to produce HMAbs and to define their functional properties against Tat.
391 EVALUATION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 SUBTYPE C NEUTRALIZATION BY FLOW CYTOMETRIC QUANTITATION OF INTRACELLULAR P24 ANTIGEN IN SINGLE ROUND INFECTION OF PRIMARY CELLS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 391)
E Gray, N Taylor and L Morris
An important goal of an effective human immunodeficiency virus type 1 (HIV-1) vaccine is to induce a broadly protective neutralizing antibody response. Accurate quantification of antibody-mediated neutralization of primary HIV-1 isolates is required for studies of the mechanism of virus neutralization and for assessment of immune responses to candidate vaccines. Subtype C is one of the most prevalent genetic subtypes of HIV-1 in the world and the most common in southern Africa. In preparation for HIV-1 vaccine clinical trials we evaluated a method of measuring HIV-1 neutralization by flow cytometric detection of intracellular p24 with the inclusion of a protease inhibitor (indinavir) to quantify first-round infected cells.
392 AUTOLOGOUS NEUTRALIZATION AND NEUTRALIZATION ESCAPE IN HIV-2 INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 392)
Y Shi1,2, E Brandin1, A Blaxhult3, K Gyllensten3, C Broström3, EM Fenyö2 and J Albert1
Neutralization escape, which is very common in HIV-1 infection, appears to be more rare in HIV-2 infection. If this is a cause or a consequence of the lower virulence of HIV-2 remains to be established.
393 CHARACTERISTICS OF SERUM IgA IN HIV-2-EXPOSED UNINFECTED INDIVIDUALS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 393)
L Qin1,2, C Nilsson1,2, S Andersson3, M Ehnlund2, S Sourial1 and E Björling1,2
The mechanisms behind the resistance of human immunodeficiency virus type 2 (HIV-2) infection are still not fully understood. In the present study, we explore the HIV-2-specific humoral serum immunoglobulin A (sIgA) immune response in HIV-2-exposed uninfected (EU) individuals. Serum samples from heterosexual EU females and their known HIV-2-infected partners, and controls originating from Guinea-Bissau in Africa were studied. Antibody reactivity to native and recombinant envelope glycoproteins was investigated.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 52.05PO - Poster
HIV-Specific Cellular Immunity
394 HYDROXYUREA MAY INCREASE THE LEVEL OF ANTI-HIV SPECIFIC CD8+ T CELLS (CTLs) IN CHRONIC HIV INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 394)
M López, J Benito, S Lozano, P Martinez, J González-Lahoz and V Soriano
HU may increase CTL responses, even in patients with undetectable VL, this supporting the role of HU as an immunomodulatory agent.
395 HIV-SPECIFIC CYTOTOXIC T LYMPHOCYTE CLONE UNABLE TO KILL HIV-INFECTED CELLS SHOWS INCREASED BINDING CAPACITY TO PEPTIDE-HLA COMPLEX
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 395)
T Ueno, H Tomiyama, M Fujiwara and M Takiguchi
To investigate why CD8 T cell response fails ultimately to control HIV infection despite the presence of HIV-specific CD8 T cells in vivo, we sought to re-evaluate HIV-specific cytotoxic T lymphocyte (CTL) clones generated so far by focusing on another aspect. Here, we examined two CTL clones, designated 55 and 589 having Vδ1.1/Vβ13.3 and Vα12.1/Vβ5.6 TCR, respectively.
396 CROSS-PRESENTATION OF HIV-1 EPITOPES FROM LIVE AS WELL AS APOPTOTIC INFECTED CD4+ T CELLS IS MORE EFFICIENT THAN DIRECT VIRAL PRESENTATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 396)
C Marañón, JF Dessouter, G Hoeffel, W Cohen and A Hosmalin
Unexpectedly, HIV antigen internalization and cross-presentation by DC from live infected cells was as efficient as from apototic infected cells. These comparative data attempt to assess the most relevant HIV presentation mechanism in infected patients. Since cross-presentation of minute amounts of viral proteins from live or apoptotic HIV-infected T cells is possible, this presentation pathway should be exploited to purge latent viral reservoirs and obtain better viral replication control. Supported by ANRS, Ensemble contre le SIDA and INSERM Category 3.5: HIV-specific cellular immunity.
397 ASSOCIATION PATTERNS BETWEEN PLASMA VIRAL LOAD, PROVIRAL LOAD, AND T-CELL IMMUNE RESPONSES IN HIV-1 INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 397)
V Novitsky1, P Gilbert2, T Peter3, T Ndung’u3, N Rybak1, MF McLane1, TH Lee1 and M Essex1
A significant inverse correlation between VL and TCIR in HIV-1C infection was shown for Gag p24, while direct correlation was observed for high Nef-specific TCIR. There was significant association between total TCIR and PR, as well as between Pol-based TCIR and PR.
398 IDENTIFICATION OF CONTROLLERS, NORMAL PROGRESSORS, AND PROGRESSORS BY IMMUNOPHENOTYPING, AND RNA QUANTIFICATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 398)
S Gappoo1, P Chetty1, U Govender1, JD Harlow1, C Henry1, I Honeyborne1, N Mngqundaniso1, N Nene1, N Ntumba1, D Ramduth1, P Kiepiela1, P Goulder2 and HM Coovadia1
There is a significant decline in CD4% and CD4 absolute values (<12%; <200 cells/mm3, respectively), when the viral is >100,000 RNA copies/ml. Perhaps this effect could be more profound if the sample size was increased and there was a longer follow up period. The confounding variable is the unknown time of HIV infection in all three groups.
399 PROMINENCE OF HLA-C-RESTRICTED CTL ACTIVITY IN THE HIV-SPECIFIC RESPONSE IN CLADE C INFECTED AFRICAN ZULU/XHOSA IN DURBAN
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 399)
I Honeyborne1, D Ramduth1, P Chetty1, N Nene1, N Mngquandaniso1, N Ntuba1, U Govender1, C Henry1, S Gappoo1, H Coovadia1, M Altfeld3, M Addo3, P Kiepiela1 and P Goulder2
The C locus of the HLAI may play an important role regarding which epitopes are efficiently presented to CTLs during immune response to HIV-1. The HLA C locus type of a patient may be important in the effectiveness of controlling the virus.
400 IDENTIFICATION OF HIV-1-SPECIFIC CD4+ RESTRICTED EPITOPES IN C-CLADE INFECTED AFRICAN ZULU/XHOSA IN DURBAN
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 400)
D Ramduth1, P Kiepiela1, M Addo3, M Altfeld3, P Chetty1, H Coovadia1, S Gappoo1, U Govender1, J Harlow1-3, C Henry1, I Honeyborne1, N Mngqandaniso1, N Nene1, N Ntumba1 and PJ Goulder2
This study aimed to assess the frequency of Th cell responses in Clade-C infected patients using overlapping peptide pools encompassing the entire HIV genome, and individual peptides to map CD4 restricted epitopes. An ELISPOT screen was carried out on 397 Clade-C infected patients to determine which peptides induced a strong inteferon-gamma (IFN-γ) response.
401 DEGRADATION OF HIV-1 ANTIGENS BY DIFFERENT PROTEASES AND GENERATION OF CD8 T-CELL EPITOPES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 401)
J Choppin, J Caumartin, W Cohen, H Gahéry and JG Guillet
Proteasomes isolated from EBV-transformed B cells or lymphoma T1 cells cleaved synthetic substrates very efficiently after Tyr and Arg, but not after Lys. Other cytosolic proteases extracted from EBV-B cells cleaved efficiently substrates after Tyr and Lys, and also cleaved Nef 66-100 after Lys82. Our preliminary results suggested that they may be homologues of calpains. Such proteases are possibly responsible for the liberation of certain epitopes having a Lys at COOH-terminal end and being potentially presented by molecules of the HLA-A3 supertype.
402 INDUCIBLE NITRIC OXIDE SYNTHASE EXPRESSED BY CERVICAL MACROPHAGES IN HIV WOMEN CO-INFECTED BY HUMAN PAPILLOMA VIRUS (HPV)
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 402)
ATG Fernandes1, A Nicol1, F Silva1, B Grinstejn1, F Russomano1, O Martinez-Maza2 and MG Bonecini-Almeida1
HPV infection undergoes a period of clinical latency, but reappears frequently in HIV seropositive women, whose have great susceptibility to develop cervical cancer disease. Local immunity response play a critical role in controling these infections. Furthermore, HIV and HPV can modulate macrophage apoptotic pathways through several mediators, including cytokines and nitric oxide. The aim of this study was to analyse the frequency and distribution of macrophage and iNOS in cervical HPV infection.
403 DIFFERENCES IN GAG-SPECIFIC CELLULAR IMMUNE RESPONSES ARE ASSOCIATED WITH HIV-1 DISEASE PROGRESSION IN A CLADE A OR D INFECTED UGANDAN COHORT
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 403)
J Serwanga1, S Rowland2-1, C Watera1, P Kaleebu1, R Ingram1,2, J Whitworth1 and F Gotch2
We hypothesize that IFN-γ responses seen in RPs may represent T-cell responses with dysfunctional cytolytic properties resulting into disease progression. Furthermore, we show that clade-specificity of the responses is not necessarily associated with HIV-1 disease progression.
404 INTER-LABORATORY EVALUATION OF HIV SPECIFIC IFN-GAMMA ELISPOT ASSAY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 404)
C Durier1, A Samri2, A Urrutia3, H Gahery-Segard4, S Imbart5, I Sanchez1, E Tartour5, A Venet3, JP Aboulker1, B Autran2 and the ANRS ELISpot Standardization group
These data show good inter-laboratory concordance with only the set of peptides and ELISpot reader in common but suggest that the adoption of further reference standard operative procedure should improve the standardization of IFN-γ ELISpot assay.
405 THE CYTOSOLIC ENZYME TPPII, AND NOT THE PROTEASOME, PROCESSES THE HIV-1 IMMUNODOMINANT Nef73–82 EPITOPE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 405)
A Hosmalin1, U Seifert2, C Marañón1, JF Desoutter1, S Dietscher3, L Wesoloski2, K Janek2, H de la Salle4, M Andrieu1, D Laderach5, A Galy5, G Haas3 and P Kloetzel2
CD8+ T cell responses are required for HIV control. They are induced after stimulation of the T cells by MHC class I molecule–epitope complexes. Most MHC class I-restricted epitopes are generated in the cytosol by enzymatic cleavage by the proteasome. However, some epitopes are proteasome-independent. We have studied an immunodominant HIV-1 epitope restricted by HLA-A3/A11/B35, Nef73-82.
406 PRESENCE OF HIV-SPECIFIC CD4+ T-CELL PROLIFERATIVE RESPONSES IN HIV-INFECTED SUBJECTS WITH SUSTAINED VIROLOGICAL CONTROL FOLLOWING HAART
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 406)
C Lacabaratz-Porret1, J-P Viard2, C Goujard3, Y Levy4, C Deveau5, A Venet1 and M Sinet1
The influence of both the duration of virus control and the degree of immunodeficiency (CD4+ T cells <200/ml) before HAART on HIVspecific CD4+ T-cell proliferative responses may explain apparent discrepancies between different previous studies. These results suggest that HIV-specific proliferative response may be observed in chronically infected subjects treated even at a significant degree of CD4+ T-cell depletion provided the time of virus suppression is long enough, which may have implications for future therapeutic strategies.
407 SURVEY OF HIV-SPECIFIC IMMUNE RESPONSES IN HLA-A2-EXPRESSING, HAART-NAÏVE, HIV POSITIVE SUBJECTS IN THE CHRONIC PHASE OF INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 407)
Y Peretz, G Alter, CM Tsoukas and NF Bernard
We found no evidence in this study population that the intensity or breadth of the HIV response correlated with either reduced viral load (i.e., controlled viraemia) or increased viral load (i.e., was driven by the level of viraemia).
408 IN VITRO STIMULATION WITH RECOMBINANT MODIFIED VACCINIA VIRUS ANKARA GENERATES HIV-1-SPECIFIC T-CELL RESPONSES IN HIV-1 EXPOSED INFANTS DURING THE FIRST YEAR OF LIFE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 408)
JA Slyker1,3,5, T Hanke2, BL Lohman1,6, GC John-Stewart3,6, DA Mbori-Ngacha4,EGT Wee2, AJ McMichael2 and SL Rowland-Jones5
These data suggest responses to unidentified epitopes in the gag region of HIVA may contribute to the high immunogenicity observed in the exposed uninfected infants. We conclude that MVA.HIVA is highly immunogenic in vitro, and may be useful in evaluating immune responses in HIV-1- exposed individuals and vaccinees.
409 IN VIVO CONTAINMENT OF SIV REPLICATION ASSOCIATED WITH INDUCTION OF BROAD MULTISPECIFIC CYTOTOXIC T LYMPHOCYTES DIRECTED AGAINST CONSERVED VIRAL EPITOPES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 409)
P Villefroy1, F Letourneur1, L Mortara1, Z Coutsinos1, H Gras-Masse2, C Beyer3, AM Aubertin3, A Venet1, JG Guillet1 and I Bourgault-Villada1
We investigated the role of multispecific cytotoxic T lymphocyte (CTL) responses induced by a lipopeptide simian immunodeficiency virus (SIV) vaccine in protecting rhesus macaques from a highly pathogenic SIVmac251 challenge.
410 FUNCTIONAL IMPAIRMENT OF EBV AND HIV-SPECIFIC CD8+ T CELLS IN HIV-INFECTION: CD27 PROVIDES A CLUE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 410)
D Van Baarle, C Jansen, C Bronke, E Piriou, K Tesselaar and F Miedema
Despite detectable virus-specific CD8+ T cells in most HIV-infected patients, immune surveillance is eventually lost, leading to progression to AIDS. In addition, loss of control over Epstein-Barr virus (EBV) may cause AIDS-related non-Hodgkin’s lymphomas (AIDSNHL).
411 CONTROL OF HUMAN T HELPER CELL DIFFERENTIATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no.411 )
L Rogge, S Gasparian and F Letimier
Effective HIV-specific helper T cell responses are of critical importance for immunological control of the virus. In order to understand the genetic program that controls the differentiation and functional properties of T helper 1 (Th1) versus T helper 2 (Th2) cells, we have compared the gene expression profiles of human Th1 and Th2 cells using high-density oligonucleotide arrays with the capacity to display transcript levels of 6000 human genes.
412 VIRAL INFECTION PERSISTENCE BUT NOT LEVEL OF VIRAEMIA LEADS TO ABLATION OF HIV-SPECIFIC CD4 AND CD8 T-CELLS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 412)
B Yassine Diab1, AE Kernaleguen1, S Younes1, R Boulassal2, C Tremblay2, D Rouleau2, JP Routy2 and RP Sekaly1
Several studies provide strong evidence that CD4+ Th cells play a critical role in determining the persistence of memory and effector CTLs in viral infections. HIV-specific CD4+ and CD8+ T cells are maintained in LTNP and in individuals treated with HAART suggesting the presence of a strong memory T cell compartment. However, chronically infected individuals show a profound suppression of HIV-specific proliferation and cytokine production despite the maintenance of effector HIV-specific T cells. These observations suggest that the phase of primary infection (PI) is a determinant step in the maintenance of HIV specific memory T cell responses.
413 PRESSURE FROM CYTOTOXIC T CELLS AND PROTEASE INHIBITORS ON THE HIV-1 PROTEASE GENE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 413)
AC Karlsson1, SG Deeks2, JD Barbour1, BD Heiken1, SR Younger1, R Hoh2, M Lane2, M Sällberg3, GM Ortiz1, JF Demarest4, T Liegler1, RM Grant1-2, JN Martin2 and DF Nixon1
Antigen-specific cytotoxic T lymphocytes (CTL) can exert significant selection pressures on HIV-1 that can lead to the development of viral escape mutants, resulting in loss of immune control. In addition, antiretroviral drugs also select for drug escape mutations. Given the complex nature of viral evolution under drug-pressure we reasoned that HIV-specific cellular immune responses directed at epitopes within protease could influence viral evolution during antiretroviral therapy. 29 HIV-infected subjects failing a protease inhibitors (PI) containing regimen were sampled.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 52.06PO - Poster
HIV-Specific Mucosal Immunity
414 T-HELPER CELL RESPONSES TO HIV-1 IN THE CERVIX OF HIGHLY EXPOSED, PERSISTENTLY SERONEGATIVE FEMALE SEX WORKERS IN NAIROBI, KENYA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 414)
P Thottingal1,3, R Kaul2, KR Fowke1, J Kimani3, C Wachihi3, W Jaoko3 and FA Plummer1
ICCS will likely be a valuable tool in the detection and quantification of CD4+ cellular responses at the genital tract level, although assay methods are still undergoing refinement. CD4+ cervical responses are weak or absent in the genital tract of HIV-infected subjects, but can be detected in a subgroup of sexually exposed HEPS women. Preliminary results suggest that virus-specific CD4+ responses may be compartmentalized in the genital tract of these women.
415 STUDY OF LANGERHANS CELLS INFECTION BY HIV-1 IN AN IN VITRO RECONSTITUTED VAGINAL MUCOSA MODEL
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 415)
P Sivard1, C Dezutter-Dambuyant2, J Kanitakis3, H Hamzeh1, F Cognasse1, JF Mosnier4, L Misery1 and C Genin1
We performed an in vitro reconstituted mucosa integrating Langerhans cells (LC) and we investigated the LC infection by HIV-1 in this model. The epithelium consisted of vaginal keratinocytes from hysterectomy tissue fragments cultured on de-epidermized dermis in submerged medium for 2 weeks.
416 SELECTIVE SEQUESTRATION OF X4 HIV ISOLATES BY THE ENDOCERVICAL CELL LINE HEC1A: INVOLVEMENT IN HIV TROPISM SELECTION PROCESS DURING HETEROSEXUAL TRANSMISSION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 416)
W Berlier1, T Bourlet1, H Hamzeh1, C Lambert2, B Verrier3, C Genin1,2, B Pozzetto1 and O Delézay1
In order to evaluate the potential contribution of the epithelial cells of the human female genital tract in the R5 tropism selection process during heterosexual transmission of HIV, we analysed the interaction between HIV and the HEC1A human endocervical cell line. Galactosylceramide (an alternative HIV receptor) and CXCR4 were detected by flow cytometry on 14% and 59% of viable cells, respectively. Neither CD4 nor CCR5 were evidenced on cells surface.
417 MODELISATION OF A VAGINAL MUCOSA INTEGRATING LANGERHANS CELLS WITH A HUMAN EXOCERVICAL CELL LINE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 417)
M Cremel1, H Hamzeh1, C Lambert1, JC Berningo2, C Meric3, O Delezay1 and C Genin1
A reconstructed vaginal mucosal model was developed by using a human epithelial cell line from the exocervix (SiHa cells). Flow cytometry analysis demonstrated that these cells had similar phenotypical characteristics than normal vaginal cells. The two main HIV coreceptors CXCR4 and CCR5 were evidenced on the cell surfaces as well as the alternative HIV receptor, galactosylceramide.
418 OPTIMIZATION OF METHODS TO ASSESS HUMAN MUCOSAL T-CELL RESPONSES TO HIV INFECTION AND VACCINATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 418)
BL Shacklett1, O Yang2, MA Hausner3, J Elliott4, L Hultin3, C Price3, M Fuerst4, J Matud3, P Hultin3, C Cox1, J Ibarrondo3, JT Wong5, DF Nixon1, PA Anton4 and BD Jamieson3
The majority of HIV-1 infections occur via sexual transmission at mucosal epithelia lining the vagina, cervix or rectum. Mucosal tissues also serve as viral reservoirs. However, our knowledge of human mucosal T-cell responses is limited. There is a need for reliable, sensitive and reproducible methods for assessing mucosal immunity. Here we report on the collaborative efforts of two laboratories to optimize methods for processing, culturing and analysing mucosal lymphocytes.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 52.07PO - Poster
T-Cell Homeostasis
419 HOMEOSTATIC REGULATION OF NAÏVE AND MEMORY T CELLS: IMPLICATIONS FOR VIRAL AND CELLULAR DYNAMICS IN HIV INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 419)
Z Grossman1,2, B Min1 and WE Paul1
During HIV infection, memory to recall antigens is lost early-on, uninfected T cells show functional abnormalities, and &naiuml;ve CD4 T cells are preferentially depleted despite their relative resistance to infection. These observations are poorly understood. Advances in lymphocyte dynamics suggest that they reflect pathophysiologic responses to regulatory controls.
420 CD4+ T-CELL DYNAMIC IN SIV-INFECTED MACAQUES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 420)
R Ho Tsong Fang, V Monceaux, MC Cumont, B Hurtrel and J Estaquier
The dynamic basis for CD4 T-cell depletion in AIDS remains controversial. To adress this major issue, we explore T-cell death and T-cell dynamic in peripheral blood as well as in lymph nodes of macaques infected with a pathogenic SIVmac251 strain or with a non pathogenic SIVmac251Δnef clone. We used Ki67 expression to assess cycling T cells in the blood and lymph nodes. During the asymptomatic phase of infection, the number of cycling CD8+ T cells progressively increase (two- to eightfold) both in the blood and in the lymph nodes of macaques infected with the SIVmac251 strain.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 52.08PO - Poster
Determinants of Protection
421 SOLUBLE CCR5: A NOVEL CANDIDATE FOR NATURAL PROTECTION AGAINST HIV INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 421)
A Tsimanis1, A Kalinkovich2 and Z Bentwich3
1) sCCR5 and MIP-1β serum levels are probably interdependent and constitute two lines of defence against HIV infection. 2) The amounts of sCCR5 found in plasma is much higher than the reported amount of membrane bound CCR5. 3) The role of sCCR5 in the pathogenesis of HIV infection and its natural course should be further explored.
422 THE RELATIONSHIP BETWEEN IFN-γ RESPONSES IN LYMPHOID TISSUES OF SHIV89.6-IMMUNIZED RHESUS MACAQUES AND CHALLENGE OUTCOME AFTER INTRAVAGINAL CHALLENGE WITH SIVMAC239
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 422)
K Abel1,2, TA Reinhart4, L La Franco-Scheuch1,2, T Rourke2, V de Silva2, BA Fallert4 and CJ Miller1-3
When viral RNA levels were plotted against IFN-γ mRNA and protein levels in lymphoid tissues, a normal distribution pattern was observed. Protected monkeys, consistent with low virus replication, had the lowest IFN-γ mRNA levels, but were able to secrete IFN-γ in response to SIV antigen in vitro. Thus, CTL effector functions were maintained. Intermediate to high virus replication in vaccinatedunprotected monkeys was associated with increased IFN-γ mRNA levels and strong SIV-specific IFN-γ ELISPOT responses. Vaccinenaïve animals had the highest levels of virus replication, but an impaired ability to secrete IFN-γ. Further, vaccinated-unprotected and vaccine-naïve monkeys had increased levels of Mig and IP-10 chemokines that attracted CXCR3-positive activated T cells to lymphoid tissues. Therefore, persistent IFN-γ responses contributed to chronic inflammation and disease progression. Further, IFN-γ responses in lymphoid tissues were not accurately reflected in PBMC IFN-γ responses. Thus, the idea that strong IFN-γ responses are associated with protection should be interpreted with caution.
423 EFFECT OF SEX HORMONES ON SUSCEPTIBILITY TO HIV-1 INFECTION IN WOMEN
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 423)
C Kaushic, T Graham, A Gillgrass and KL Rosenthal
In heterosexual transmission of HIV-1 from male to female the virus has to enter and infect cells of the female reproductive tract. The cells in the female reproductive tract that are potential targets for HIV remain poorly defined. HIV infection is two step process requiring a primary receptor and a co-receptor. We have started to examine the expression of HIV receptors in the female genital tract and localize the cells that express these receptors.
424 BOTH SYSTEMIC AND LOCAL HIV-SPECIFIC IMMUNE RESPONSES CAN BE DETECTED IN MULTIEXPOSED NON INFECTED INDIVIDUALS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 424)
A Suy, M Plana, F Garcia, O Coll, A Garcia, MJ Maleno, C Gil, M Arnedo, LL Alos, JJ Barcelo, T Pumarola, T Gallart and JM Gatell
HIVspecific cellular immune responses could be detected in a quarter of sexually exposed uninfected individuals. Other factors such as genetic advantages, humoral immunity or soluble factors should be involved in the protection of the rest of the serodiscordants couples.
425 HUMAN α DEFENSIN CONTRIBUTION TO THE HIV-EXPOSED BUT UNINFECTED STATUS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 425)
D Trabattoni1, S Lo Caputo2, G Maffeis1, M Saresella3, F Vichi2, M Biasin1, P Pierotti2, M Franchini4, P Ferrante3, F Mazzotta2 and M Clerici1
Human a defensin 1, 2 and 3 may play an important anti-HIV-1 role in long-term non-progressors. The contribution of these molecules to the HIV-exposed but uninfected status was analysed in PBMC, cervical-vaginal mononuclear cells (CVMC) and cervical biopsies of nine HIV-1-exposed uninfected women (ESN), 10 HIV-infected patients (HIV) and 13 low-risk healthy controls (HC).
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 52.09PO - Poster
Immune Reconstitution
426 IMMUNE RECONSTITUTION IN HIV-INFECTED PATIENTS WITH SUSTAINED UNDETECTABLE PLASMA VIRAL LOAD
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 426)
I Poizot-Martin1, M-P Drogoul-Vey1, C Marimoutou1, C Tamalet2, F Dignat-George3, P Colson2, C Brunnet3, R Grégoire4, V Pradel4 and JA Gastaut1
Immune restoration is effective in patients with sustained plasma RNA undetectability, moreover when associated to RNAcell undetectability. The lower restoration observed in pretreated patients should be linked to their lower CD4+ cell count at initiation of the considered therapy.
427 FREQUENCY OF IMMUNE RECONSTITUTION SYNDROME AMONG HIV–TB CO-INFECTED INDIVIDUALS AFTER INITIATION OF GENERIC ANTIRETROVIRAL THERAPY IN INDIA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 427)
N Kumarasamy1, SK Chaguturu2, T Yepthomi1, TP Flanigan2, P Balakrishnan1, S Solomon1, CCJ Carpenter2 and KH Mayer2
With increased access to antiretroviral therapy and incidence of opportunistic infections in the developing world, clinicians must understand the epidemiology and clinical characteristics of IRS and ameliorate symptoms without compromising clinical care. There is an urgent need to develop guidelines for initiation of antiretroviral therapy in the context of opportunistic infections in the developing world.
428 IMMUNE RESTORATION DISEASE (IRD) DURING FIRST 6 MONTHS OF HAART
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 428)
A Wnuk, M Pynka, D Bander and A Boron-Kaczmarska
1) Starting HAART before profound immunodeficiency results in relatively low incidence of IRD. 2) In short-term observation the response to antiretroviral treatment in HCV co-infected patients is comparable with those HIV-positive only.
429 VIRUS BURDEN, IMMUNOARCHITECTURAL CHANGES IN LYMPHOID TISSUES IN HIV-1-INFECTED PATIENTS (PTS) TREATED 18 MONTHS WITH HAART WITH OR WITHOUT PI:PROF3002 ATTILA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 429)
P Racz1, C Tenner-Racz1, D Praindhui2, A Goetschel2, G Carcelain3, N Delphin4, V Schneider4 and W Rozenbaum5
To evaluate the effect of HAART with triple NUC (±PI) on HIV-1 RNA level in plasma (pVL) and lymphoid tissues (vRNA). In this pilot study, pts with a pVL >5000 copies/ml received Trizivir™ (TZV) or a quadruple therapy (QUAD) with Combivir™ + abacavir + Agenerase™ for 72 weeks (wks). Adverse events (AE), pVL, CD4+ cell count were assessed every 2 months. Immune reconstitution in blood and lymph nodes (LN) and guts biopsies fixed for in situ hybridization and immunohistochemical analysis were performed at baseline (BL), wk 24 and 72.
430 HIV+ INDIVIDUALS HAVE HIGH PERCENTAGES OF CTLA-4+CD4+ REGULATORY T CELLS DESPITE SUCCESSFUL LONG-TERM HAART
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 430)
SF Stone, P Price and MA French
Evidence is mounting that restored immune responses against both HIV and non-HIV antigens may be short-lived or decrease progressively during long-term highly active antiretroviral therapy (HAART), often without a drop in CD4+ T-cell counts. The time on HAART required to restore pathogen-specific immune responses and the magnitude of the restored response also vary considerably between individual patients, even when CD4+ T-cell counts are similar. To determine if immunosuppressive factors may be responsible, we have investigated the potential role of CD4+ regulatory T cells expressing cytotoxic T-lymphocyte antigen-4 (CTLA-4) in individuals successfully treated with HAART.
431 PARTIAL VIRAEMIA CONTROL IS ASSOCIATED WITH FAVOURABLE OUTCOME IN HIV INFECTED PATIENTS IN ANTIRETROVIRAL COMBINATION THERAPY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 431)
R Rodrigues1,2, M Sanchez3, J Casseb2, AJS Duarte2, CR Gonzales2 and LFM Brígido3
Markers such as CD4+ T cells count and ESR prior to initiation of treatment may predict a positive CD4 gain. Partially sustained control of viraemia, even with detectable VL, may lead to positive outcomes. Studies to address this issue will improve clinical management and provide clues in HIV pathogenesis.
432 EVALUATION OF IMMUNOLOGIC RESTORATION IN HIV-INFECTED INDIVIDUALS TREATED WITH HAART BY MEASURING THE IMMUNE RESPONSE UPON RABIES VACCINATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 432)
FP Kroon1, SMC Snabel2, CM Jol Van Der Zijde2, DMC Brinkman2, MJD Van Tol2 and JT Van Dissel1
The majority of HIV-infected individuals treated with HAART are able to mount a humoral immune response after primary vaccination and an enhanced response after booster vaccination with a T cell-dependent neoantigen like rabies vaccine. However, the immune response is quantitatively still impaired in comparison with healthy controls. Since a primary and secondary immune response demands a properly functioning immune system, we conclude that 8 months, or more, of HAART – irrespective of the CD4+ T-cell counts – leads to a partially restored immune response to T cell-dependent neoantigens.
433 LONG-TERM CD4+ T-CELLS RESPONSE TO HIGHLY ACTIVE ANTIRETROVIRAL THERAPY ACCORDING TO BASELINE CD4+ T-CELL COUNT AND AGE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 433)
G Felipe, E de Lazzari, M Plana, G Mestre, E Martínez, J Mallolas, JL Blanco, JM Miró, T Pumarola, T Gallart and JM Gatell
The increase of CD4+ T cells in antiretroviral-naïve patients treated with HAART reached a plateau after 3 years of HAART, and the rate and magnitude of increase was not influenced by baseline CD4+ T cells or age. Those patients with a baseline CD4+ T-cell count below 350 cells/mm3 had poorer immunological outcome.
434 INTERLEUKIN-7 LEVELS PREDICT TREATMENT RESPONSE IN ADVANCED HIV-INFECTED SUBJECTS RECEIVING LOPINAVIR/RITONAVIR-BASED THERAPY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 434)
JP Routy, GHR Smith, N Gilmore, M Klein, T Murphy, J MacLeod, R LeBlanc, J Allan, P René, RG Lalonde and MR Boulassel
Interleukin-7 (IL-7) is a cytokine known to regulate lymphocyte development and homeostasis. Recent data indicate that IL-7 levels may be associated with disease progression in HIV-infected subjects. Here we examined prognostic value of pre-treatment IL-7 levels on immune and viral parameters in advanced HIV-infected patients receiving lopinavir/ritonavir-based therapy.
435 THE PROGNOSTIC SIGNIFICANCE OF BASAL CD4 CELL COUNTS ON IMMUNOLOGIC AND VIROLOGIC RESPONSES TO ANTIRETROVIRAL THERAPY (ART) IN AIDS PATIENTS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 435)
D Jevtovic, R Jovan, D Salemovic and S Zerjav
Complete suppression of viral replication and immunologic reconstitution was less likely to be achieved in patients with basal CD4 below 100, especially if HAART regimens without PIs were used. However, in patients with pretreatment CD4 counts above 100 it was possible to escape from the risk zone for developing opportunistic infections with triple therapy not containing PIs.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 52.10PO - Poster
Primary Infection
436 DIMINISHED TRANSMISSION OF M184V RESISTANT VARIANTS AND PROTEASE (PR) POLYMORPHISMS IN PRIMARY HIV-1 INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 436)
MA Wainberg1–3, D Turner1, BG Brenner1, D Moisi1, Z Rosberger1, B Spira1 and JP Routy3
The lower incidence of M184V in PHI may reflect its impact in lowering viral fitness and viraemia. Conversely, the decreased prevalence of PR polymorphisms may be related to a delaying in recent years in treatment commencement and higher viraemia in some transmitters.
437 EX VIVO LYMPHOCYTE PROLIFERATION AND ACTIVATION DURING PRIMARY INFECTION IN MACAQUES INFECTED WITH SIVmac251 AND TREATED WITH HAART
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 437)
B Vaslin1, K Benlhassan-Chahour1, C Penit2, V Dioszeghy1, F Vasseur2, G Janvier4, Y Rivière4, N Dereuddre-Bosquet3, D Dormont1 and R Le Grand1
Lymphocyte proliferation during primary SIV infection seems to be associated with viral replication. High plasma concentration of antiviral is associated with a better control of viral load during treatment and weak lymphocyte proliferation. However percentage of circulating CD8+CD28+/CD28– cells expressing IFN-γ appears to be increased in both groups of HAART-treated animals.
438 LEVELS OF PLASMA HIV RNA AND CD4 T CELLS AFTER DISCONTINUATION OF HAART INITIATED WITHIN SIX MONTHS OF SEROCONVERSION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 438)
C Zala, A Krolewiecki, A Federico, A Gun, C Ochoa, B Bouzas and P Cahn
Following >24 weeks of treatment interruption, plasma HIV RNA levels reached a plateau below pre-therapy levels in SC but not in CR patients. However, the effect of HAART in SC seems to be limited to prevent a drop of CD4 T cells after treatment discontinuation.
439 EARLY DETECTION OF HIV INFECTION USING FOURTH-GENERATION ASSAY AS A SCREENING TEST IN A HIGH PREVALENCE POPULATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 439)
I Zapiola, L Mammana, S Fernandez Giuliano and MB Bouzas
The inclusion of a 4th gen assay in the diagnostic algorithm allowed us the identification of four patients ongoing seroconversion via p24 Ag detection. For clinical laboratories, is important to address the p24 Ag sensitivity of the 4th gen assays when they are selected. High sensitivities for HIV antibodies and for p24 Ag are needed in order to detect early seroconversion samples specially in high HIV prevalence groups to provide an opportunity for early initiation of treatment, counselling and to reduce the risk of transmission.
440 CLINICAL AND LABORATORY MANIFESTATIONS OF ACUTE HIV INFECTION IN ZAMBIA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 440)
U Fideli1-3, the Rwanda/Zambia HIV Research Group2-4
Seroconversion was associated with an increase in relatively mild nonspecific signs and symptoms. ‘Flu syndrome’ was not reported, but suspected malaria may be analogous. Men and women differed in their clinical presentation and ESR levels. Symptomatic seroconverters developed higher viral load setpoints. A simple scoring system can identify individuals at higher risk for seroconversion, however, studies of symptomatic seroconverters will not be generalizable to the majority of people who do not have an ‘acute infection syndrome’.
441 HAS HIV INFECTION BY ITSELF ANY EFFECT ON MITOCHONDRIAL (MT) DNA CONTENT?
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 441)
S López1, Ò Miró1, E Martínez2, E Pedrol3, A Beato1, E Deig3, JM Gatell2, J Casademont1 and F Cardellach1
We demonstrate that mt DNA depletion can be promoted by the proper HIV infection or concomitant conditions. Further investigations are necessary to elucidate the mechanism/s implicated, although several hypotheses around the HIV infectionderived apoptotic processes induced by the mitochondrial pathway have been invoked. Supported by FIPSE 3102/00 and Fundació la Marató de TV3 02/0210.
442 DIVERSITY OF VIROLOGICAL MARKERS DURING ACUTE AND EARLY HIV-1 INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 442)
ML Chaix1, C Deveau2, I Pellegrin3, C Goujard4, N Matignon1, N Ngo1, M Harzic5, I Garrigue3, C Tamalet6, L Meyer2, C Rouzioux1, the ANRS PRIMO Cohort Study Group
We report a large diversity in virological markers levels at the time of primary infection with a wide range of HIV RNA including very low values even in patients enrolled rapidly after infection or presenting with clinical symptoms. Moreover, this study demonstrates a very early establishment of the proviral DNA level.
443 WEAK EXPOSURE OF THE 2G12 NEUTRALIZING EPITOPE ON ENVELOPES FROM PRIMARY ISOLATES COLLECTED DURING PRIMARY INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 443)
L Dacheux1, Y Ataman2, F Biron1, B Verrier2 and F Barin1
A few human monoclonal antibodies to the HIV-1 envelope glycoproteins are able to neutralize a broad range of primary isolates. The aim of our study is to analyse the kinetics of exposure of the corresponding neutralizing epitopes during the infection course. To this respect, we studied the antigenicity of the envelope glycoproteins of primary isolate quasispecies present during primary infection and several years later in two patients.
444 NON-PATHOGENIC INFECTION OF MANDRILLS BY SIVmnd TYPE 1 OR SIVmnd TYPE 2 IS ASSOCIATED WITH HIGH VIRAL LOAD AND GENETIC DIVERSITY BUT NOT WITH T-CELL ACTIVATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 444)
R Onanga1, S Souquière1, M Makuwa1, F Simon2 and P Roques1
Mandrills are infected by SIVmnd-1 and SIVmnd-2. SIVmnd-2 clusters with SIVmnd-1 in env, and with SIVrcm in gag-pol. SIVmnd-2 harbours a vpx gene, while SIVmnd-1 does not. SIVmnd-1 and SIVmnd-2 infections are apparently non-pathogenic in mandrills. Many studies showed that early virus–host interactions predict the level of viral control and disease progression in HIV-1-infected humans, thus we investigated the dynamics and the variability of SIVmnd, as well as cell activation levels during the primary infection in mandrills.
445 THE ROLE OF HIV-1 PROVIRAL DNA IN THE DIAGNOSIS OF PRIMARY HIV INFECTION IN CLINICAL PRACTICE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 445)
NA Medland1, T Middleton2, C Birch2 and D Smith3
Although DNA amplification can shorten the window period for the diagnosis of primary HIV infection (PHI) little evaluation of this assay has been performed in the clinical setting. Patients presenting to an urban primary care clinic with signs and symptoms consistent with PHI, or a recent exposure to HIV were evaluated with HIV EIA, Western Blot (WB), and HIV Proviral DNA, by Roche Amplicor (DNA). Quantitative HIV RNA testing, by Roche Monitor RT-PCR, was performed on specimens positive for any test. 14 (8.6%) of 163 DNA tests over 4 years were positive.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 52.11PO - Poster
MHC and Host Genetic Factors
446 MHC CLASS II HLA-DR ALLELE FREQUENCIES IN BOTSWANA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 446)
T Ndung’u1, S Gaseitsiwe1, F Doualla-Bell1, T Peter1, E Sepako1, I Thior1, V Novitsky2 and M Essex2
This is the first study to identify the most common HLA class II alleles on a population level in Botswana. Preliminary analysis shows that the frequencies and distribution of different HLA-DRB allele groups among Batswana may differ from that reported from North American and European populations. Vaccine studies that target elicitation of CD4 T-helper responses may therefore have to take account of these differences, assuming that T-helper responses are desirable in efficacious HIV-1 vaccines. Future studies may help elucidate the role that HLA-DRB polymorphisms may play in disease pathogenesis.
447 HLA CLASS I ASSOCIATION WITH HIV VIRAL LOAD/CD4 IN A COHORT IN DURBAN, SOUTH AFRICA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 447)
CA Henry1, P Kiepiela1, P Chetty1, S Gappoo1, N Mngundaniso1, N Nene1, N Ntumba1, D Ramduth1, HM Coovadia1 and P Goulder2
Similar CD4% and CD4 absolute count was noted for patients regardless of the class I molecule within controllers and progressors. This could be due to the small number of patients in each group. There were no progressors with B57, B81 and A66 class I molecule. These class I molecules, particular B57 is a known controller of HIV infection and could be the explanation that there were no progressors. No significant differences in viral load estimation was found within controllers and progressors regardless of the HLA class I molecule.
448 IMMUNOLOGICAL DIFFERENCES IN PATIENTS EXPRESSING SUBTYPES OF HLA-B58 IN A LOCAL BLACK POPULATION IN DURBAN, SOUTH AFRICA
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 448)
P Chetty1, S Gapoo1, J Harlow3, C Henry1, I Honeyborne1, P Kiepiela1, A Leslie2, N Mngqundaniso1, N Nene1, N Ntumba1, D Ramduth1, H Coovadia1 and P Goulder2
Significant differences in the magnitude and breadth of responses elicited by HLA-B57 and B5801 as compared to HLA-B5802 is clearly shown using the methods described above. This study demonstrates that HLA subtyping is important when considering clinical outcomes and disease progression in infected individuals.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 52.12PO - Poster
Host Regulatory Genes
449 SOLUBLE gp120 INDUCES THE ACTIVATION AND PRODUCTION OF CELLULAR FACTORS CONTRIBUTING TO THE HIV REPLICATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 449)
F Veas, D Misse, A Mechulam, J Gajardo, H Yssel and M Cerutti
Secreted proteins from HIV are able to induce different and complex intracellular signalling pathways. Some of these are MAP-Kinases or PIK3 exhibiting differences in function of the nature of the target cells Most of these activations induce cellular functions as pro-inflammatory cytokines, chemokines production chemotactism, apoptosis or production of different cytotoxic factors and proteases. In our study we observed differential gene and protein expression induced in primary cord cells and peripheral blood mononuclear cells in the presence or in the absence of soluble gp120.
450 TOWARD THE DEFINITION OF THE HIV-1-HOST CELL INTERACTOME AS A TOOL TO IDENTIFY NEW THERAPEUTIC TARGETS AGAINST HIV-1 INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 450)
JC Rain1, S Emiliani2, M Maroun2, F Martin1, E Segeral2, N Heveker2, L Selig1, P Legrain1 and R Benarous2
Most anti-HIV drugs currently used are targeted against catalytic activities of viral enzymes. However, a better understanding of the dynamic interplay between host cell and virus might be crucial to control HIV infection. We designed a project aiming to: i) elucidate the multiple interactions that HIV contracts with the host cell during the virus life cycle; ii) define new cellular targets that are essential for HIV replication; iii) design and screen for novel compounds able to disrupt these key interactions as a basis for future anti-HIV therapeutics.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 52.13PO - Poster
Long-term Non-Progressors
452 INFECTION WITH HUMAN HERPES VIRUSES 6, 7 AND 8 IN LONG-TERM NON-PROGRESSORS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 452)
H Agut1, D Boutolleau1, A Gautheret-Dejean1, V Calvez1 and D Costagliola2, for the French ANRS ALT Study Group
Progression was observed for 53 LTNP (75%). The detection of HHV-7 DNAemia was more frequent than that of HHV-6 : 48 vs 6%, 53 vs 5%, and 47 vs 7% at the 3 yearly evaluations, respectively. HHV-7 DNA load was consistently low (median <200 EqCop/106 PBMC) and did not correlate either positively or negatively with CD4 cell count, HIV-1 load and progression. Twenty LTNP (28%) were HHV-8-seropositive and did not exhibit any significant difference regarding CD4 cell count, HIV-1 viral load and proportion of subjects remaining LTNP over time when compared to their HHV-8-seronegative counterparts. HHV-8 DNAemia was infrequently detected (10% of samples tested) and median viral load was low (468 EqCop/106 PBMC). In conclusion, HHV-6 reactivation was infrequent whereas HHV-7 reactivation and HHV-8 infection were frequent in LTNP. None of these three viruses appeared to be a co-factor of HIV progression.
453 LONG-TERM FOLLOW-UP OF HIV-INFECTED WOMEN IN KIGALI, RWANDA: THE IMPACT OF HIV DISEASE AND GENOCIDE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 453)
J Meinzen-Derr1 and the Rwanda/Zambia HIV Research Group2–4
Of 401 HIV+ women followed for 16 years since their first HIV+ serology, half have died during peace time, most due to AIDS-related illnesses. Approximately a fifth of the women have died as a result of war and a tenth of the women have been lost to follow-up. The remaining 20% are alive and in relatively good health.
454 NONPROGRESSORS IN THE AUSTRALIAN LONG-TERM NONPROGRESSOR COHORT: PROPORTIONS AND PREDICTORS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 454)
J Guerin1, L Ashton2, J Amin1, K McGhie3,4, P Cunningham3,4, G Stewart5, J Sullivan6, N Deacon7, A Kelleher1,4, D Cooper1 and J Kaldor1, on behalf of the LTNP Study Group
Within this highly selective cohort 30 individuals retained their LTNP status despite being infected for 15 years, however, the proportion of true non-progressors with HIV-1 infection remains to be established. Further studies are required to identify additional determinants of true non-progressors in individuals without known factors predictive of LTNP.
455 LONG-TERM NONPROGRESSIVE HIV INFECTIONS IN B57+ PATIENTS ARE NOT ASSOCIATED WITH KIR3DL1 AND MIC ALLELES AND NKG2D EXPRESSION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 455)
WL Shupert1, SA Migueles1, P Martin2, M Carrington2 and M Connors1
In conclusion, the differential ability of B57+ LTNP and patients with progressive disease to restrict HIV replication does not appear to be associated with the presence of specific KIR3DL1 and MIC alleles or NKG2D expression levels.
456 HIGH FREQUENCY OF GROSS DELETED nef GENE IN LONG-TERM SURVIVORS TREATED WITH KOREAN RED GINSENG FOR 11 YEARS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 456)
YK Cho, HK Lee, HS Yang, SH Ahn and HJ Lee
The size of deletion was different in all and larger than 94 bp except all 15 bp deletion in seven clones in a patient with subtype D. In the eight out of 17 individuals, at least two deleted nef genes were obtained. The number of the individuals with gross deleted nef gene was 11 (65%). The possibility of cross-contamination was seriously checked. In conclusion, our 11 years’ data show that there is an association between slow progression by the longterm intake of KRG and nef gene variation including deletion in vivo.
457 A DESCRIPTIVE STUDY OF PAEDIATRIC HUMAN IMMUNODEFICIENCY VIRUS-INFECTED LONG-TERM SURVIVORS, IN THE CARIBBEAN NATION OF BARBADOS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 457)
A Kumar and MA St John
Significantly higher proportion of females as compared to males survived beyond their eighth birthday. Over four-fifths of the long-term survivors remained asymptomatic or developed only mild sign or symptoms on follow-up.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 52.14PO - Poster
Mechanisms of CD4 T-cell Depletion
458 ANTIGEN-DRIVEN SKEWED MATURATION OF HIV-1 SPECIFIC CD4+ T CELLS IN VIRAEMIC PATIENTS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 458)
SA Younes1, BY Diab1, T Cameron3, LH Kalfayan1, AE Kernaleguen1, R Boulassel1, JP Routy1, L Stern2 and RP Sekaly1
CD4+ T cells are the major target of HIV-1 infection in humans. Little is known regarding the frequency and the breadth of HIV-1 epitope specific CD4+ T cells in HIV-1-infected patients. We studied the CD4+ T cell response in 33 long term HAART-treated aviraemic and in eight viraemic patients having a history of therapy interruption. Using p24, p17 and Nef overlapping peptides, the CFSE dye, and the intracellular staining techniques we found that Gag and Nef specific CD4+ cells are detectable after an average of 25 months of therapy initiation. The breadth of the response was monitored using MHC class II DR1-tetramers and a CFSE-based proliferation assay.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 52.15PO - Poster
Dendritic Cells in HIV Pathogenesis
459 PERIPHERAL BLOOD DENDRITIC CELLS IN HIV-INFECTED PATIENTS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 459)
BK Møller
In conclusion, phenotypical changes in DC of HIV patients are modest, but activation as deducted from increased expression of HLA-DR is not reflected in modulations of CD86 or CXCR4 expression.
460 DEFICIENT TYPE I INTERFERON PRODUCTION AND CIRCULATING DENDRITIC CELL NUMBERS AS EARLY AS THE PRIMARY STAGE OF HIV-1 INFECTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 460)
S Kahi1, M Lichtner1, L Develioglu1, O Amar1, C Deveau2, L Meyer2, C Goujard3, M Sinet4, P Lebon5 and A Hosmalin1
Successful immunological control of HIV infection is only achieved in rare individuals. DCs are required for specific antigen presentation to naïve T lymphocytes and for antiviral, type I IFN secretion. We had previously found a decreased blood myeloid DC proportion in chronic HIV+ patients. We studied patients during the primary stage, which is critical for setting a balance between the host immune response and the virus. HIV patients were studied 16 to 159 days (n=25) after the presumed date of infection.
461 HIV INDUCES DENDRITIC CELL CYTOTOXICITY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 461)
M Lichtner1,6, C Marañón1, PO Vidalain2, O Azocar2, D Hanau3, P Lebon4, M Burgard5, C Rouzioux5, V Vullo6, H Yagita7, C Rabourdin-Combe2, C Servet2 and A Hosmalin1
Induction of cytotoxicity in DCs by HIV might contribute to HIV-associated T cell depletion through induction of apoptosis, especially in the early stages of infection. It may also participate in eliminating infected cells in vivo, thereby enhancing cross-presentation of HIV by DCs. Therefore, this new cytotoxic function of DCs may play an important role in innate and adaptive immunity during HIV infection.
462 SUBSTANCE P INCREASES EXPRESSION AND FUNCTIONALITY OF CCR5 CO-RECEPTOR ON DENDRITIC CELLS/LANGERHANS CELLS AND THEIR PRECURSORS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 462)
H Hamzeh1, O Sabido2, L Misery3, O Delézay1 and C Genin1
Substance P (SP) is a neuropeptide that increases in vitro HIV-1 replication in macrophages. Dendritic cells/Langerhans cells (DC/LC) are the main targets of HIV in mucosae but allow only weak viral replication. We studied the effects of SP on CXCR4 and CCR5 HIV coreceptors expression on these cells. Cord blood CD34+ progenitors were cultured for 12 days with GM-CSF, TNFα and TGF-β1 in order to obtain DC/LC expressing Langerin, a specific marker of the Langerhans cell lineage.
463 WHEN INTEGRATED IN A CHORION EQUIVALENT, DENDRITIC CELLS KEEP THEIR IMMATURE STAGE AND THEIR ABILITY TO REPLICATE TYPE R5 HIV-1 STRAINS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 463)
J Valladeau, S Dumont, N Bechetoille, S Maréchal, S Gofflo, D Schmitt and C Dezutter-Dambuyant
In primary HIV-1 infection, dendritic cells (DC) are used by the virus to traverse the epithelial barrier of the female genital tract. in vitro, the replication of monocyte (M)-tropic strains is hypothesized to be efficient in immature DC but not in cultured mature DC although infectious virus can be efficiently transmitted to CD4+ T cells. We focused our interest on the susceptibility of human interstitial DC (IntDC) to be infected after M- and T lymphocyte (T)-tropic strains exposure when they were integrated in a reconstructed lamina propria.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 52.16PO - Poster
HIV-Induced Apoptosis
465 CASPASE-DEPENDENT AND -INDEPENDENT T-CELL DEATH PATHWAYS IN PATHOGENIC SIMIAN IMMUNODEFICIENCY VIRUS INFECTION: RELATIONSHIP WITH DISEASE EVOLUTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 465)
J Estaquier1,2, D Arnoult1, F Petit1, JD Lelièvre1, V Monceaux2, R Ho Tsong Fang2, B Hurtrel2 and JC Ameisen1
Studies performed in human immunodeficiency virus (HIV) and nonhuman primate models of pathogenic and non-pathogenic simian immunodeficiency virus (HIV) infections have suggested that enhanced ex vivo CD4 T cell death is a feature of in vivo pathogenic infection. However, no studies have addressed the relative contribution of the extrinsic and intrinsic pathways to programmed T-cell death in SIV infection. Here, we report that the ex vivo extent of spontaneous death of CD4+ T cells from pathogenic SIVmac251-infected rhesus macaques is correlated with the in vivo extent of CD4 T-cell depletion and plasma viral load.
466 APOPTOTIC PROPERTIES OF THE HIV-1 REGULATORY PROTEIN Vpr: STUDY OF THE INTERACTION BETWEEN Vpr AND THE ADENINE NUCLEOTIDE TRANSLOCATOR, IN VITRO AND IN VIVO NEUROTOXICITY OF Vpr
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 466)
E Sabbah1, S Druillennec1, N Morellet1, S Bouaziz1, G Kroemer2, F Noble1 and BP Roques1
Viral protein R, Vpr, one HIV-1 accessory protein, is a 96 amino acids protein, highly conserved among the lentiviruses. The discovery of circulating Vpr in the cerebrospinal fluid and serum of seropositiv patients and the apoptotic properties of Vpr over different cellular types in vitro prompt us to hypothesize that Vpr may be responsible, at least in part, for the depletion of cells and the neurodegenerescence phenomenons associated to AIDS. Thus, we looked for the cellular partner(s) of Vpr during the apoptotic process, and discovered that Vpr interacts with the adenine nucleotide translocator (ANT) (coll. G. Kroemer).
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 52.17PO - Poster
Cytokines in HIV Pathogenesis
467 REGULATION OF THE SDF-1 PROMOTER BY TRANSACTIVATING VIRAL PROTEINS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 467)
JM Alonso-Lobo1, C García-Moruja2, M Bermejo1, N González1, F Arenzana-Seisdedos3, A Caruz2 and J Alcamí1
Basal expression of the SDF-1 promoter is dependent on regulatory sequences located between the -590/-501 region from the transcription start site. Induction of the SDF-1 promoter was observed by different stimuli and in particular by co-expression of regulatory viral proteins.
468 DEFECTIVE IL-2-DEPENDENT JAK/STAT SIGNALLING IN THE CD4 AND CD8 T LYMPHOCYTES FROM HIV+ PATIENTS: REVERSAL BY HAART
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 468)
M Kryworuchko1, V Pasquier1, H Keller1, D David1, C Goujard2, J Gilquin3, JP Viard4, M Joussemet5, JF Delfraissy2 and J Thèze1
HIV infection leads to a profound T cell dysfunction well before the clinical onset of AIDS. We have been accumulating evidence that one of the mechanisms responsible for this T cell deficiency may be the dysregulation of signal transduction via the interleukin (IL)2/IL-2 receptor (R) complex. In CD4 T lymphocytes from untreated HIV+ patients, IL-2 is unable to induce entry into the cell cycle. HAART corrected only partially this dysfunction.
469 MECHANISM FOR HIV TAT REGULATION OF CYTOKINE EXPRESSION: KINASE SIGNALLING AND PKR-MEDIATED IMMUNE RESPONSE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 469)
JCB Li, DCW Lee and AS Lau
Our results indicate that PKR activity is required in mediating the transcriptional effects of NF-κB in Tat-induced cytokine expression including IL-10. Induction of IL-10 may result in suppression of T cell activities in vivo. In conclusion, PKR plays a critical role in mediating the effects of HIV Tat on the immune system. (Supported by grants to AS Lau from Hong Kong Research Grants Council and Ho Tung Paediatrics Research Fund.)
470 INHIBITION OF HIV-1 REPLICATION IN PRIMARY CELLS BY A PAF-RECEPTOR ANTAGONIST
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 470)
L Moreira, RG Lima, PT Bozza, HC Castro-Faria-Neto and DC Bou-Habib
We observed that 10 µM of BN 52021 strongly inhibited HIV-1 replication in these cells (mean ±SEM=72 ±12%; n=3), and, as observed for PBMCs, concentrations of BN 52021 up to 50 µM did not result in increased inhibition. Apparently, BN 52021 is more efficient in suppressing HIV-1 growth in macrophages than in PBMCs. Our results warrant further investigation on the role of PAF as an up-regulator of viral replication in primary HIV-1 target cells.
471 CYTOKINE POLYMORPHISM GENE AND INTRALESIONAL LEVELS OF CYTOKINES IN HUMAN PAPILLOMAVIRUS (HPV)-INFECTION, HIV-INFECTION AND SQUAMOUS INTRAEPITHELIAL LESIONS (SIL)
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 471)
APM Fernandes, MAG Gonçalves, RT Simoes, AA Faccio and EA Donadi
We identified host genetic polymorphism that may be associated with HPV 16 infection and SIL risk, some of which have been linked to potential functional effects on immune responses. Our results suggest that in LG-SIL the increased IL-10 intralesional secretion may be associated with the down-regulation of anti-tumour immunity. On the other hand, HG-SIL seems to be associated with increased levels of TNF- α.
472 EFFECT OF HIV INFECTION ON CYTOKINES IN LYMPHOID TISSUE INFECTED EX VIVO
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 472)
A Audigé1, E Schlaepfer1, A Bonanomi2, D Nadal2 and RF Speck1
Although there are considerable differences in the cytokine profile, HIV replication was supported by both tonsillar blocks and HLAC. The observed lack of a cytokine response in both culture systems may represent an HIV-specific mechanism to suppress the generation of an effective cellular immune response.
473 HIV-1 PATHOGENESIS AND VIRAL IN INFECTED HUMAN LYMPHOID TISSUE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 473)
JC Grivel, Y Ito, W Fitzgerald, S Chen, Y Kiselyeva and L Margolis
Upon infection HIV-1 diverges into a ‘swarm’ of viral quasispecies, whose dominant forms change in the course of the disease. In particular, CCR5-utilizing (R5) HIV-1 variants generally dominate early HIV-1 infection, whereas later CXC4-using variants (R5/X4 or X4) evolve and this evolution is associated with an acceleration of disease progression. Neither the cause of the viral evolution, nor the mechanism( s) of its association with disease progression are fully understood.
474 CYTOKINES OF THE PLACENTAL ENVIRONMENT INVOLVED IN THE CONTROL OF HIV-1 MOTHER-TO-CHILD TRANSMISSION: HISTOCULTURES AS A NEW MODEL OF STUDY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 474)
G Dolcini1, A Faye1-2, S Pornprasert1, J Taïeb3, JL Taupin4, P Ave1, M Derrien1, G Chaouat2, F Barré-Sinoussi1 and E Menu1-2
Altogether, these data indicate that placental histocultures is a suitable and reliable new ex vivo model to study the placental environment and its modification upon various stimuli such as HIV and antiretroviral drugs.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 52.18PO - Poster
Biological Markers for Monitoring Disease Progression and Therapy
475 AFFORDABLE HIV-1 MONITORING: A DIRECT COMPARISON OF AN IMPROVED P24 ANTIGEN ASSAY AND THE ROCHE AMPLICOR MONITOR ASSAY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 475)
G Stevens, N Rekviashvili, L Scott and W Stevens
South Africa has one of the fastest growing human immunodeficiency virus (HIV) epidemics and the largest number of people living with HIV/AIDS in the world. HIV/AIDS is the most important challenge to the economic development of Southern Africa. Measuring HIV-1 RNA load in plasma has now become a critical marker for predicting and monitoring disease progression for people on HAART.
476 A COST EFFECTIVE ALTERNATIVE VIRAL LOAD ASSAY FOR AFRICA: CORRELATION OF CAVIDI EXAVIR LOAD QUANTITATIVE HIV-RT KIT WITH ROCHE AMPLICOR MONITOR VERSION 1.5
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 476)
N Rekhviashvili, G Stevens, G Corrigan, L Scott and W Stevens
The Actuarial Society of South Africa estimated the number of people infected with HIV in the country at 5.3 million as at the middle of 2000. This data highlights the importance of finding more cost effective and simple alternative assays for detection and monitoring of HIV-1 viral load. The existing gold standards are still simply unaffordable for Africa. Our study evaluates the use of a new, improved ExaVir Load kit (Cavidi) for HIV-1 quantitation in a resource poor setting.
477 CORRELATION OF CD4 T CELLS WITH TOTAL LYMPHOCYTE COUNTS (TLC) – A MARKER FOR MONITORING HIV/AIDS PATIENTS IN RESOURCE LIMITED SETTINGS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 477)
BJ Srihari1, M Jacob1, S Rajasekaran2, CV Bhirmanandham1 and NM Samuel1
This preliminary study reveals that good correlation exists between CD4 T cells and TLC counts in both normals and HIV symptomatic patients. As it is an ongoing study, clear picture will emerge when large numbers are studied. However, it is evident from this study that TLC can be used in place of CD4 T cell counts in resource-limited settings to monitor the HIV disease state and particularly valuable while monitoring ART, thus to save the money to the poor.
478 CLINICAL PROGNOSIS OF ENFUVIRTIDE IN COMBINATION WITH AN OPTIMIZED BACKGROUND REGIMEN AMONG CATEGORIES OF BASELINE CD4+ CELL COUNT AND HIV ANTIRETROVIRAL RESISTANCE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 478)
J Hornberger1,2 and J Green3
The clinical prognosis was more favorable with ENF + OB than with OB alone across all five subgroups. ENF is expected to provide greater benefit in prognosis among patients in the higher BL CD4 subgroup and those with remaining active antiretroviral therapy options (higher GSS).
479 RELATIVE QUANTIFICATION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 PROVIRAL DNA IN CD4+ LYMPHOCYTES BY LIGHTCYCLER REAL-TIME PCR
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 479)
B Kabamba-Mukadi, J Ruelle, M Bodeus and P Goubau
We have developed a fast, sensitive and specific assay which enables the monitoring of HIV-1 proviral load.
480 CELLULAR HIV-DNA LOAD PREDICTS THE OUTCOME OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART)
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 480)
A Hatzakis1, G Touloumi1, N Pantazis1, C Anastassopoulou1, O Katsarou2, A Karafoulidou2, J J Goedert3 and LG Kostrikis1
The half-life of HIV DNA load was found to be 7.9 months and 59 months for patients with SVR and VFL, respectively (β0.036). These data suggest that cellular HIV DNA load is a marker of virological rebound in patients with initial viral response and it can reliably predict the long-term success of HAART.
481 TOTAL LYMPHOCYTE COUNTS (TLC) IS A POOR SURROGATE FOR CD4 COUNTS AMONGST ASYMPTOMATIC HIV INFECTED PATIENTS IN RESOURCE-LIMITED SETTINGS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 481)
A Mane1, A Patel2, S Pujari1, N Gupte3, J Patel2, K Patel2, S Bhagat1 and A Vashsihtha1
TLC is not a useful marker to predict CD4 counts amongst asymptomatic HIV-infected individuals in India, thus validating the WHO guidelines. Other factors like age, gender and haemoglobin also needs to be considered to enhance accuracy of TLC to predict CD4 counts.
482 REGIONAL METABOLITE ALTERATIONS IN THE BRAIN OF HIV-INFECTED ADULTS. A 31PHOSPHORUS-MR SPECTROSCOPIC IMAGING STUDY AT HIGH MAGNETIC FIELD
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 482)
EZ Kovacs1, WJ Chu2, JA den Hollander3, BA Bush4, LB Nabors5, MJ Kilby6, FC Kinney4, BJ Shelton7, S Hartley8, A Meidinger8 and DJ Benos1
The reduction of membrane phospholipid PDE/ATP is known to correlate with the degree of demyelinisation in degenerative cerebral disorders and may contribute to cognitive decline in HIV. Elevated PME/ATP represents elevated anabolic activity which probably corresponds to astrocyte proliferation. 31P-MR spectroscopy implicates the temporal lobe, occipital lobe, basal ganglia, and cerebellum as the brain regions most affected by the metabolic changes in HIV patients.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 52.19PO - Poster
IL-2
483 HIGH-AFFINITY RECEPTOR-SPECIFIC IL-2-ANALOGUE INDUCES CD25 EXPRESSION AND PROLIFERATION OF UNSTIMULATED HUMAN T CELLS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 483)
L Matthews, S Chapman, R Davey, HC Lane and I Sereti
BAY 50-4798 in vitro led to dose-dependent upregulation of CD25 and proliferation of freshly isolated PBMC of both HIV– and HIV+ donors, at a lower degree compared to equivalent doses of aldesleukin. The BAY 50-4798 effect on CD25 expression and proliferation showed selectivity for CD4 compared to CD8 and NK cells.
484 PHARMACOKINETICS OF SUBCUTANEOUS BAY 50-4798, A RECOMBINANT IL-2 SELECTIVE AGONIST, IN CYNOMOLGUS MONKEYS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 484)
CML Tseng, P Lum, A Fleser, M Boes, B Zhao, L Neyer, T Reynolds and E Cheung
Subcutaneous BID injections of BAY 50-4798 in 5-day cycles resulted in predictable, dose-proportional pharmacokinetics and negligible accumulation. These data, combined with the promising safety profile reported previously from this study, indicate that BID SC injection of BAY 50-4798 in 5-day cycles warrants further investigation as a treatment modality for HIV infection.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 52.20PO - Poster
Therapeutic Vaccination
485 IMMUNIZATION WITH RECOMBINANT TAT (R-TAT) TOXOID VACCINE DOES NOT PREVENT VIRAL REBOUND AFTER TREATMENT INTERRUPTION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 485)
M Hildebrand, K Kabeya, P Hermans, S De Wit, B Poll and N Clumeck
Neutralizing antibodies and cellular responses induced by r-Tat toxoid vaccine is not sufficient to control viral replication after interruption of HAART in both CHI and PHI patients. 1. P Hermans et al. Safety and immunogenicity of an HIV-1 Tat toxoid vaccine in HIV-1 infected volunteers on HAART. CROI 2003, Boston. Abstract #1–16.
486 5-YEAR EVALUATION OF A THERAPEUTIC VACCINE (HIV-1 IMMUNOGEN) ADMINISTERED WITH ANTIRETROVIRALS IN PATIENTS WITH HIV CHRONIC INFECTION: INDUCTION OF LONG-LASTING HIV-SPECIFIC CELLULAR IMMUNITY THAT IMPACT ON VIRAL LOAD
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 486)
E Fernandez-Cruz, J Navarro, S Moreno, B Clotet, E Bouza, JM Peña, J Pérez Molina, D Podzamczer, R Rubio, I Ocaña, F Pulido, C Rodriguez-Sainz, J Carbone, J Gil, ML Abad, L Díaz, C Cantó, P Viciana, JA Maradona, R Blazquez, C Barros, C Quereda, E Ferrer, A Jou, G Sirera, M Diaz, F Lopez, JM Gatell and J Gonzalez-Lahoz, for the STIR-2102 TEAM
The study shows that TI induces a strong HIVspecific immune response in HIV+ individuals, regardless of previous ART treatment, a decrease of aberrant immune system activation and a positive impact on controlling virus.
487 DEFECTIVE DC FUNCTION IN HIV-INFECTED PATIENTS RECEIVING EFFECTIVE HAART: NEUTRALIZATION OF AUTOCRINE IL-10 PRODUCTION PARTIALLY RESTORES CD4 T-CELL PROLIFERATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 487)
C Carbonneil1, V Donkova-Petrini1, H Saidi1, A Aouba2 and L Weiss1,2
In HIV-infected patients, DCs whether generated in the presence of GM-CSF and IL-4 or GM-CSF and IFN-α exhibit intrinsic defect in inducing CD4 T cell responses. This may be related in part to an autocrine IL-10 production. The present study emphasizes the relevance of modulating IL-10 production to enhance specific CD4 T-cell responses for immune intervention in HIV infection.
488 ELICITING ANTIGEN-SPECIFIC CELLULAR IMMUNE RESPONSES USING DENDRITIC CELLS AS A FIRST STEP TOWARDS THERAPEUTIC IMMUNOTHERAPY IN AIDS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 488)
G Van den Bosch1, P Ponsaerts1, M Lenjou1, G Nijs1, D Van Bockstaele1, V Van Tendeloo1, G Vanham2 and Z Berneman1
We assessed the allogeneic and autologous T-cell stimulatory capacity of monocyte-derived DCs in HIV+ patients and evaluated the possibility of inducing tat and gag specific cellular immune responses by using antigen-loaded autologous DCs in HIV-1-infected patients.
489 IMMUNOLOGICAL AND VIROLOGICAL CHANGES IN HIV-1 INFECTED SUBJECTS UNDERGOING LEUKAPHERESIS: IMPLICATION FOR THERAPEUTIC IMMUNIZATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 489)
MR Boulassel1-2, G Spurll2, D Rouleau3, C Tremblay3, RP Sekaly4 and JP Routy1-2
No changes in viral load form pre-leukapheresis level in treated or untreated subjects were detected at any time points. We conclude that leukapheresis in HIV-1-infected subjects is safe and induces a transient increase in the absolute and percentage of CD4+ cell count without enhancing viral replication.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 52.21PO - Poster
Other Immune-based Therapies
490 CORRELATION BETWEEN PRE-HAART LEVELS CIRCULATING IL-7 BEFORE HAART AND CD4 RESTORATION FOLLOWING THERAPY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 490)
JH Colle1, S Beq1, A Fontanet1, MT Rannou2, JF Delfraissy2 and J Thèze1
IL-7 is necessary both for thymopoiesis and for the homeostatic regulation of T lymphocytes in the periphery. A negative correlation has been reported in HIV patients between the IL-7 plasma levels and CD4 count. Post-HAART IL-7 levels tend to normalize as the CD4 count increases. Thus, IL-7 production may be part of a compensatory feedback loop in response to CD4 depletion.
491 IL-2 FAILED TO BOOST CD8 RESPONSES IN RHESUS MACAQUES WHILE IL-15 BOOSTED ANTIGEN-SPECIFIC MEMORY RESPONSES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 491)
F Villinger, R Miller, AE Mayne, P Bostik, JB Sundstrom and AA Ansari
Using tetanus toxoid (TT) and live attenuated influenza (Flu) immunization of rhesus macaques as model immunogens, the effect of IL-2 and IL-15 on the generation and maintenance of antigen-specific memory T cells was evaluated following primary and secondary immunization. While administration of IL-2 following primary immunization enhanced TT specific CD4 and Flu-MP specific CD8 effector responses, Flu-specific CD8 memory responses were no different from cytokine non-treated monkeys.
492 PEGYLATED INTERFERON ALPHA STIMULATES THE ANTI-HIV IMMUNE RESPONSE AND PREVENTS VIRAL REBOUND DURING STRUCTURED TREATMENT INTERRUPTIONS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 492)
D Emilie1, R Krzysiek1, V Godot1, L Adalid1-2, M Burgard2, G Chene3, P Galanaud1, D Sereni4, C Rouzioux2 and the PRIMOFERON/ASTI (ANRS 086) Study Group
Altogether, these findings show that PEG-IFNα stimulates the anti-HIV immune response emerging during primary HIV infection and prevents viral rebound associated with STI in such patients. A larger and randomized study is under progress to confirm that such a therapeutic strategy is able to maintain undetectable HIV RNA in some patients after sustained interruption of HAART.
493 EFFECT OF INTERLEUKIN-15 ON IFN-γ AND β-CHEMOKINE PRODUCTION BY NATURAL KILLER CELLS IN HIV-INFECTED INDIVIDUALS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 493)
G Forcina, G d’Ettorre, A Salvati, M Carnevalini, L Scorzolini, CM Mastroianni and V Vullo
Interleukin (IL)-15 plays an important role in the development, survival and function of natural killer (NK) cells. NK cells from patients with untreated HIV infection have several number and functional defects that are recovered, at least in part, during HAART. Immunotherapeutic strategies for chronic HIV infection suggest that IL-15 may represent a potential candidate for cytokine treatment in combination with HAART. We evaluated the role of IL-15 in priming for IFN-γ production by NK cells from HIV-infected patients receiving HAART. We also studied the production of MIP-1β and RANTES by IL-15-stimulated NK cells.
494 SHOULD WE TREAT HEALTHY HIV PATIENTS WITH PREDNISOLONE?
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 494)
A Ulmer, M Mueller and B Frietsch
It seems possible to reach a marked prolongation of time without HAART through low-dose glucocorticoid therapy.
495 SPECIFIC gp120ASE ANTIBODIES INDUCED BY COVALENT IMMUNIZATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 495)
S Paul1, S Planque1, YX Zhou1, S Karle1, H Taguchi1, G Bhatia1, Y Nishiyama1, M Salas2 and C Hanson2
These findings are the first indication that antigen-specific proteolytic Abs can be synthesized on demand by covalent immunization.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 52.22PO - Poster
HIV Vaccine Strategies
496 AN EFFECTIVE STRATEGY TO INDUCE BROADLY CROSS-REACTIVE PRIMARY ISOLATE NEUTRALIZING ANTIBODY RESPONSES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 496)
IK Srivastava, E Kan, V Sharma, Y Sun, JB Ulmer and SW Barnett
Efforts are underway to identify a minimal CD4 domain capable of triggering the conformational change in the HIV Env and evaluate its ability to induce antibody responses of similar quality.
497 CYTOTOXIC T-LYMPHOCYTE INDUCTION FOLLOWING LIPOPEPTIDE VACCINATION CORRELATES WITH DELAY OF DISEASE ONSET IN SIVmac251 CHALLENGED RHESUS MACAQUES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 497)
Z Coutsinos1, P Villefroy1, F Letourneur1 L Mortara1, H Gras-Masse2, C Beyer3, AM Aubertin3, A Venet1, JG Guillet1 and I Bourgault-Villada1
Although all vaccinated macaques became infected after SIV challenge, a correlation was evidenced between the presence of CTL induced by lipopeptide vaccination and the delay of disease onset. Responding animals (70%) were AIDS-free for an average of 29 months (SD=9.42). On the contrary, macaques that did not develop CTL responses following vaccination (7/24) had a significantly lower life span with an average onset of AIDS symptoms at 14.86 months (SD=7.2) (P<0.001). Thus, SIV-lipopeptide vaccination induced CTL responses are correlated with delay of disease onset in SIV-infected macaques.
498 VACCINE DESIGN STUDY IN CÔTE D'IVOIRE (WEST AFRICA): CROSS REACTIVE HIV-1 CLADE B CD8+ T LYMPHOCYTES IN PATIENTS INFECTED WITH HIV-1 SUBTYPE CRF02-AG
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 498)
A Inwoley1, P Recordon-Pinson2, M Dupuis3, J Gaston3, A Minga4, B Masquelier2, J Choppin3, F Rouet1, H Fleury2, JG Guillet3, M Andrieu3 and ANRS 1220 PRIMOCI group
This study shows that people infected with HIV-1 subtype CRF02_AG can generate cross-reactive CD8+ T cell responses against HIV-1 subtype B. Furthermore, there is no major variation in immunodominant regions corresponding to HIV clade B vaccine candidates in particular lipopeptide vaccines, currently tested in France (ANRS Vac04, Vac10, Vac12). These promising results allow us to consider a vaccine trial in Côte d’Ivoire using HIV clade B lipopeptides. We plan to clone some variants of nef gene for some patients to confirm the weak variation in this immunodominant region.
499 BREADTH OF CD8+ T LYMPHOCYTE RESPONSES INDUCED IN RHESUS MACAQUES VACCINATED WITH NEF AND GAG LIPOPEPTIDES IS DEPENDENT ON ROUTE OF IMMUNIZATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 499)
Z Coutsinos1, P Villefroy1, H Gras-Masse2, JG Guillet1 and I Bourgault-Villada1
Our results suggest that breadth of cellular immune responses is affected by lipopeptide administration route, with a better overall response for ID inoculated antigens.
500 COMPARISON OF DIFFERENT HETEROLOGOUS PRIME-BOOST HIV-1/SIV VACCINE REGIMENS INCLUDING RECOMBINANT DNA, SFV, MVA AND PROTEINS: IMMUNE RESPONSES AND VIRAL LOAD IN CYNOMOLGUS MACAQUES AFTER INTRARECTAL CHALLENGE WITH SHIV-BX08
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 500)
A Mörner, P Liljeström, B Wahren, R Thorstensson and G Biberfeld
The objective of this study was to compare the immunogenicity and protective capacity against SHIV in cynomolgus macaques of three different heterologous prime-boost HIV-1/SIV vaccine regimens. The first group of six monkeys received two DNA immunizations followed by two MVA immunizations. In the second group the DNA was replaced by SFV. The third group was given two DNA followed by two protein/ODN immunizations.
501 PRIMING WITH DNA AND RECOMBINANT GM-CSF FOLLOWED BY PROTEIN CpG-ODN BOOST INDUCES STRONG ANTI-HIV-1 ENVELOPE IMMUNE RESPONSES IN MICE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 501)
K Ljungberg, E Rollman, B Zuber, A Kjerrström Zuber, J Hinkula and B Wahren
We thus developed a prime-boost regimen that induces strong neutralizing anti HIV-1 gp160 humoral and cellular immune responses. Ultimately, this may permit induction of stronger immune responses to the HIV-1 envelope gene in patients.
502 SEQUENCE VARIATION OF THE NEF GENE IN GENETICALLY IMMUNISED HIV-1 INFECTED PATIENTS WITH ELICITED CTL RESPONSES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 502)
S Aleman, T Leitner, M Liu, M Birk and B Wahren
An important role for cytotoxic T-lymphocytes (CTL) in containing HIV infection has been shown in many studies.
503 IMMUNOGENIC HIV CLASS I AND CLASS II T-CELL EPITOPES FOR THE GAIA CROSS-CLADE HIV VACCINE
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 503)
H Sbai1, EA Bishop1, W Martin 2, M Lally3, KH Mayer3 and AS De Groot1-2
These HLA class I and class II T cell epitopes will be included in the GAIA world clade HIV-1 vaccine along with previously identified HLA class I T cell epitopes. These data confirm the utility of bioinformatics tools to select and design novel ‘immunogenic consensus sequence’ T cell epitopes for our globally relevant GAIA vaccine against HIV infection.
504 CELL-BASED VACCINATION: RATIONALE FOR THE USE OF CELLS CO-EXPRESSING HIV ENV gp120 AND HLA CLASS I Cw4 MOLECULES FOR THE INDUCTION OF NEUTRALIZING ANTIBODIES
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 504)
D Zipeto1, A Cosma2, R LeGrand3, V Erfle2, AG Siccardi4 and A Beretta4
Induction of antibodies capable of neutralizing different clades of HIV has so far proved difficult. The major obstacle in the induction of neutralizing antibodies is the construction of Env molecules expressing conformational determinants which are not expressed on conventional soluble recombinant Env. A possible approach to solve this problem is the use of immunogens which express, together with Env gp120/160, also cell-derived molecules that are associated with Env either during the viral entry process (i.e., CD4 and CCR5) or during the process of budding of HIV from the cells.
505 PRECLINICAL EVALUATION OF INDIAN HIV-1 SUBTYPE C VACCINE CONSTRUCTS IN MICE AND MONKEYS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 505)
P Seth1, A Arora1, P Chugh1, S Kumar1, VVSP Prasad1, M Vajpayee1 and AJ Rao2
Molecular epidemiology of HIV strains circulating in India has indicated that HIV-1 subtype C is the predominant virus clade. Therefore, it is imperative that a vaccine based on the local circulating subtype should be designed and tested for their immunogenicity in mice and non-human primate models.
| July 2003 | Monday, July 14th to Wednesday, July 16th
Session 52.23PO - Poster
Vectors and Adjuvants
506 HUMAN FOAMY VIRUSES (HFVs): POTENTIAL VECTORS FOR HIV VACCINE AND GENE THERAPY
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 506)
D Hardy1, C Liu1, Y Xie2, T Folks3 and I Chen2
A replication-competent, transducing vector, FOV-gag, expresses both HIV-1 p17 and p24 mRNA as well as HIV-1 p24 antigen for 21 days following infection Its in vivo transducing and immunogenic properties are being tested in a mouse model. HFV vectors carrying HIV-1 inserts have potential use as HIV vaccine and gene therapy applications.
507 DIFFERENTIAL EFFECTS OF CpG ODN ON ANTIGEN SPECIFIC RECALL RESPONSES BY T CELLS FROM HIV-INFECTED INDIVIDUALS AND HEALTHY DONORS] DIFFERENTIAL EFFECTS OF CpG ODN ON ANTIGEN SPECIFIC RECALL RESPONSES BY T CELLS FROM HIV-INFECTED INDIVIDUALS AND HEALTHY DONORS
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 507)
W Jiang, S Sieg, J Salkowitz, K Medvik, C Harding and M Lederman
Although CpG ODN enhances APC maturation in PBMC from healthy individuals it also has inhibitory effects on T cell proliferation responses. The inhibitory effects are probably related to antigen processing since CpG ODN enhances responses to superantigen. PBMC from HIV-infected individuals respond differently to CpG ODN with reduced APC maturation and enhanced proliferation to CMV, however, there is still inhibition of TT responses. Thus, the effects of CpG on proliferation responses are dependant on both HIV infection and on the nature of the antigen.
508 A SIMIAN REPLICATION-DEFECTIVE ADENOVIRUS MULTI-RECOMBINANT VACCINE TO SIV REV-ENV-GAG-POL
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 508)
BV Vingert, A Rodallec, R Le Grand, JG Guillet and A Venet
Only few T CD8 responses were observed after culture in seven monkeys. After the second immunization, the boost of the T CD8 response was moderated. A weak T CD4 proliferation response was also detected. Neutralizing Abs against adenovirus were detected after the first immunization but they were higher after the second injection of the recombinant adenovirus. After challenge with SIVmac, all monkeys were infected without specific control of the viral load. Used only, this multi-recombinant adenovirus could not induce the strong immune response to control a pathogenic strain of SIV.
509 CONTAINMENT OF SHIV 89.6P CHALLENGE BY EPITOPE-BASED DNA VACCINE PRIMING AND RECOMBINANT POXVIRUS BOOSTER IMMUNIZATION
IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd:(abstract no. 509)
AL Puaux1, R Legrand2, D Marsac1, P Earl3, B Moss3, Y Rivière4 and ML Michel1
We have previously reported that intramuscular injection of DNA expression vectors encoding the V3 domain of HIV-1 fused to the hepatitis B virus surface antigen (HBsAg) induced specific and strong humoral and cytotoxic responses to antigenic determinants of both virus in mice and non-human primates. We designed hybrid DNA constructs coding for HBsAg fused to antigenic domains of SHIV 89.6P Gag,