Epidemiology and Social
Field efficacy of zidovudine, lamivudine and single-dose nevirapine to prevent peripartum HIV transmission
ANRS 1201/1202 DITRAME PLUS Study Groupa,b,c,d,e,
From the aUnité INSERM 593, Institut de Santé Publique, Epidémiologie et Développement (ISPED), Université Victor Segalen, Bordeaux, France
bProgramme PACCI, Centre Hospitalier Universitaire (CHU) de Treichville, Abidjan
cCentre de Diagnostic et de Recherches sur le SIDA (CeDReS), CHU de Treichville, Abidjan
dCHU de Yopougon, Abidjan, Côte d’Ivoire
eLaboratoire de Virologie Médicale, CHU Necker Enfants Malades, Paris, France.
Received 12 July, 2004
Revised 3 December, 2004
Accepted 14 December, 2004
Correspondence to Pr François Dabis, INSERM U.593, ISPED, Université Victor Segalen, 146 Rue Léo Saignat, 33076 Bordeaux Cedex, France. E-mail: email@example.com
Objectives: In Africa, single-dose nevirapine (NVPsd), short regimens of zidovudine (ZDV) or ZDV + lamivudine (3TC) are recommended to prevent peripartum mother-to-child HIV transmission (PMTCT). We evaluated the 6-week field efficacy of two more PMTCT drug combinations.
Design: An open-label intervention cohort in Abidjan.
Methods: In 2001–2002, consenting women started oral ZDV 300 mg twice daily (bid) at ≥36 weeks of gestation, with 600 mg of ZDV + 200 mg NVPsd orally at beginning of labour. In 2002–2003, the antepartum regimen at ≥32 weeks comprised ZDV as previously + 3TC 150 mg bid; the labour dose comprised ZDV + NVPsd as previously + 300 mg 3TC orally. Neonates received ZDV syrup (2 mg/kg per 6 h) for 7 days + NVPsd syrup (2 mg/kg) on day 2 in both periods. Each woman was assisted to either use breast milk substitutes or breastfeed exclusively. Paediatric HIV infection was diagnosed by plasma HIV RNA viral load at 4 weeks, confirmed at 6 weeks. The reference group was a cohort receiving a short regimen of ZDV ≥ 36–38 weeks in 1995–2000 in the same population.
Results: A total of 1144 HIV-infected pregnant women were included: 351 with ZDV, 420 with ZDV + NVPsd and 373 with ZDV + 3TC + NVPsd; 1010 livebirths were eligible for analysis; 79 children were HIV-infected peripartum. Six-week transmission probability was 6.5% [95% confidence interval (CI), 3.9–9.1%) with ZDV + NVPsd, a 72% reduction compared with ZDV alone (95% CI, 52–88%; P = 0.0002 adjusted on maternal CD4, clinical stage and breastfeeding). It was 4.7% (95% CI, 2.4–7.0%) with ZDV + 3TC + NVPsd (P = 0.34 compared with ZDV + NVPsd).
Conclusions: A short-course of ZDV + NVPsd prevents most peripartum HIV transmission in Africa. This regimen could be added to international guidelines.
Mother-to-child transmission (MTCT) of HIV type 1 accounts for most of the 2000 newly acquired paediatric HIV infections in Africa each day . Several antiretroviral (ARV) regimens to prevent MTCT have been successfully evaluated and are recommended by the World Health Organization (WHO) since 2000 . Two ARV drugs are thus used in monotherapy: zidovudine (ZDV) and nevirapine (NVP).
ZDV given for the last four weeks of pregnancy plus the labour/delivery period has been evaluated in two placebo-controlled randomized trials in West Africa [3,4]. Transmission risk was 14.7% at 6 weeks in comparison with 24.8% with placebo, despite predominant breastfeeding exposure allowing for early HIV postnatal transmission . Open-label cohort studies confirmed the field efficacy or effectiveness of this ZDV regimen . The efficacy of maternal and neonatal NVP single dose (NVPsd) prophylaxis has been demonstrated first in a randomized, controlled trial in Uganda with a 6-week transmission rate of 11.8% . Another trial in South Africa demonstrated the statistical equivalence at 6 weeks of a NVP regimen, adding a second postpartum maternal NVP dose to the previous regimen, in comparison with a dual regimen of ZDV + lamivudine (3TC), 12 versus 9% .
Combinations of ARVs may further reduce MTCT in Africa as in Europe and in the USA . Although successfully evaluated in South Africa , in a multi-country African trial  and in France , the ZDV + 3TC combination may induce neonatal anaemia and viral resistance after ≥2 months of use and thus remains infrequently used.
We conducted a cohort study in Abidjan, Côte d’Ivoire to evaluate the acceptability, tolerance and effectiveness of: (1) a short-course peripartum ZDV regimen combined with NVPsd during labour (ZDV + NVPsd) and followed by a very short neonatal prophylaxis of ZDV + NVPsd; and (2) the same regimen with the addition of a maternal short-course of 3TC (ZDV + 3TC + NVPsd).
The ANRS 1201/1202 DITRAME PLUS project was conducted in two districts of Abidjan. HIV counselling and testing services were set up within the antenatal clinics of the Yopougon University Hospital and six community-run health facilities. Two sites served for enrolment and follow-up.
The study was an open-label intervention cohort. The study protocol was approved by the National Ethical Committee in Côte d’Ivoire and the French Agence Nationale de Recherches sur le SIDA (ANRS). The pooled data of two consecutive series of mother–infant pairs, receiving ZDV in the ANRS 049a trial in 1995–1998  or in a cohort on the same sites in 1999–2000 , were used for comparison. This regimen consisted of 300 mg ZDV tablets twice a day at ≥36 weeks of gestation, two tablets (600 mg) at beginning of labour and 1 week of maternal ZDV postnatally but no neonatal prophylaxis.
All pregnant women attending the selected clinics were offered pre-test counselling and HIV testing. Those ≥18 years old, at <32 weeks of gestation, living within the city limits and signing an informed consent were eligible. All serum samples were screened on site for HIV antibodies by an immunochromatographic rapid test (Determine®; Abbott Laboratories, Abbot Park, Illinois, USA). A negative diagnosis was based on this single test result. Positive samples were immediately confirmed on site by a second rapid test (Genie II®, Bio-Rad, Marnes-La-Coquette, France). Announcement of the seropositive status was made if both test results were positive. Women who tested positive with the two rapids tests or whose test results needed confirmation in the CeDReS reference laboratory  were systematically offered to enter the cohort if haemoglobinaemia was ≥7 g/decilitre (dl). Eligible women were scheduled for enrolment no later than at beginning of labour.
The drug combination regimen evaluated in 2001–2002 consisted of a daily antenatal oral regimen of 300 mg ZDV tablets twice a day at ≥36 weeks, two tablets (600 mg) of ZDV and a single NVP tablet (200 mg) at beginning of labour. The intrapartum package was given at inclusion. Intra-partum treatment was self-initiated by the woman as soon as the labour had started. A second intra-partum dose was given by the study team if women did not deliver within 48 h of administration of the first labour dose. In 2002–2003, the antenatal regimen was changed to ZDV 300 mg and 3TC 150 mg tablets twice a day at ≥32 weeks, followed by two tablets of ZDV (600 mg) and 3TC (300 mg) at beginning of labour plus NVPsd as previously. The ZDV + 3TC maternal regimen was continued for 3 days postpartum. The neonatal prophylaxis was the same in the two periods. At delivery the mother was given a container with ZDV syrup for her neonate with a mono-dose syringe, four times a day (2 mg/kg) for 7 days. Mothers were also asked to attend the study clinic 48–72 h after birth for directly observed administration of 2 mg/kg of NVPsd syrup to their neonate.
Women were advised at inclusion and during subsequent prenatal visits to either choose artificial feeding from birth  or exclusive breastfeeding with initiation of weaning as soon as possible after 4 months of life . Women were given support once their choice made, including free provision of equipment and supplies up to nine months postpartum .
Demographic, clinical information, maternal CD4 measured by flow cytometry and HIV-1 RNA plasma viral load were processed at entry in the study. Women were given weekly and then bi-weekly prepartum appointments for interview, clinical follow-up, drug distribution, verification of drug intake and tolerance. An appointment was given ≤48 h after delivery, then a week later at the end of the treatment period, and at weeks 4 and 6 postpartum. The clinical follow-up of the child followed the same schedule. Children's blood samples were obtained for diagnosis of HIV infection and haemoglobin measurement. Medical and psycho-social support was provided between scheduled visits. All prescribed medications, hospital stays and transportation were provided free of charge.
Diagnosis of paediatric HIV infection
Capillary blood was collected in EDTA microtainer tubes in new-borns at day 2; 1–2 ml of peripheral blood was taken at weeks 4 and 6. All samples collected at week 4 were processed for plasma RNA viral load measurement. The bDNA Versant HIV RNA kit version 3.0 (Bayer Diagnostics, Emeryville, California, USA) was applied to the ZDV cohort. A real-time polymerase chain reaction (PCR) (quantitative Taqman technology) was applied to cohorts with combination drug regimens. In comparison with the bDNA assay, the real-time PCR has shown 100% sensitivity and specificity (95% lower bounds of 93.7 and 98.3%, respectively) [16,17]. The same techniques were applied to the preceding available sample(s) and to the 6-week sample if the first one tested was positive. Both assays were controlled by the ANRS quality assurance programme. The diagnosis of paediatric HIV-1 infection was made on the basis of two positive virology tests . All samples with plasma HIV RNA > 5000 copies/ml were considered positive [16,17]. The first positive test in the series allowed the estimation of the timing of infection: in utero if the day 1–4 specimen was positive, intrapartum/early postpartum if the day 1–4 specimen was negative but the week 4–6 specimen was positive and timing of peripartum infection remained unknown in other instances . Absence of infection was defined by a negative test at the last time point an assay was done. Those children who had no sample available for testing and could not be followed >6 weeks were considered of definitive unknown HIV status.
Neonatal severe anaemia was defined by haemoglobinaemia <8 g/dl at week 4. All stillbirths, early neonatal (≤7 days) and neonatal (<28 days) deaths were taken into account. The frequency of maternal and neonatal clinical rash was estimated 7 days after delivery/birth.
The sample size of the ZDV + NVPsd cohort was calculated to estimate a 6-week MTCT risk of 7.5%, twice lower than with ZDV alone in a predominantly breast-feeding population , with a 5% type-I error (two-sided), a 10% type-II error and 10% of uninterpretable observations. This part of the study was terminated when its Scientific Committee after reviewing the available data concluded that the ZDV + NVPsd combination was superior to ZDV alone. The next regimen, ZDV + 3TC + NVPsd, was then evaluated. This part of the study was terminated when highly active antitretroviral combination therapy (HAART) became available on site for the prevention of MTCT. To guarantee statistical independence of observations, we selected the first livebirth when a woman gave multiple livebirths . Group comparisons used variance analysis, Student's t-test or non-parametric Mann–Whitney test for quantitative variables, and χ2 test or Fisher's exact test for qualitative variables. The 6-week probability of infection was estimated using the Kaplan–Meier survival technique considering age at infection as the mid-point between the last negative and the first positive test results . All factors potentially associated with MTCT were studied in univariate then bivariate analyses adjusted on treatment. Cox multivariate proportional hazards model was used to study the relative effectiveness of each treatment, expressed as one minus the hazard ratio (HR). Multivariate analyses of the effect of treatment used as adjustment variables those with P < 0.25 in bivariate analyses or P < 0.05 in the comparison of the treatment groups. The role of interaction terms was investigated. Point estimates of summary statistics are reported with their 95% confidence interval (95% CI).
Between September 1995 and July 2003, 1144 pregnant women were enrolled: 351 received ZDV alone, 420 ZDV + NVPsd and 373 ZDV + 3TC + NVPsd. There were 1120 maternal records available for analysis, of whom 56 women were lost to follow-up prior to delivery (Table 1). After exclusion of the multiple birth outcomes, the total number of births selected was 1064, including 22 stillbirths. Thirty-two eligible livebirths could not be taken into account in the analysis, either as there was no blood sample available (n = 17) or due to death in the first week of life (n = 15). The baseline and follow-up characteristics of the cohorts are summarized in Table 2. The proportion of women eligible for HAART according to the 2003 WHO criteria (clinical stage 4 or clinical stage 3 and CD4 cell count <350 × 106 cells/l or stage 1–2 and CD4 cell count <200 × 106 cells/l)  was 20.8%, including all the women (14.5%) with CD4 cell count <200 × 106 cells/l.
The median length of antenatal treatment was 21 days with ZDV, 29 with ZDV + NVPsd and 50 with ZDV + 3TC + NVPsd (Table 2). The proportion of women taking the ARV labour dose increased from 83% with ZDV alone to 93% with the two-drug combinations (P < 10–4). The postpartum ARV prophylaxis was generally taken. This component could not be compared between the groups as it differed (Table 2). There was no statistical difference between the three groups for place of delivery and frequency of Caesarian section, an infrequent practice (Table 2). The proportion of women who chose to breastfeed from birth was 54–66% in the two groups receiving ARV combinations, whereas it was 97.6% in the ZDV group (Table 2).
Maternal tolerance to the three drug regimens was good (Table 3), with a 0.5% incidence of severe anaemia in the first month postpartum. One woman, who was 32 years old, WHO clinical stage 1, CD4 cell count 228 × 106 cells/l and 8.1 g/dl haemoglobinaemia, initiated ZDV + 3TC at 32 weeks of gestation but stopped prophylaxis after 4 weeks with an hamoglobinaemia of 3.5 g/dl, corrected by a blood transfusion. Her child was infected in utero. There was no report of grade III or IV rash after the maternal NVPsd intake during labour. Severe neonatal anaemia was observed in 20 instances (2.2%), which was always transient. There was no report of grade III or IV rash after the neonatal NVPsd intake. The frequencies of perinatal deaths (stillbirths and early neonatal deaths) and low birthweight were comparable (P = 0.17 and 0.28, respectively, Tables 1 and 3). All neonatal deaths but two were recorded in the first week of life and their frequency was comparable between the three groups (P = 0.74; Table 3). All but one remained of indeterminate HIV status, without any relation with infant feeding modality.
There were 79 of 1010 neonates for whom the diagnosis of paediatric HIV infection was made (Table 1). For 29 of them, in utero transmission was considered. In 28 instances, transmission was classified as intrapartum or early postnatal, the 22 other infections remaining of unknown timing. The overall 6-week probability of transmission was 6.5% (95% CI, 3.9–9.1%) with ZDV + NVPsd and 4.7% (95% CI, 2.4–7.0%) with ZDV + 3TC + NVPsd (P = 0.34 after adjustment on maternal CD4 count, plasma HIV-1 RNA, WHO clinical stage, primigravida, duration of prepartum treatment, intrapartum treatment intake, low birthweight and breastfeeding). When using ZDV alone as reference (12.5% transmission at 6 weeks), the protective effect of the two-drug combinations was strong, with an adjusted effectiveness of 72% (95% CI, 45–86%) for ZDV + NVPsd and 76% (95% CI, 52–88%) for ZDV + 3TC + NVPsd (P < 0.0002 and 0.0001, respectively after adjustment for maternal CD4 cell count, WHO clinical stage, moderate anaemia, age, primigravida, low birthweight, duration of prepartum treatment, intrapartum treatment intake, Caesarian section and breastfeeding) (Table 4). There was neither an interaction between treatment and maternal CD4 cell count (P = 0.68) nor between treatment and infant feeding (P = 0.57). There was no statistical difference in the crude and adjusted risks of transmission at 6 weeks according to the infant feeding exposure. This adjustment factor never reached statistical significance in multivariate analyses (P = 0.10, Table 4). Thus, in comparison with ZDV alone, the relative effectiveness of the two drug combinations among the 703 breastfed children was 70% for ZDV + NVPsd (P < 0.002) and 77% for ZDV + 3TC + NVPsd (P < 0.003).
We stratified the sample according to the 2003 WHO criteria for HAART indication (P = 0.65 for the interaction of this variable with treatment). Among the 212 HAART-eligible women, the 6-week probability of peripartum infection was 23.6% with ZDV alone, 13.6% with ZDV + NVPsd and 9.1% with ZDV + 3TC + NVPsd (P = 0.28 and 0.10, respectively for the two comparisons using ZDV as reference). Among the 774 women who had no HAART indication, the 6-week peripartum transmission probability was 10.9% with ZDV alone, 3.6% with ZDV + NVPsd and 3.5% with ZDV + 3TC + NVPsd (P < 0.03 for both comparisons using ZDV as reference).
We could not investigate the relationship between the ARV regimens and the timing of acquisition of paediatric HIV infection as the majority of cases in the ZDV cohort were HIV RNA positive for the first time at ≥ day 7 (Table 1). Finally, the time period of enrolment was not investigated as the study of each drug regimen followed the previous one without any overlap. We verified however that the transmission rate did not vary by calendar year for each period of enrolment (data not shown).
We have demonstrated a high effectiveness for the ZDV + NVPsd regimen, which reduced peripartum MTCT by 72% compared with ZDV alone [3–6]. We cannot demonstrate an additional benefit of adding 3TC to ZDV + NVPsd although starting ZDV + 3TC a month earlier than ZDV. It is now internationally recognized that triple-drug combinations used together and not sequentially further reduce MTCT, especially for women who need HAART for themselves . However, we identified with ZDV + NVPsd a peripartum regimen that is particularly effective when HAART is not indicated, with comparable results to industrialized countries before the HAART era [9,21]. The 6-week residual risk was independent of the breastfeeding exposure. The prolonged duration of NVP levels in both the mother and the child over the first weeks of life may have reduced early transmission by breastmilk, an added benefit of NVPsd combined with ZDV or ZDV + 3TC. Two-year follow-up is under way to estimate the additional postnatal transmission risk and the cumulative effectiveness of our peripartum and postpartum packages .
Comparing the different ARV MTCT regimens directly is difficult. The first African placebo-controlled trials evaluated individual drug regimens [3,4,7,10]. Then, equivalence trials were designed . Three key parameters have varied from trial to trial and impair the direct comparison of published results. The median maternal CD4 cell count varied between 545 × 106 cells/l in West Africa ZDV studies  to 370 × 106 cells/l with ZDV + NVPsd (Table 2), 461 × 106 cells/l in the Uganda NVPsd trial  and 482 × 106 cells/l in the ZDV + 3TC trial . The frequency of Caesarian section was 30% in South Africa , 3–6% in our cohort and exceptionally elective. We introduced alternatives to prolonged and predominant breastfeeding whereas no neonatal intervention had been proposed in the ZDV reference cohort. Our estimate of the 6-week transmission risk includes early postnatal transmission, possibly partly controlled by the neonatal ZDV + NVPsd prophylaxis but impaired by other risk factors, low maternal CD4 cell count and low frequency of Caesarian section. These three factors were controlled for in all analyses. In doing so, our ZDV + NVPsd regimen had the lowest estimate of the residual transmission risk compared to ZDV alone [3,4], NVPsd , ZDV + 3TC, except its longest regimen with a residual transmission of 5.7% .
The DITRAME PLUS regimens were made of several components, each of them selected on the basis of previous evidence. We did not design the study to investigate their respective contribution as recently done in Thailand in a randomized trial . Indeed, their results strengthen our approach of adding NVPsd to a short-course ZDV regimen. This trial suggests also that the neonatal ZDV + NVPsd prophylaxis has an added value, with a 2.0% residual transmission versus 2.8% in the absence of neonatal NVPsd, although the difference remained below statistical significance . Neonatal NVPsd together with 1 week of ZDV has recently been shown to prevent more intrapartum transmission than NVPsd in Malawi when no ARV could be given before delivery/birth . This was not the case however when maternal NVPsd had been administered prior to delivery . Based on this evidence, the WHO recommends as first-line regimen the combination of a short course of ZDV for pregnant women at ≥28 weeks and children, for at least 1 week, with NVPsd for both .
We chose a non-randomized approach to estimate the treatment effect as we considered there was a priori lack of equipoise between ZDV + NVPsd and ZDV alone. Indeed, ethical principles and time constraints can legitimize the use of non-randomized designs . The Thai trial conducted at the same time as our study stopped its ZDV alone arm after its first interim analysis as it was already inferior to the two arms evaluating ZDV + NVPsd combinations . We acknowledge that beyond the important confounding factors systematically controlled for, such as the clinical and immunological stage of HIV disease, the breastfeeding exposure and the duration of the ARV prophylaxis, unconsidered factors could not be taken into account by our design. Of note, the uptake in the cohorts remained constant over time .
Viral resistance has not been a concern with short-course ZDV . In the Uganda NVPsd trial, the resistance mutations were transiently diagnosed in 19% of the mothers but were not associated with transmission [28,29]. The acquisition of different patterns of transient resistance by 46% of the infected children in this trial was considered due to the neonatal NVPsd rather than to the transmission of resistant virus . Using NVPsd in combination with other drugs, the incidence of viral mutations at 6-week postpartum was 15% in industrialized countries . Early results of resistance studies within our cohort confirm that NVP resistance occurs at a high frequency among mothers (33%) and children (23%) despite the use of ZDV + NVPsd instead of NVPsd . Further studies will determine whether resistance to 3TC has been added to resistance to NVPsd [11,32] and conversely, if the 3-day maternal postpartum ZDV + 3TC regimen has influenced the occurrence of maternal NVP resistance  or not. The consequences of viral resistance after NVPsd exposure on the subsequent response to HAART in women and children should be urgently investigated in Africa as in the Thai trial  considering the possible large-scale adverse effect on subsequent treatment options.
The ZDV + 3TC + NVPsd regimen we evaluated was selected at a time when access to HAART was too limited in Côte d’Ivoire to be considered during pregnancy. Our choice was based on the demonstrated efficacy of short-courses of ZDV + 3TC in the ANRS 075 cohort in France  and in the PETRA trial in Africa . We did not demonstrate an enhanced effectiveness of this regimen in comparison with ZDV + NVPsd, although our study had limited statistical power, an uneven distribution of confounding variables between the two groups (controlled for in the analysis) and was terminated mid-2003 as soon as HAART became available on site.
The ZDV + NVPsd MTCT prophylactic regimen we evaluated is now part of the list of internationally recommended drug regimens by WHO . Once the benefit (effectiveness)/risk (resistance) ratio of the ZDV + 3TC + NVPsd combination is known, this regimen may also be considered. Four areas now require further research consideration. First, the uptake of ARV peripartum interventions is critical to obtain a public health impact. ZDV and NVPsd are not easy to use in Africa [35–37]. Their combined use will not be necessarily more complex but the challenge is to improve coverage . Second, the reduction of the risk of postnatal transmission should be addressed, either with infant feeding strategies  or with ARV-based approaches . Third, alternatives to NVPsd-containing regimens should be investigated as viral resistance and impaired response to subsequent ARV treatment is a serious concern. Finally, the residual transmission we observed with ZDV + NVPsd cannot be considered fully satisfactory. HAART is now universally recommended for pregnant women who fulfil this indication for themselves . We demonstrate in a large African cohort, as in a randomized trial in Thailand, that a short-course peripartum ZDV regimen combined with NVPsd is more effective than previously used single drug regimens and will greatly contribute to the prevention of paediatric HIV infection if rapidly and widely used.
François Dabis was the director and co-primary investigator of the entire project, supervized the epidemiological aspects of the study and wrote the manuscript. Laurence Bequet was the study co-ordinator of all aspects of the project on site. Didier Koumavi Ekouevi was the chief data manager and participated in the data analysis and manuscript writing. Ida Viho was the clinical director and monitored the entire study. François Rouet was responsible for all laboratory aspects of the project on site and contributed to the writing of the manuscript. Charlotte Sakarovitch and Laurence Dequae-Merchadou prepared and conducted data analysis. Apollinaire Horo clinically supervized the antenatal and obstetric phases of the study. Renaud Becquet contributed to data monitoring and was particularly in charge of surveillance of adverse events. Patricia Fassinou supervized the paediatric phase of the project clinically. Christiane Welffens-Ekra was the obstetrician primary investigator of the project. Christine Rouzioux supervized the laboratory component of the project and ensured quality control. Valériane Leroy was the co-primary investigator of the project, was responsible for evaluation of postpartum interventions and participated in the manuscript writing.
The primary sponsor of the DITRAME PLUS project was the French Agence Nationale de Recherches sur le Sida (ANRS), France. Laurence Bequet and François Rouet were supported by the French Ministry of Foreign Affairs. Didier K. Ekouevi was a fellow of the French Charity Ensemble contre le Sida. Renaud Becquet was a fellow of the French Ministry of Education, Research and Technology. The authors wish to acknowledge the support of the Developing Country Unit of the ANRS, particularly Drs Brigitte Bazin and Séverine Blesson, and Mrs Chantal Canon and Névada Mendes. Zidovudine and lamivudine were provided by Glaxo Smith Kline International. Dr Guillaume Walckenaer and Mrs Cecile Thiaux (Glaxo Smith Kline France) facilitated the zidovudine and lamivudine drug supply throughout the study. Pr Marie-Claude Saux, Mrs Dominique Breilh and Mr Bruno Fallour (Pharmacie Centrale, Hôpital du Haut-Lévêque, Pessac, France) were in charge of drug packaging. Euclidis (Pessac, France) ensured quality control of the study drug preparation and was responsible for shipment from France to Côte d’Ivoire. The Board of the Formations Sanitaires Urbaines Communautaires participating as study sites actively supported the project. Special thanks to Marie-Pierre Martin, Isabelle Bely, Bertin Kouadio and Philippe Lepère for the administrative management of the study. Finally, we would like to thank Drs Philippe Msellati and Nicolas Meda for their contribution to the ANRS 049 DITRAME reference study and the women and children who agreed to participate to the DITRAME PLUS project.
Note. This study was presented in part at the 14th International AIDS Conference, 7–12 July 2002 (Barcelona, Spain), [abstract ThOrD1428], the 10th Conference on Retroviruses and Opportunistic Infections, Boston, MA (USA), 10–14 February 2003, [abstract 854] and the Second IAS Conference on HIV Pathogenesis and Treatment, Paris (France), 13–17 July 2003, [abstract 219].
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Composition of the ANRS 1201/1202 DITRAME PLUS Study Group
Writing committee: François Dabis, Laurence Bequet, Didier Koumavi Ekouevi, Ida Viho, François Rouet, Apollinaire Horo, Charlotte Sakarovitch, Renaud Becquet, Patricia Fassinou, Laurence Dequae-Merchadou, Christiane Welffens-Ekra, Christine Rouzioux, Valériane Leroy.
Principal investigators: François Dabis, Valériane Leroy, Marguerite Timite-Konan, Christiane Welffens-Ekra.
Coordination in Abidjan: Laurence Bequet, Didier Koumavi Ekouévi, Besigin Tonwe-Gold, Ida Viho.
Clinical team: Clarisse Amani-Bosse, Ignace Ayekoe, Gédéon Bédikou, Nacoumba Coulibaly, Christine Danel, Patricia Fassinou, Apollinaire Horo, Ruffin Likikouet, Hassan Toure.
Laboratory team: Dominique Bonard, André Inwoley, Crépin Montcho, François Rouet, Ramata Touré.
Biostatistics and data management: Gérard Allou, Renaud Becquet, Katia Castetbon, Laurence Dequae-Merchadou, Charlotte Sakarovitch, Dominique Touchard.
Psycho-social team: Hortense Aka-Dago, Herman Brou, Annabel Desgrées du Loû, Alphonse Sihé, Benjamin Zanou.
Scientific committee: Stéphane Blanche, Jean-François Delfraissy, Philippe Lepage, Laurent Mandelbrot, Christine Rouzioux, Roger Salamon.
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Africa; HIV infections; vertical transmission; prevention; lamivudine; nevirapine; zidovudine
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