Single-dose nevirapine (sdNVP) is the most common option for the prevention of mother-to-child transmission (PMTCT) of HIV-1 in countries with limited resources, although it is considered as the minimal antiretroviral intervention in the 2006 WHO guidelines . However, the use of sdNVP induces viral resistance mutations with an estimated frequency at 4–8 weeks postpartum of about 35% in mothers and 50% in contaminated children . These mutations could compromise the virological response to the subsequent maternal or paediatric treatments that include nonnucleoside reverse transcriptase inhibitors (NNRTI), the main first-line treatment regimens in resource-limited settings , particularly in those initiating such treatment within 6 months after delivery [4,5]. In the current context of facilitated and rapidly increasing access to antiretroviral treatments, an effective, low-cost, easy-to-use, low-toxicity alternative or complement to sdNVP is thus needed for PMTCT. Tenofovir disoproxil fumarate (TDF) is the prodrug of tenofovir. It is highly effective in protecting newborn macaques against simian immunodeficiency virus infection given as short-course regimens and has no major toxicity in animal studies when given at higher doses for short courses and lower doses for more prolonged courses [6,7]. Viral resistance to TDF is rare and takes a long time to appear when this drug is administrated as a part of a fully suppressive treatment . Emtricitabine (FTC) has the same efficacy, tolerance and resistance profile as lamivudine (3TC), which is already used for PMTCT , and a coformulation of TDF/FTC is available. The safety and efficacy of TDF/FTC combined with nevirapine (NVP) or efavirenz was deemed satisfactory in adults, and it has been recommended by WHO since June 2005 as a compound to include in first-line treatment regimens . In a recent randomized trial conducted in Zambia, about 400 women were administered a single-dose combination of 300 mg of TDF and 200 mg of FTC at the onset of labour together with a single dose of 200 mg of NVP . The combination of TDF/FTC was well tolerated, and the occurrence of NVP viral resistance mutations was halved at 6-week postpartum but remained substantial (12%). The few available data argue for further investigation of optimal administration schemes of the fixed-dose combination of TDF/FTC for PMTCT. The Agence Nationale de Recherches sur le Sida et les hépatites virales (ANRS) 12109 TEmAA (Tenofovir Emtricitabine in Africa and Asia) trial thus aimed to evaluate the safety of a short course of TDF/FTC in HIV-1-infected pregnant women and their newborns. The frequency of resistant virus to these drugs was also assessed.
Design and intervention
The TEmAA trial is a phase I/II, multicentre, open-label clinical trial to be conducted in two sequential steps in Abidjan (Côte d'Ivoire), Soweto (South Africa) and Phnom Penh (Cambodia). In the first step, now completed and reported here and elsewhere [11,12], two tablets of 300 mg of TDF/200 mg of FTC were administered to the mothers at the onset of labour or 4 h prior to a Caesarean section and continued as one tablet per day during 7 days postpartum. The double intrapartum dose has been demonstrated to result in concentrations comparable to those achieved among HIV-infected nonpregnant adults receiving chronic therapy with 300 mg of TDF daily . Postpartum prophylaxis was given to comply with WHO guidelines to avoid NVP resistance . In the second step, TDF and FTC will also be administered to the newborns as a single dose.
Women received, in addition to study drugs, a standard PMTCT regimen with 300 mg of zidovudine (ZDV) twice daily from their enrolment (28–38 weeks of gestation) and 200 mg of sdNVP at the onset of labour according to the WHO guidelines . Children received a sdNVP (2 mg/kg) on the first day of life and 4 mg/kg of ZDV syrup every 12 h for 7 days after birth. The use of NVP as a backbone PMTCT drug in mothers and children was considered necessary in this study because the efficacy of TDF/FTC for PMTCT is still unknown. Cotrimoxazole prophylaxis against opportunistic infections was prescribed in women with a CD4 cell count of less than 350 or less than 200 cells/μl, according to national guidelines. Women were advised to choose either replacement feeding from birth or exclusive breastfeeding with weaning from at least 4 months of life. They were given support, including free provision of equipment and supplies, up to 12 months postpartum.
Pregnant women were enrolled if they were positive for HIV-1 or HIV-1/HIV-2 infection, aged 18 years or over on the day of enrolment. Their gestational age was calculated on the basis of the date of last menstruation period or, if not available, on ultrasound scan . They had to be naive to any antiretroviral drug (including antiretroviral PMTCT prophylaxis in previous pregnancies) with no indication for antiretroviral treatment according to WHO guidelines : clinical stage 1, 2 and CD4 cell count of at least 200 cells/μl or stage 3 and CD4 cell count of at least 350 cells/μl. They were asked to sign an informed consent form (as well as the father of the child to be born in Abidjan and Phnom Penh) and to agree to deliver in a dedicated hospital setting and stay for at least 72 h afterwards. In addition, they had to fulfil five biological criteria: haemoglobin at least 8 g/dl, blood creatinine less than three times the upper limit of normal values, creatinine clearance at least 50 ml/min, transaminases [alanine aminotransferase (ALAT) or asparatate aminotransferase (ASAT)] less than five times the upper limit of normal values and neutrophils at least 750/mm3.
The women and their newborns underwent clinical examination at screening, enrolment, prenatal consultations, delivery or birth and at 3, 7, 15, 28, 45 and 60 days after delivery or birth. Maternal renal tubular function (blood creatinine and urinary glucose), hepatic function (transaminases and gamma-GT), bone metabolism (blood phosphate) and blood glucose were checked at screening or enrolment and 28 days. Full blood, CD4 cell and platelet counts were assessed prior to trial screening, then at 2 and 28 days. Infant renal tubular function (urine beta-2 microglobulin, blood creatinine and urinary glucose), haematologic function (full blood count and platelet count) and hepatic function (transaminases and gamma-GT) were checked at 28 days.
A serious adverse event (SAE) was defined as death, life-threatening event, hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, event judged potentially serious by the investigator or requiring intervention to prevent progression to one of the above mentioned conditions or congenital abnormality in the offspring of women who received the trial drug. A grade 3 or 4 biological or clinical adverse event (according to the 2003 ANRS rating scale for the seriousness of clinical manifestations and abnormal laboratory findings for mothers and the 1994 Pediatric AIDS Clinical Trial Group age-specific scale for children) was also considered as an SAE.
The local virology laboratories processed plasma HIV-1 RNA viral load using the generic ANRS quantitative real-time PCR in Abidjan and Phnom Penh  and Roche Amplicor v1.5 (Roche Molecular Systems, Inc., Branchburg, New Jersey, USA) in Soweto, with a threshold limit for detection of 2.6 log10 (400 copies/ml). The same technique was used for a given patient throughout the course of the trial. Maternal viral load was measured at enrolment, 2 and 28 days postpartum. In the case of undetectable viral load at enrolment with the local techniques, the Cobas TaqMan Roche quantification test (Roche Diagnostics, Meylan, France) was also performed. Infant plasma viral load was measured for diagnosis on 3, 28 and 45 days. HIV-1 RNA was used for the diagnosis of infection in the babies . In-utero HIV infection was defined as detectable viral load at 3 and 28 days. Peripartum infection was defined by an infant viral load not detectable at 3 days but detectable at 28 and 45 days.
Genotypic resistance tests were performed on plasma samples collected at 28 days in mothers and infected children using the consensus technique of the AC11 ANRS Resistance group . All laboratories participate in the annual ANRS quality assurance programme . Prevalence of mutations associated with transmitted drug-resistant HIV-1 was analysed using the 2007 International AIDS Society list of mutations. Interpretation of drug resistance was performed using the ANRS 2007 algorithm v16 . Possible resistance was considered as resistance.
Phylogenetic relationships of the reverse transcriptase were estimated from sequence comparisons with previously reported representatives of group M subtypes and circulating recombinant forms (CRFs) for which sequences are available in the HIV database. The reverse transcriptase nucleotide sequences were aligned using Clustal W (version 1.7) with minor manual adjustments . Phylogenetic trees were constructed with the Neighbour-joining method, and reliability of the branching orders was implemented by Clustal W using the bootstrap approach .
The protocol was approved by the Ethics Committee of each country (Côte d'Ivoire, Cambodia and South Africa) as well as by the Medical Control Council of South Africa. This study is registered with ClinicalTrials.gov number NCT00334256.
Biological and clinical variables were described using the median and interquartile range (IQR) or proportion, according to the type of variable. Median viral load values at enrolment and 48 h postpartum were tested for differences using the Wilcoxon test for paired samples (α = 0.05). The proportion of children infected at 3 or 28 days or both, then confirmed at 45 days, and the proportion of SAEs related to the trial drug were estimated with their 95% confidence interval (CI). The probability of HIV-free survival at 45 days of life was estimated using the Kaplan–Meier method. The proportion of individuals infected that showed ZDV, NVP, TDF or FTC resistance at day 2/day 3 and/or day 28 was estimated, and their resistance patterns were described. ACCESS, version 2003 (Microsoft Corporation, Redmond, Washington, USA) and SAS, version 9.1 (SAS Institute, Inc, Cary, North Carolina, USA) software were used for data management and statistical analysis, respectively.
Role of the funding sources
The French ANRS sponsored the trial and was involved in the protocol development and data interpretation. The European and Developing Clinical Trials Partnership provided additional financial support to the Ivoirian site but did not play any role in the study. The corresponding author had full access to all study data and had the final responsibility for the decision to submit for publication.
Characteristics of the patients
Forty-two women were enrolled (19 in Abidjan, 12 in Phnom Penh and 11 in Soweto) between November 2006 and July 2007. Four women delivered in an off-protocol facility in Soweto, all of them prematurely at less than 37 weeks of gestation. They did not receive TDF/FTC and discontinued the protocol follow-up. Among the 38 remaining women, none of them was eligible for antiretroviral treatment, with a median CD4 cell count of 450 cells/μl (IQR = 324–584); 29 (76%) of them were at WHO clinical stage 1. Median age was 27 years (IQR = 23–30), and median gestational age at enrolment was 32.5 weeks of amenorrhoea (IQR = 30–34). They had a history of two previous pregnancies in median (IQR = 1–3).
All 38 women received antenatal ZDV for a median duration of 47 days before delivery (IQR = 29–73), intrapartum sdNVP along with TDF/FTC and 1 week of TDF/FTC. The median time interval between the first TDF/FTC administration and delivery was 4.9 h (IQR = 3.3–8.2; minimum 0.5 and maximum 19.7 h). Twelve women (31.6%) delivered within 4 h after the first study drug administration and the remaining in the first 24 h. The first postpartum drug administration was missed for one woman, two women took two additional tablets of TDF/FTC on their own initiative and one received the study drugs for 8 days postpartum.
Twenty-four women delivered vaginally, seven by elective caesarean section (six in Soweto and one in Phnom Penh) and seven by emergency caesarean section (six in Abidjan and one in Phnom Penh). Thirty-nine children were born alive, including one pair of twins. Six had low birth weight (<2500 g), four in Abidjan and two in Soweto. Neither stillbirth nor congenital malformation was reported. All babies received ZDV and sdNVP as per the protocol. Three babies were breastfed at birth, all in Abidjan; the other babies had formula feeding only. In 30 women with rupture of membranes before delivery, the median time was 29 min (IQR = 5–287). Sixteen women experienced obstetrical complications, including six premature ruptures of membranes, four dystocia, three delivery/postpartum haemorrhage (one associated with dystocia), one acute foetal distress and three indications for episiotomy/repair.
Nine SAEs occurred in women (23.7%; 95% CI = 11.4–40.3), six in Abidjan (31.6%) and three in Phnom Penh (25.0%). All these events were biological and occurred after delivery, three grade 3/4 anaemia at 48 h postpartum, five grade 3/4 neutropenia associated or not with grade 3 leucopoenia (three at 48 h postpartum and two at 7 days) and one grade 3 elevation of liver enzymes at 28 days in a woman coinfected with hepatitis C virus (HCV).
All these SAEs had resolved at 28 days except for the elevation of liver enzymes, which resolved at 5 months postpartum. Two women had CD4 cell count of less than 200 cells/μl, one at 7 days and one at 28 days, thus becoming eligible for an antiretroviral treatment for their own health . At 28 days, the median blood phosphorus level was 1.19 mmol/l (n = 37; IQR = 1.02–1.28; minimum, 0.82; maximum, 1.50), and the creatinine clearance was 132 ml/min (n = 37; IQR = 115–160; minimum, 91; maximum, 290).
Eleven SAEs occurred in babies (28.2%; 95% CI = 15.0–44.9), consisting of two biological events and nine clinical events (Table 1). All these babies were formula fed. Two of the clinical SAEs occurred in the two children infected with HIV in utero. Three infants died during the protocol follow-up (one in Phnom Penh and two in Abidjan) and one 7 months after birth (in Abidjan). The overall Kaplan–Meier HIV-free survival probability of the neonates 45 days after birth was 89.7% (95% CI = 73–96).
Two babies had grade 3 transient anaemia detected at 28 days, 14 had grade 1 anaemia and 12 had grade 2 anaemia. No serious neutropenia were reported during the protocol follow-up, but two babies had grade 1 and two had grade 2 neutropenia. Seven children had grade 1 ASAT and ALAT, and 13 additional children had grade 1 ASAT only. At 28 days, the median blood creatinine in 36 children was 18.0 μmol/l (IQR = 17.7–24.0; minimum, 17.7; maximum, 44.2), whereas the urine beta-2 microglobulin was 0.61 mg/l (IQR = 0.16–1.70; minimum, 0.02; maximum, 17.96). The observed SAEs were not considered to be related with the TDF/FTC administration (mothers) or exposure (infants).
HIV RNA kinetics
Viral load was 2.6 log10 or less (<400 copies/ml) in four women at enrolment [n = 37; 11%, two in Abidjan (subtypes CRF02-AG and A) and two in Phnom Penh (subtype CRF01-AE)], eight (n = 38; 21%) at 2 days and seven (n = 38; 18%) at 28 days. Among 33 women (one missing data) with a viral load of more than 2.6 log10 at enrolment, the viral load decreased at 2 days by a median of −0.90 log (IQR = −1.31, −0.39) (P < 10−4) and returned to the initial level at 28 days (Fig. 1).
The viral load was undetectable in all children at all times except for two babies (5.1%; 95% CI = 0.6–17.4), an Ivoirian and a South African one, who had detectable viral load at 3 days (3.80 log10 and 4.81 log10) and 28 days (6.02 log10 and 5.82 log10), suggesting an in-utero HIV infection. The Ivoirian child died at 55 days of life (Table 1). The two infected children were born from mothers with a high viral load at enrolment (>6 log10) but a CD4 cell count of more than 250 cells/μl.
In 37 women tested at 28 days (one not amplifiable), no TDF, FTC, NVP or ZDV viral resistance mutation was found (upper limit of the 95% CI = 9.5%). The phylogenetic analysis (Fig. 2) showed that, in Abidjan, 15 women harboured CRF02-AG viruses, three an A virus and one a CRF06 virus. In Phnom Penh, the 11 women had CRF01-AE viruses, and all those in Soweto had C viruses. The infant infected with HIV in Abidjan harboured a CRF02-AG strain and the one infected in Soweto, a C strain. None of them had viral resistance to the four drugs at 28 days.
The first step of the ANRS 12109 trial showed that the TDF/FTC combination, administered at the onset of labour and during 7 days postpartum, was well tolerated by the mothers and the exposed newborns. In addition, no peripartum HIV transmission was diagnosed, and viral resistance was neither detected at 28 days in the mothers nor in the infants with in-utero infection.
The TDF/FTC combination did not induce unexpected SAEs. Maternal anaemia was probably related to obstetrical complications (two delivery haemorrhages and one emergency caesarean section), and neutropenia was related to cotrimoxazole or ZDV intake. A potential synergistic effect of this TDF/FTC short course on ZDV haematological toxicity was unlikely but could not firmly be excluded on such a small number of patients. The elevation of liver enzymes occurred in a patient with HCV coinfection. Neonatal clinical SAEs had an infectious background in eight patients. Severe and early neurological symptoms remained unexplained, as a specific evaluation could not be performed on site. Our results are consistent with the few studies reporting data on the use of TDF during pregnancy. In the Zambian trial, the combination of 300 mg of TDF and 200 mg of FTC administered as a single dose at the onset of labour was also well tolerated . As a larger single dose at the onset of labour, 600 mg of TDF did not induce any clinically significant adverse event in mothers or infants . As a part of a triple antiretroviral therapy among Ugandan pregnant women, TDF was also well tolerated with no congenital malformation attributed to the in-utero drug exposure . A similar observation was recently reported in the United States .
No peripartum transmission was reported although the small number of patients does not allow for an accurate comparison with rates reported in other studies in women not requiring antiretroviral treatment for their own health. The peripartum transmission rate was 3.5% in Ivoirian women having received a short course of ZDV or ZDV/3TC and sdNVP , 1.3% in South African women having received sdNVP and either a placebo or a 4/7-day short course of 3TC/ZDV postpartum . However, it was 6.9% in the Zambia trial using sdNVP together with sdTDF and FTC but at a lower dose than in the present trial .
No viral resistance to NNRTIs and nucleoside reverse transcriptase inhibitors (NRTIs) was observed. It was expected for TDF, for which resistance acquisition is rare and requires a long duration of exposure . Regarding FTC, this finding was also expected as in the Treatment Option Preservation Study in which no NRTI resistance was detected  and because the occurrence of such resistance is related to the duration of drug exposure [27,28]. Of particular interest, no viral resistance to TDF and NVP was observed, even for the C subtype viruses, for which the selection of such resistant viruses was more often described compared to other subtypes [29,30]. Providing 7 days of postpartum antiretroviral exposure with TDF/FTC immediately after sdNVP and TDF/FTC combination seems to extend the suppression of viral replication, avoiding a postpartum exposure to NVP monotherapy and thus minimizing the risk of NNRTI resistance, as already demonstrated for the 3TC/ZDV combination [2,26,27] or for TDF/FTC . In this last study, the residual NVP resistance rate in the intervention group was still significant at 12% (95% CI = 7.2–17.3). On the contrary, no resistance was observed in the present study (upper limit of 95% CI = 9.5%). In addition, standard genotyping techniques have been used and have probably failed to detect resistance mutations present at frequencies lower than 20% . Sensitive techniques could have investigated resistant minority variants although their clinical relevance has not been demonstrated so far. In addition, in the context of PMTCT, a recent brief report showed that repeated use of sdNVP to prevent HIV transmission does not appear to influence NVP resistance . Moreover, prior use of sdNVP for PMTCT does not appear to compromise the effectiveness of sdNVP in subsequent pregnancies [33,34]. Some studies have suggested that previous exposure to sdNVP may compromise future antiretroviral therapy in women receiving a NNRTI-based regimen if therapy is started within 6–12 months of sdNVP administration [5,35]. But other studies demonstrated that when antiretroviral treatment was initiated more than 12 months after the intervention for PMTCT of HIV, NVP exposure was not associated to virological failure .
In conclusion, the results of this first step of the TEmAA trial are extremely encouraging for continuing human research on PMTCT with the TDF/FTC combination. Two tablets of TDF/FTC given at the onset of labour were well tolerated for women and HIV-exposed children. In addition, this exploratory analysis suggests that this strategy deeply reduces the risk of NVP viral resistance, and further evaluations could be considered to explore this combination as an alternative to the ZDV/3TC postpartum prophylaxis ; for example, in women with severe postpartum anaemia. Compared with this latter regimen, administered twice a day, the TDF/FTC combination given once daily represents a simplified strategy. This trial also evaluated the pharmacokinetic properties of the study drugs, presented elsewhere [11,12]. The second step of the TEmAA trial will now confirm these safety and virology data and will investigate whether the pharmacokinetics of the TDF/FTC combination, also administered to the newborns as a single dose, allows for its use without sdNVP for PMTCT of HIV-1.
We acknowledge the French ANRS for sponsoring the trial, as well as the European and Developing Country Clinical Trials Partnership (EDCTP) for their additional financial support. Didier K. Ekouevi was an EDCTP Senior fellow (2005–2007).
We greatly thank the local investigators and their staff in the Formations Sanitaires Urbaines de Youpougon-Attié and Abobo-Avocatier and the Centre Hospitalier Universitaire de Yopougon in Abidjan, in the Calmette Hospital and Pasteur Institute in Phnom Penh and in the Perinatal HIV Research Unit and Lesedi Clinic in Soweto. We also thank the women and infants who agreed to participate in the trial. We acknowledge Gilead Sciences for providing the study drugs. Special thanks to Brigitte Bazin and Jean-François Delfraissy (ANRS), Aldo Trylesinski and James Rooney (Gilead) for their continuing support.
The authors' contributions are the following (all authors have read and approved the final version): Elise Arrivé: protocol development, coordination and monitoring of the study, data analysis, writing of the manuscript; Marie-Laure Chaix: protocol development, virological analysis, writing of the manuscript; Eric Nerrienet: protocol development, coordination of the Cambodian site, virological analysis, review of the manuscript; Stéphane Blanche: protocol development, validation of safety data, review of the manuscript; Christine Rouzioux: protocol development, virological analysis, review of the manuscript; Patrick A. Coffie: Ivorian site monitoring, data collection, review of the manuscript; Sim Kruy Leang: protocol development, coordination of the Cambodian site, patients' care and data collection, review of the manuscript; James McIntyre: protocol development, coordination of the South African site, review of the manuscript; Divine Avit: Ivorian site monitoring, patients' care and data collection, review of the manuscript; Viseth Horm Srey: Cambodian site monitoring, data collection, review of the manuscript; Glenda Gray: protocol development, coordination of the South African site, review of the manuscript; Thérèse N'Dri-Yoman: protocol development, coordination of the Ivorian site, review of the manuscript; Alpha Diallo: safety data validation, review of the manuscript; Didier K. Ekouévi: protocol development, coordination of the overall study and the Ivorian site in particular, review of the manuscript; François Dabis: protocol development, coordination of the overall study, writing of the manuscript.
The TEmAA Study Group is constituted as follows:
Writing committee: Elise Arrivé (INSERM U897, ISPED, Université Victor Segalen, Bordeaux, France), Marie-Laure Chaix (Université Paris-Descartes EA 3620, Laboratoire de virologie, CHU Necker Enfants Malades, Paris, France), Eric Nerrienet (Laboratoire HIV/Hépatites, Institut Pasteur du Cambodge, Phnom Penh, Cambodia), Stéphane Blanche (Service d'Immunologie et Hématologie Pédiatrique, Hôpital Necker Enfants Malades, Université Paris-Descartes, Paris, France), Christine Rouzioux (Université Paris-Descartes EA 3620, Laboratoire de virologie, CHU Necker Enfants Malades, Paris, France), Patrick A. Coffie (Programme PAC-CI/ANRS, Abidjan, Côte d'Ivoire), Sim Kruy Leang (Service de Gynécologie-Obstétrique, Hôpital Calmette, Phnom Penh, Cambodia), James McIntyre (Perinatal HIV Research Unit (PHRU), University of the Witwatersrand, Soweto, South Africa), Divine Avit (Programme PAC-CI/ANRS, Abidjan, Côte d'Ivoire), Viseth Horm Srey (Laboratoire HIV/Hépatites, Institut Pasteur du Cambodge, Phnom Penh, Cambodia), Glenda Gray (Perinatal HIV Research Unit (PHRU), University of the Witwatersrand, Soweto, South Africa), Thérèse N'Dri-Yoman (Programme PAC-CI/ANRS, Abidjan, Côte d'Ivoire), Alpha Diallo (Department of Pharmacovigilance, Agence Nationale de Recherches sur le Sida et les hépatites virales (ANRS), Paris, France), Didier K. Ekouévi (Programme PAC-CI/ANRS, Abidjan, Côte d'Ivoire), François Dabis (INSERM U897, ISPED, Université Victor Segalen, Bordeaux, France).
Primary investigators: Professor François Dabis (INSERM U897, ISPED, Bordeaux, France) and Dr Didier Koumavi Ekouévi (PACCI ANRS, Abidjan, Côte d'Ivoire); coinvestigators: Professors Christine Rouzioux, Stéphane Blanche and Jean-Marc Treluyer, Dr Marie-Laure Chaix and Dr Elisabeth Rey (Paris, France), Professor N'Dri-Yoman (Abidjan, Côte d'Ivoire), Professor Kruy Leang Sim and Dr Eric Nerrienet (Phnom Penh, Cambodia) and Professors Glenda Gray and James McIntyre (Soweto, South Africa); Trial coordinator: Dr Elise Arrivé (Bordeaux, France).
Other members of the TEmAA ANRS 12109 Study Group (by place and alphabetic order):
Paris: Déborah Hirt, Saik Urien; Abidjan: Gérard Allou, Clarisse Amani-Bosse, Divine Avit, Gédéon Bédikou, Kouakou Brou, Patrick Coffié, Patrice Fian, Eulalie Kanga, Broulaye Kone, Suzanne Kouadio, Guy César Kouaho, Jeanne Eliam Kouakou, Sidonie Ngatchou, Touré Pety, Zenica Seoue, Mamourou Kone; Phnom Penh: Laurence Borand, Pinn Chou, Kearena Chhim, Meng Ly Ek, Viseth Horm Srey, Seng Hout, Sethikar Im, Saroeum Keo, Vannith Lim, Sopheak Ngin, Vara Ouk, Vibol Ung and the Magna and Maryknoll associations; Soweto: Gail Ashford, Promise Duma, Portia Duma, Sarita Lalsab, Shini Legote, Tshepiso Mabena, Joseph Makhura, Modise Maphutha, Selvan Naidoo, Mandisa Nyati.
Scientific Board: Professor Bernard Koffi Ngoran (Abidjan, Côte d'Ivoire), Professor Koum Kanal (Phnom Penh, Cambodia), Professor Lynn Morris (Johannesburg, South Africa), Dr Séverine Blesson (ANRS, Paris, France), Dr Camille Aubron-Olivier (Gilead Sciences, Paris, France), Professor Gilles Peytavin (Paris, France), Professor Koen Van Rompay (Davis, California, USA), Dr Valériane Leroy (Bordeaux, France); Independent Committee: Professor John Sullivan (Worcester, Massachusetts, USA); Philippe Lepage (Brussels, Belgium), Laurent Mandelbrot (Paris, France), Marie-Louise Newell (London, UK), Anne-Marie Taburet (Paris, France).
There are no conflicts of interest.
Reported in part at the 15th Conference on Retroviruses and Opportunistic Infections, Boston Massachusetts, USA, February 2008 (abstract S-141).
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