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Background: Large numbers of women receive single-dose nevirapine (sdNVP) to prevent mother-to-child transmission (MTCT) of HIV; over time, an increasing proportion will return to prevention of MTCT programs for a second pregnancy. Because sdNVP selects resistance in a high percentage of women, we compared the effectiveness of sdNVP in preventing peripartum MTCT in successive pregnancies. Methods: Prospective cohorts were recruited from MTCT programs in South Africa and Cote d'Ivoire. HIV-1-infected women and their infants exposed to sdNVP in 2 consecutive pregnancies-used alone or with zidovudine (ZDV) or ZDV plus lamivudine-were included. Results: The median age of women at their initial exposure to sdNVP in Soweto (n = 120) and Abidjan (n = 41) was 26 (interquartile range [IQR]: 22-29) years and 28 (IQR: 24-31) years, respectively, and their median delivery interval was 21 (IQR: 15-29) months and 26 (IQR: 20-32) months, respectively. Transmission rates in Soweto and in Abidjan were 11.1% and 13.2% for the first pregnancy and 11.1% and 5.4% for the second pregnancy (P = 1.000 and P = 0.449 for Soweto and Abidjan, respectively, in unpaired analysis). Conclusion: This analysis suggests that the effectiveness of sdNVP when used in successive pregnancies is probably not impaired, possibly because viral resistance selected by prior exposure to sdNVP may wane with time.

Nonnucleoside reverse transcriptase inhibitor resistance following the use of single-dose nevirapine (sdNVP) for the prevention of mother-to-child transmission (PMTCT) remains a concern. In the ANRS-1201/1202 Ditrame study, conducted in Abidjan, Côte d'Ivoire, a short-course regimen of zidovudine was associated with sdNVP for PMTCT. In this study, we estimate the frequency of NVP resistance and its relationship with NVP concentration in mothers. Genotypic resistance analysis was performed on mothers' plasma samples at week 4 postpartum (PP) and on human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells (PBMC) when an NVP resistance mutation was detected. The same tests were performed for the infected children at week 4, month 3, and month 12. Mothers' NVP plasma concentrations were measured at 48 h PP. Twenty-one (33%) of the 63 women selected had NVP-resistant (NVP-R) virus at week 4 PP. The median plasma NVP concentration was 598 ng/ml for the mothers without NVP-R virus compared to 851 ng/ml for the mothers harboring NVP-R virus ( P = 0.014). NVP-R mutations were detected in the HIV DNA of 15/20 women. Plasma NVP-R mutations were detectable in 6 of 26 infected children at week 4. All 6 children had detectable NVP-R mutations in HIV DNA of PBMC. Blood samples taken at month 3 (1 child) and month 12 (1 child) revealed the persistence of NVP-R mutations in plasma and cells. Emergence of NVP-R virus in mothers is strongly correlated with a high level of plasma NVP concentration, owing to a prolonged postpartum period of viral replication under NVP selective pressure. The follow-up of the cohort demonstrates the prolonged archive of resistant virus.

BACKGROUND. Mitochondrial toxicity was described in infants exposed to long-term antiretroviral regimens containing nucleoside analogues for the prevention of mother-to-child transmission of HIV. We measured the serum lactate levels in children born to HIV-1 infected African women receiving short-term antiretroviral prevention of mother-to-child transmission of HIV regimens. METHODS. A prospective study was conducted in women-child pairs from the third trimester of pregnancy to 3 months of life. The exposed group was formed by children exposed in utero to nucleoside analog antiretroviral regimens, zidovudine or zidovudine + lamivudine from 32 to 36 weeks of amenorrhea until delivery. All of these women received nevirapine single dose at the beginning of labor. The children received zidovudine during the first 7 days of life and a nevirapine single dose at day 3. The control group was formed by infants born to HIV-1-infected women who had received nevirapine single dose only and who were not exposed to nucleoside analog antiretroviral regimens. Serum lactate levels were measured at 4, 6, and 12 weeks of life by Cobas Integra 400. RESULTS. A total of 836 blood samples from 338 infants was collected (262 exposed and 76 controls). Median lactacidemia was 1.8 mmol/L (interquartile range: 1.2–2.7 mmol/L). Overall serum lactate levels ≥2.5 mmol/L, defining hyperlactatemia, were observed in 39 of the 292 infants who had ≥2 serum lactate measurements. The 3-month period prevalence of hyperlactatemia did not differ between the exposed group and the control group. All of the serum lactate levels returned to normal values in all of the subsequent samples. No case of symptomatic hyperlactatemia was detected during the study period. CONCLUSIONS. Increased lactate levels were identified equally in infants whose mother received short-term nucleoside analogs or nevirapine single dose for prevention of mother-to-child transmission of HIV. Although not rare, hyperlactatemia was not related to short-term exposure to nucleoside analog antiretroviral regimens.

The frequency of resistance mutations was estimated in the cohort of Agence Nationale de Recherches sur le SIDA Ditrame Plus, a study that evaluated the combination of short-course zidovudine (ZDV) plus lamivudine (3TC) and single-dose nevirapine (SD-NVP) followed by 3 days of postpartum ZDV plus 3TC for the prevention of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1). The frequency with which resistance mutations were detected in mothers at week 4 postpartum was 1.14% (95% confidence interval [CI], 0.03%-6.17%) for NVP and 8.33% (95% CI, 3.66%-15.76%) for 3TC. In multivariate analysis, 3TC resistance was associated with a longer duration of ZDV plus 3TC prepartum prophylaxis (P=.009). This regimen, which is feasible in resource-limited settings, prevents most peripartum HIV-1 transmission and minimizes the development of NVP resistance.

Antenatal HIV seroprevalence surveys are important tools to understand the extent of the HIV epidemic in Africa. The main objective is to describe HIV prevalence trends from 1995–2002 in pregnant women consulting antenatal clinics in Abidjan, Côte d'Ivoire. We proposed HIV test to pregnant women consulting antenatal clinics in Abidjan from 1995–2002 in a programme of prevention of mother-to-child transmission of HIV. Yearly prevalence was estimated. Overall, 36,442 women were tested. Prevalence decreased from 14–15% in 1995–96 to 11% in 2002. The prevalence among 18–22-year-old women dropped from 15% in 1995 to 8% in 2002, while for older women it increased slightly, or remained stable from 1995–1999 and decreased thereafter. HIV prevalence among women consulting antenatal clinics has been decreasing overall. This is the first such report among pregnant women in Abidjan, probably the result of different phenomena: ageing of the epidemic and behaviour changes (disease awareness and prevention campaigns).

The Ditrame Plus project conducted in Abidjan, Côte d’Ivoire is aimed at the prevention of mother-to-child transmission of HIV in combining perinatal antiretroviral interventions with a systematic proposal of alternatives to prolonged breastfeeding: formula-feeding from birth, or exclusive breastfeeding during three months then early cessation of breastfeeding. We surveyed all health care workers involved in this project in November 2003 using a self-administered anonymous questionnaire to investigate their knowledge, attitudes and beliefs regarding the infant feeding interventions proposed since March 2001. Their knowledge regarding infant practices proposed within the study was consistent and their attitude was in accordance with the study protocol. However, proposing alternatives to prolonged breastfeeding induces difficulties to health-care workers that should be taken into account when tailoring such complex interventions.

The aim of this study was to describe baseline infant feeding practices in women of unknown HIV status in Abidjan, Côte d'Ivoire, before the implementation of infant feeding interventions aimed at the prevention of mother-to-child transmission of HIV through breastmilk. We conducted a cross-sectional survey in March 2000 among 225 mothers attending community-run health facilities with their own child for either immunization or weighting. All but two children had ever been breastfed, of whom 94 per cent were still being breastfed at 6 months of age. Exclusive breastfeeding was not practiced in this population since all women had given water to their child, starting in median one day after birth. Moreover, 20 per cent of the mothers had introduced infant formula in median three weeks after delivery. This study provides useful information for planning purposes in this urban African population, where exclusive breastfeeding is rare and the use of infant formula relatively common.

A retrospective survey estimating the prevalence of hepatitis viruses B (HBV) and C (HCV) was conducted on samples taken in 1,002 African pregnant women (501 diagnosed as HIV-1 positive and 501 HIV-1 negative) participating in a clinical trial program conducted in Abidjan, Cote d'Ivoire (West Africa). Hepatitis B markers studied were HBs antigen (HBsAg), and if positive, HBe antigen/anti-HBe antibodies and HBV DNA. Two third generation (G3) HCV enzyme immunoassays (EIAs) were used for primary HCV screening. All anti-HCV antibody-positive sera were assessed further with supplementary assays (one another G3 EIA, RIBA 3.0, and HCV RNA). HCV genotypes were also determined. HBsAg was found in a similar proportion among HIV-positive (45/499, 9.0%, 95% confidence interval [95% CI], 6.6-11.9) and HIV-negative (40/498, 8.0%, 95% CI, 5.8-10.8) women (P = 0.58). The diagnosis of chronic hepatitis B, based on HBV DNA positive results, was more frequent in HIV-positive women (26.7%), compared to HIV-negative women (9.4%) (P = 0.06). In the case of hepatitis C infection, after supplementary testing allowing the elimination of frequent false-positive screening results, a prevalence rate of about 1% was found, both in HIV-positive (6/501, 1.2%, 95% CI, 0.44-2.59) and HIV-negative (4/501, 0.8%, 95% CI, 0.22-2.03) women (P = 0.53). Of the 10 samples confirmed positive and assessed for HCV RNA, eight (80%) were viraemic and belonged to HCV genotypes 1 or 2. The relative high frequency of HIV/HBV coinfection in Cote d'Ivoire emphasises the need for monitoring the risk of hepatotoxicity by antiretroviral therapy in such patients. We propose an accurate and cost-efficient algorithm for HCV diagnosis in Africa.

A study was conducted in 1999-2000 in Abidjan within the ANRS 049 Ditrame project to describe the adherence of African HIV-infected women to counseling on protected sexual intercourse and contraceptive use after the announcement of their HIV test result during pregnancy. The incidence of pregnancy was 16.5/100 women-years at risk during the first 24 months postpartum. The factor most influencing the decision to start a new pregnancy was a high level of education which tripled this risk. (authors)

The objective was to evaluate the performance of a quantitative plasma HIV-1 ribonucleic acid (RNA) assay for HIV infection diagnosis among African breastfed children. Serial plasma specimens collected in the first week at day 45-90 6 months and 9-12 months of age from HIV-exposed children born to HIV-1 infected women enrolled in the DITRAME ANRS 049a perinatal intervention trial (Abidjan Cote dIvoire) were tested for HIV-1 plasma RNA using a branched deoxyribonucleic acid (bDNA) assay. Sensitivity and specificity of this RNA test were assessed in comparison with a qualitative DNA polymerase chain reaction (PCR) performed on the same blood samples and allowing a reliable detection of the predominant subtype A. Among 91 samples from 53 infected children which tested positive by DNA PCR the sensitivity of the bDNA test was 100% [95% confidence interval (CI) 96.0-100.0] at

To describe the haematological profile of pregnant women and to compare these characteristics according to HIV serostatus in Abidjan, Cote d'Ivoire, a cross-sectional study was made in the context of a research intervention programme to reduce mother-to-child transmission (MTCT) of HIV (ANRS 049 trial). HIV testing was systematically proposed to pregnant women attending the mother and child health clinic of a community health centre. Blood samples were tested for HIV antibodies using Genelavia™ and Peptilav™. The haematological parameters were measured with a Coulter counter. From May 1995 to March 1996, 1646 pregnant women accepted HIV testing and had a full blood count available. The prevalence of HIV infection was 12·0% (n = 197). The prevalence of anaemia (haemoglobin [Hb]

Desgrées du Lou Annabel, Msellati P., Viho I., Welffens-Ekra C- The use of induced abortion in Abidjan: a possible cause of the fertility decline? Fertility in Côte d'Ivoire has declined rapidly over the last 15 years, with the average number of children per woman falling from 7.2 in 1980 to 5.7 in 1994, despite the fact that contraceptive use remains very low. Of the different possible mechanisms for birth spacing, induced abortion in this country, where it is illegal and often performed clandestinely, remains poorly understood. In this study the pregnancy histories of 1201 women in the city of Abidjan are examined to determine the level and change in the use of abortion. This suggests that there is now a frequent use of induced abortion in Côte d'Ivoire (one third of women have aborted at least once) and that this has recently increased. The generalization of abortion seems to have occurred in the last ten years; all age groups are involved but especially the youngest, who begin to use abortion from the start of their fertile life, in contrast to older women who use it rather as a means of birth spacing and birth control after the first pregnancies. This rapid increase in the use of abortion is one of the explanatory factors for the fall in fertility in Côte d'Ivoire., Desgrées du Loû Annabel, Msellati P., Viho I., Welffens-Ekra C.-Le recours à l'avor- tement provoqué à Abidjan : une cause de la baisse de la fécondité ? En Côte d'Ivoire, la fécondité a baissé rapidement au cours des quinze dernières années : le nombre moyen d'enfants par femme est passé de 7,2 en 1980 à 5,7 en 1994, et ceci malgré une prévalence contraceptive encore très faible. Parmi les différents moyens d'espacement des naissances possibles, il en est un qui reste très mal connu dans ce pays, car illégal et souvent clandestin : le recours à l'avortement provoqué. Cette étude présente les niveaux de recours à l'avortement et leur évolution, à partir des vies génésiques de 1201 femmes enceintes dans la ville d'Abidjan. Il semble qu'il y ait actuellement en Côte d'Ivoire un recours à l'avortement provoqué fréquent (un tiers des femmes ont avorté au moins une fois), et que ce phénomène se soit récemment amplifié. La généralisation du recours à l'avortement se serait faite au cours des dix dernières années ; elle a touché toutes les classes d'âge, mais plus particulièrement les plus jeunes qui commencent à utiliser l'avortement dès le début de leur vie féconde, au contraire de leurs aînées qui l'utilisaient plutôt comme un moyen d'espacement et de limitation des naissances après les premières grossesses. Cette augmentation rapide du recours à l'avortement explique en partie la baisse de fécondité de la Côte d'Ivoire., Desgrées du Loú Annabel, Msellati P., Viho I., Welffens-Ekra C.-El recurso al aborto provocado en Abidjan, Desgrées Du Lou Annabel, Msellati P., Viho I., Welffens-Ekra C. Le recours à l'avortement provoqué à Abidjan : une cause de la baisse de la fécondité?. In: Population, 54ᵉ année, n°3, 1999. pp. 427-446.

The aim of this paper is to determine the differences of fertility between HIV 1 infected and uninfected women in Abidjan, Cote d Ivoire, using data available in an observational study conducted in 1995 and 1996 in 2 antenatal care centres in the district of Yopougon, Abidjan, within an intervention programme to reduce mother to child HIV 1 transmission DITRAME project, ANRS 049 . Fertility indicators have been constructed from retrospective data on pregnancies and births, and univariate and multivariate analyses have been performed on these indicators and stratified by age groups to compare HIV 1 positive and HIV negative populations. The main outcome measures were the number of pregnancies, the number of miscarriages, the risk of miscarriage and the proportion of primigravida. Four thousand, three hundred and ninety six women agreed to HIV testing: 12.1 were found to be HIV 1 infected. HIV 1 positive women had significantly fewer pregnancies than HIV negatives in age groups 25-29 P =0.05 and 30-34 P =0.008 . The risk of having had at least one abortion or stillbirth was significantly higher for HIV 1 infected women than for HIV negatives OR=1.28, 95 CI: 1.02-1.60 , when controlling for social and demographic factors. This study suggests that HIV 1 infection has deleterious consequences on female fertility, with lower fertility rates and more frequent adverse pregnancy outcomes. Family planning and antenatal care services should consider antenatal HIV counselling and testing in women in areas of high HIV prevalence.

OBJECTIVE: Our aim was to study the response to antiretroviral treatment among women exposed to single-dose nevirapine (NVP) and/or short-course zidovudine (ZDV; with or without lamivudine [3TC]) for the prevention of mother-to-child transmission of human immunodeficiency virus (HIV) infection. METHODS: All HIV type 1-infected women who initiated antiretroviral treatment with stavudine or ZDV, 3TC, and NVP or efavirenz were eligible for the MTCT-Plus program in Abidjan, Ivory Coast. Exposed women had received either single-dose NVP alone or short-course ZDV (with or without 3TC) plus single-dose NVP during previous pregnancy. Genotypic resistance testing was performed at week 4 after delivery. Virologic failure was defined as a plasma HIV RNA level >500 copies/mL 12 months after initiation of antiretroviral treatment. RESULTS: Among 247 women who received antiretroviral treatment, 109 (44%) were unexposed; 81 had received short-course ZDV with 3TC, as well as single-dose NVP; 5 had received short-course ZDV plus 3TC; 50 had received short-course ZDV plus single-dose NVP; and 2 had received single-dose NVP alone. No ZDV mutation was detected in the 115 women whose specimens were available for genotypic testing; 11 (15.1%) of 73 women with 3TC exposure who were tested after delivery had 3TC resistance mutations. Three (4.3%) of 69 women exposed to short-course ZDV and 3TC plus single-dose NVP and 16 (38.1%) of 42 women exposed to short-course ZDV plus single-dose NVP had NVP resistance mutations. Antiretroviral treatment was initiated a median of 21 months after the intervention to prevent mother-to-child HIV transmission (median CD4(+) T lymphocyte count, 188 cells/mm(3)). Month 12 virologic failure was identified in 42 (19.2%) of 219 women for whom data were available, and multivariate analysis revealed that it was associated with poor adherence to treatment (adjusted odds ratio [aOR], 12.7; 95% confidence interval [CI], 3.0-53.9), postpartum 3TC resistance mutations (aOR, 6.9; 95% CI, 1.1-42.9), and a baseline CD4(+) T lymphocyte count

International audience; OBJECTIVE: To evaluate the risk of postnatal HIV transmission among women in Abidjan, Côte d'Ivoire offered alternatives to prolonged breastfeeding, and to assess the impact of the breastfeeding pattern and duration on this risk. METHODS: In 2001-2003, HIV-infected pregnant women received peri-partum antiretroviral prophylaxis and were counselled antenatally regarding infant feeding options: formula feeding or exclusive breastfeeding with early cessation from 4 months of age. The primary outcome was HIV postnatal transmission by 18 months of age, defined by a positive HIV test after a negative test > or =30 days. The effect of the pattern (mixed feeding, defined as breastmilk plus food-based fluid, solid food or non-human milk) and duration (less vs. more than 6 months) of breastfeeding on postnatal transmission was assessed. RESULTS: Of 622 live-born infants who were HIV uninfected at or after 30 days, 15 were infected postnatally, 13/324 among breastfed, and 2/298 among formula-fed infants. The 18-month probability of remaining free from HIV infection was 0.95 [95% CI, 0.92-0.97] and 0.99 [95% CI, 0.97-1.00] in the breastfeeding and formula-feeding groups respectively (p

International audience; We studied whether the use of T-lymphocyte CD4 (CD4) absolute count instead of CD4 percentage could affect the decision process regarding HAART initiation in African HIV-infected pregnant women. A prospective cohort in Abidjan, C?d'Ivoire before HAART was available. Participating women received a perinatal antiretroviral prophylaxis (zidovudine + single-dose of nevirapine). CD4 count and percentage were measured by flow cytometry at baseline (32 weeks of amenorrhea) and at 1 month after delivery. A signed-rank test was used to compare the distributions of the CD4 absolute count and percentage values. A total of 325 HIV-1-infected pregnant women were included. At baseline, their median CD4 count was 355 cells/mm(3) and the median CD4 percentage was 24.8%; 17.8% of women had a CD4 count

BACKGROUND: In Africa, women tested for HIV during antenatal care are counselled to share with their partner their HIV test result and to encourage partners to undertake HIV testing. We investigate, among women tested for HIV within a prevention of mother-to-child transmission of HIV (PMTCT) programme, the key moments for disclosure of their own HIV status to their partner and the impact on partner HIV testing. METHODS AND FINDINGS: Within the Ditrame Plus PMTCT project in Abidjan, 546 HIV-positive and 393 HIV-negative women were tested during pregnancy and followed-up for two years after delivery. Circumstances, frequency, and determinants of disclosure to the male partner were estimated according to HIV status. The determinants of partner HIV testing were identified according to women's HIV status. During the two-year follow-up, disclosure to the partner was reported by 96.7% of the HIV-negative women, compared to 46.2% of HIV-positive women (chi(2) = 265.2, degrees of freedom [df] = 1, p < 0.001). Among HIV-infected women, privileged circumstances for disclosure were just before delivery, during early weaning (at 4 mo to prevent HIV postnatal transmission), or upon resumption of sexual activity. Formula feeding by HIV-infected women increased the probability of disclosure (adjusted odds ratio 1.54, 95% confidence interval 1.04-2.27, Wald test = 4.649, df = 1, p = 0.031), whereas household factors such as having a co-spouse or living with family reduced the probability of disclosure. The proportion of male partners tested for HIV was 23.1% among HIV-positive women and 14.8% among HIV-negative women (chi(2) = 10.04, df = 1, p = 0.002). Partners of HIV-positive women who were informed of their wife's HIV status were more likely to undertake HIV testing than those not informed (37.7% versus 10.5%, chi(2) = 56.36, df = 1, p < 0.001). CONCLUSIONS: In PMTCT programmes, specific psychosocial counselling and support should be provided to women during the key moments of disclosure of HIV status to their partners (end of pregnancy, weaning, and resumption of sexual activity). This support could contribute to improving women's adherence to the advice given to prevent postnatal and sexual HIV transmission.

International audience; BACKGROUND: Little is known about the long-term safety of infant feeding interventions aimed at reducing breast milk HIV transmission in Africa. METHODS AND FINDINGS: In 2001-2005, HIV-infected pregnant women having received in Abidjan, C?d'Ivoire, a peripartum antiretroviral prophylaxis were presented antenatally with infant feeding interventions: either artificial feeding, or exclusive breast-feeding and then early cessation from 4 mo of age. Nutritional counseling and clinical management were provided for 2 y. Breast-milk substitutes were provided for free. The primary outcome was the occurrence of adverse health outcomes in children, defined as validated morbid events (diarrhea, acute respiratory infections, or malnutrition) or severe events (hospitalization or death). Hazards ratios to compare formula-fed versus short-term breast-fed (reference) children were adjusted for confounders (baseline covariates and pediatric HIV status as a time-dependant covariate). The 18-mo mortality rates were also compared to those observed in the Ditrame historical trial, which was conducted at the same sites in 1995-1998, and in which long-term breast-feeding was practiced in the absence of any specific infant feeding intervention. Of the 557 live-born children, 262 (47%) were breast-fed for a median of 4 mo, whereas 295 were formula-fed. Over the 2-y follow-up period, 37% of the formula-fed and 34% of the short-term breast-fed children remained free from any adverse health outcome (adjusted hazard ratio [HR]: 1.10; 95% confidence interval [CI], 0.87-1.38; p = 0.43). The 2-y probability of presenting with a severe event was the same among formula-fed (14%) and short-term breast-fed children (15%) (adjusted HR, 1.19; 95% CI, 0.75-1.91; p = 0.44). An overall 18-mo probability of survival of 96% was observed among both HIV-uninfected short-term and formula-fed children, which was similar to the 95% probability observed in the long-term breast-fed ones of the Ditrame trial. CONCLUSIONS: The 2-y rates of adverse health outcomes were similar among short-term breast-fed and formula-fed children. Mortality rates did not differ significantly between these two groups and, after adjustment for pediatric HIV status, were similar to those observed among long-term breast-fed children. Given appropriate nutritional counseling and care, access to clean water, and a supply of breast-milk substitutes, these alternatives to prolonged breast-feeding can be safe interventions to prevent mother-to-child transmission of HIV in urban African settings.

Prenatal HIV counselling and testing is mainly an entry-point to the prevention of mother-to-child transmission of HIV, but it may also play an important role in triggering the development of spousal communication about HIV and sexual risks and thus the adoption of a preventive attitude. In Abidjan, Cote d’Ivoire, we investigated couple communication on STIs and HIV, male partner HIV-testing and condom use at sex resumption after delivery among three groups of pregnant women who were offered prenatal counselling and HIV testing: HIV-infected women, uninfected women, and women who refused HIV-testing. The proportion of women who discussed STIs with their regular partner greatly increased after prenatal HIV counselling and testing in all three groups, irrespective of the women’s serostatus and even in the case of test refusal. Spousal communication was related to more frequent male partner HIV-testing and condom use. Prenatal HIV counselling and testing proposal appears to be an efficient tool to sensitize women and their partner to safer sexual practices.

The early diagnosis of pediatric HIV-1 infection is a critical issue in resource-limited settings to prioritize eligibility for antiretroviral therapy among HIV-1-infected children. A case-control study was performed within the ANRS 1201/1202 Ditrame Plus cohort (Abidjan Cote dIvoire) to assess the usefulness of CD4+ T-cell percentage (CD4%) and total lymphocyte count (TLC) measured early in life in African children born to HIV-1-infected mothers. Using plasma HIV-1 RNA testing at 4 weeks of life as gold standard CD4% and TLC were determined at month 3 and 6 in all 33 children HIV-1-infected in utero or intrapartum/early postpartum (cases) born to mothers receiving peripartum antiretroviral prophylaxis. Controls were 66 HIV-1-uninfected children from the same cohort. At month 3 the median CD4% was significantly lower in HIV-1-infected children (17.7% 95% percentiles 7.1--27.4) than in uninfected controls (34.8% 18.5--45.3) (P < 0.001). A comparable difference was also observed at month 6. At the same time points no significant difference was measurable for TLCs. The best threshold differentiating HIV-infected and uninfected children at month 3 was 25% CD4+. Compared to HIV-1 RNA results sensitivity of this marker was 87.1% (95% confidence interval 70.2--96.4) at month 3 and 88.9% (70.8--97.6) at month 6. Specificity was 78.3% (63.6--89.0) and 88.3% (77.4--95.2) respectively. Early CD4% measurement allows one to classify adequately the vast majority of exposed children according to their HIV status. CD4% should be further evaluated under field conditions for the diagnosis of pediatric HIV-1 infection and the monitoring of pediatric antiretroviral therapy. (authors)

Composition of the ANRS 1201/1202 Ditrame Plus Study Group Principal Investigators: François Dabis, Valériane Leroy, Marguerite Timite-Konan, Christiane Welffens-Ekra. Coordination in Abidjan: Laurence Bequet, Didier K. Ekouevi, Besigin Tonwe-Gold, Ida Viho. Methodology, biostatistics and data management: Gérard Allou, Renaud Becquet, Katia Castetbon, Laurence Dequae-Merchadou, Charlotte Sakarovitch, Dominique Touchard. Clinical team: Clarisse Amani-Bosse, Ignace Ayekoe, Gédéon Bédikou, Nacoumba Coulibaly, Christine Danel, Patricia Fassinou, Apollinaire Horo, Ruffin Likikouët, Hassan Toure. Laboratory team: André Inwoley, François Rouet, Ramata Touré. Psycho-social team: Héléne Agbo, Hortense Aka-Dago, Hermann Brou, Annabel Desgrées-du-Loû, Alphonse Sihé, Annick Tijou-Traoré, Benjamin Zanou. Scientific Committee: Stéphane Blanche, Jean-François Delfraissy, Philippe Lepage, Laurent Mandelbrot, Christine Rouzioux, Roger Salamon; International audience; OBJECTIVE: In high HIV prevalence resource-constrained settings, exclusive breastfeeding with early cessation is one of the conceivable interventions aimed at the prevention of HIV through breast milk. Nevertheless, this intervention has potential adverse effects, such as the inappropriateness of complementary feeding to take over breast milk. The purpose of our study first was to describe the nature and the ages of introduction of complementary feeding among early weaned breastfed infants up to their first birthday and second was to assess the nutritional adequacy of these complementary foods by creating a child feeding index and to investigate its association with child nutritional status. METHODS: A prospective cohort study in Abidjan, C?d'Ivoire, was conducted in HIV-infected pregnant women who were willing to breastfeed and had received a perinatal antiretroviral prophylaxis. They were requested to practice exclusive breastfeeding and initiate early cessation of breastfeeding from the fourth month to reduce breast milk HIV transmission. Nature and ages of introductory complementary feeding were described in infants up to their first birthday by longitudinal compilation of 24-hour and 7-day recall histories. These recalls were done weekly until 6 weeks of age, monthly until 9 months of age, and then quarterly. We created an index to synthesize the nutritional adequacy of infant feeding practices (in terms of quality of the source of milk, dietary diversity, food, and meal frequencies) ranging from 0 to 12. The association of this feeding index with growth outcomes in children was investigated. RESULTS: Among the 262 breastfed children included, complete cessation of breastfeeding occurred in 77% by their first birthday, with a median duration of 4 months. Most of the complementary foods were introduced within the seventh month of life, except for infant food and infant formula that were introduced at age 4 months. The feeding index was relatively low (5 of 12) at age 6 months, mainly as a result of insufficient dietary diversity, but was improved in the next 6 months (8.5 of 12 at 12 months of age). Inadequate complementary feeding at age 6 months was associated with impaired growth during the next 12 months, with a 37% increased probability of stunting. CONCLUSION: Adequate feeding practices around the weaning period are crucial to achieving optimal child growth. HIV-infected women should turn to early cessation of breastfeeding only when they are counseled properly to provide adequate complementary feeding to take over breast milk. Our child feeding index could contribute to the assessment of the nutritional adequacy of complementary feeding around the weaning period and therefore help to detect children who are at risk for malnutrition.

International audience; OBJECTIVE: We assessed the uptake of a nutritional intervention promoting exclusive breast-feeding with early cessation between 3 and 4 months of age to reduce postnatal transmission of HIV in Abidjan, C?d'Ivoire. DESIGN: Between March 2001 and March 2003, HIV-infected pregnant women who had received perinatal antiretroviral prophylaxis were systematically offered prenatally 2 infant feeding interventions: artificial feeding or exclusive breast-feeding during 3 months and then early cessation of breast-feeding. Mother-infant pairs were closely followed for a period of 2 years, with continuous nutritional counseling and detailed collection of feeding practices. RESULTS: Among the 557 mothers enrolled, 262 (47%) initiated breast-feeding. Of these women, the probability of practicing exclusive breast-feeding from birth was 18% and 10% at 1 and 3 months of age, respectively. Complete cessation of breast-feeding was obtained in 45% and 63% by 4 and 6 months of age, respectively. Environmental factors such as living with a partner's family were associated with failure to initiate early cessation of breast-feeding. CONCLUSIONS: Acceptability of exclusive breast-feeding was low in this urban population. Shortening the duration of breast-feeding seemed to be feasible, however. Further investigations are ongoing to evaluate the safety and effectiveness of this intervention in reducing breast milk HIV transmission.

The Helsinki declaration is the reference statement of ethical principles to provide guidance to physicians and other participants in medical research involving human subjects. The main principle imposes on a physician the need to obtain an informed consent document from the research candidate before participating in a clinical trial. However this declaration does not take into account the sociocultural context of developing countries where the majority of the patients are illiterate. Obtaining the consent of study participants is thus often difficult and complex in resource-poor settings especially in the context of HIV infection. In March 2001 in Abidjan we launched the ANRS 1201/1202 Ditrame Plus open-label cohort to assess the field efficiency of a short-course combined regimen of zidovudine and nevirapine combined with alternatives to breastfeeding to prevent the mother-to-child transmission (MTCT) of HIV. We studied the level of understanding of the informed consent document in the HIV-1-infected women enrolled in this project. (excerpt)

The participation of HIV-1-infected pregnant women in a programme of prevention of mother-to-child transmission (MTCT) of HIV in Abidjan is described. Prenatal counselling with a rapid HIV test was proposed to 14 067 pregnant women and acceptance was 89.4%. The return rate for results was 74.2%. The HIV-1 prevalence was 11.1% and 26.2% of HIV-infected women started the prevention of MTCT programme. To increase the uptake we recommend community mobilization and the strengthening of male involvement. (authors)

Objectives: To describe acute retroviral syndrome and associated primary viraemia in African children infected with HIV-1 through breastfeeding. Design: Matched case–control study performed retrospectively within the ANRS 049 DITRAME project conducted in 1995–1998 in Abidjan Cote d’Ivoire. Methods: Cases were children infected by HIV-1 postnatally through breastfeeding. All were HIV-1 negative by DNA PCR at least 45 days of age but positive on a subsequent sample. This period was considered as surrounding the estimated date of postnatal contamination. Signs/symptoms occurring within this period were recorded in cases and compared with those occuring during the same time period in uninfected breastfed children (controls). For cases plasma specimens were tested for HIV-1 plasma RNA using the branched DNA assay. Results: Of 22 infants infected postnatally (median age at first positive sample 185 days; range 87–373 days) 21 (95.5%) exhibited at least one clinical sign compared with only 27 of the 44 (61.4%) uninfected children (P=0.003). Three independent factors were associated with primary HIV-1 infection: mononucleosis-like syndrome [odds ratio (OR) 8.3; 95% confidence interval (CI) 1.4–47.8] dermatitis (OR 6.0; CI 1.1–31.9) and generalized lymphadenopathy (OR 26.5; CI 2.0–348.4). Among cases initial median plasma HIV-1 RNA viral load was 5.92 log10 copies/ml; this declined to 4.96 log10 12 months after the first positive viral load. Conclusions: These results may be useful for the recognition of early pediatric cases of postnatal transmission in Africa and could enable targeting of those who should benefit from HIV RNA or DNA testing for primary HIV-1 infection and their subsequent care. (author’s)

OBJECTIVE: To ascertain the field acceptability and effectiveness of the routine utilization of zidovudine in reducing mother-to-child transmission (MTCT) of HIV in breastfed children after a randomized clinical trial demonstrated its efficacy in Cote d'Ivoire and Burkina Faso. METHODS: Pregnant women aged 18 years or older, who had confirmed HIV-1 infection, haemoglobinemia greater than 7 g/dl were enrolled in an open label cohort at 36-38 weeks' gestation to receive an oral short course of zidovudine. Paediatric HIV infection was defined as a positive HIV-1 polymerase chain reaction, or if aged 15 months or older, a positive HIV serology. RESULTS: The acceptability of HIV pretest counselling was significantly higher in the cohort (90.3%) than in the trial (83.7%) (P < 0.001), but the return rate for HIV test results and for inclusion was low. A similar proportion of women accepted starting zidovudine in the cohort, 30.4% compared with 27.3% in the trial (P = 0.13). The proportions of women who took more than 80% of the expected zidovudine regimen were 81.8% before labour, 86.7% during labour, and 88.1% during the postpartum period, compared with those observed during the trial, 78.1, 81.1, and 85%, respectively. The MTCT probability at age 15 months was 19.6% in the cohort (n = 185) versus 21.2% in the trial (P = 0.52). CONCLUSION: The major drawback with the implementation of a short zidovudine regimen to reduce MTCT is HIV counselling and testing procedures. For women who consent, zidovudine is well accepted and efficacious under routine circumstances.

The aim of this paper is to describe the adherence of African HIV+ women to the counselling provided after announcement of the result of the HIV test during pregnancy, focusing on early weaning to reduce post-natal transmission, protected sexual intercourse to avoid sexual transmission, and contraceptive use to avoid unexpected pregnancies. In 1999-2000, a questionnaire on sexual and reproductive behaviours was administered to 149 HIV+ women followed in post-partum, informed and counselled in the ANRS 049 DITRAME project in Abidjan. Côte d'Ivoire. Duration of breastfeeding, post-partum amenorrhea and abstinence, contraceptive use and condom use were measured. Incidence of pregnancies during the first 24 months post partum was estimated and modelled by a Cox regression model. Average duration of breastfeeding was 7.9 months, average duration of post partum abstinence was 12.0 months, and 39% of women used contraceptives at the time of the survey. Frequency of condom use was 13%. Incidence of pregnancies was 16.5 per 100 women-years at risk. Half of these pregnancies were not desired and a third were terminated by induced abortion. The significant determinants of the pregnancy occurrence were the death of the previous child, the cessation of breastfeeding, the cessation of the post partum abstinence, and higher education. In conclusion, if counselling on early weaning can be followed by the HIV+ women, it is not easily the case for condom and contraceptive use. Hence, pregnancy incidence in the post-partum follow-up was high. The main strategy of these HIV+ women to avoid unexpected pregnancies as well as sexual transmission of HIV seems to be an increase of the duration of post-partum abstinence. The most educated women who cannot easily adopt this strategy are particularly exposed to unwanted pregnancies.

OBJECTIVES: To study mortality in African children born to HIV-1-infected mothers exposed peripartum to zidovudine. METHODS: A randomized placebo-controlled trial in Abidjan and Bobo-Dioulasso. Pregnant women received either 300 mg zidovudine twice daily from 36-38 weeks' gestation, 600 mg during labour, and 300 mg twice daily for 7 days post-partum or a matching placebo. Determinants of mortality were studied up to 18 months, overall and among the infected children: treatment, centre, timing of infection, mother and child HIV disease. RESULTS: There were 75 infant deaths among 407 live births. The risk of death at 18 months was 176/1000 in the zidovudine arm and 221 for placebo. Relative hazard (RH, zidovudine versus placebo) was 0.47 [95% confidence interval (CI) 0.2-1.0] up to 230 days of life. Maternal CD4 lymphocyte count < 200/mm3 (RH 2.92; CI 1.4-6.1) and child HIV-1 infection (RH 12.6; CI 6.6-24.3) increased mortality of all children born to HIV-1-infected mothers. There were 101 children infected (40 in the zidovudine group), and 51 died. Their 18 month probability of death was 590/1000 in the zidovudine group and 510 in the placebo group. Among infected children, maternal zidovudine reduced the risk of death on or before day 230 (RH 0.18; CI 0.1-0.5). Maternal CD4 lymphocyte count < 200/mm3 (RH 3.25; CI 1.3-8.4), maternal death (RH 9.65; CI 1.7-56.0), diagnosis of paediatric infection on or before day 12 (RH 18.1; CI 4.8-69.0) and between days 13 and 45 (RH 7.63; CI 2.0-29.5), clinical paediatric AIDS (RH 5.37; CI 2.3-12.7) were risk factors for death in HIV-1-infected children. CONCLUSION: Mother-to-child transmission reduction by zidovudine is safe and beneficial to African children. The mortality of HIV-1-infected children is high. Peripartum maternal zidovudine exerts a protective effect for at least 8 months.

The reproductive histories of 1201 consecutive women attending a prenatal clinic in Abidjan Ivory Coast in 1997 were investigated to determine whether HIV-infected women become pregnant less often than HIV-negative women. This issue is important because if HIV-positive women have fewer pregnancies or more miscarriages than other women then women who visit antenatal clinics are not representative of all women of childbearing age and HIV prevalence is underestimated at these centers. All women were unaware of their HIV status at study entry. 169 women (14.3%) were HIV-positive but it was not possible to determine whether the pregnancies occurred before or after infection. The mean age at first coitus was 16 years among HIV-positive and 17 years among HIV-negative women. The mean number of pregnancies was higher among HIV-positive women under 20 years of age than HIV-negative women of this age (2.1 vs. 1.7) but this trend was reversed from age 25 years onward (4.2 vs. 4.7). The interval between the last two pregnancies was longer among HIV-infected women than uninfected women (36.4 vs. 33 months). The gap was greatest among women 25-29 years of age (51.8 vs. 35.7 months). In multivariate analysis after adjustment for age last pregnancy outcome duration of postpartum amenorrhea use of contraceptives during this interval marital status and educational level HIV infection significantly delayed the occurrence of the current pregnancy (Cox model hazard ratio 0.83; 95% confidence interval 0.69-0.99). Since HIV infection appears to compromise physiologic ability to become pregnant HIV prevalence assessed at antenatal centers should be adjusted for the fertility differences between HIV-positive and HIV-negative women.

Before implementation of a tolerance and efficacy trial of zidovudine (ZDV) in Abidjan Ivory Coast the acceptability of HIV screening was probed among women attending the Yopougon Health Center for their first prenatal visit in 1996-97. Of the 2219 prenatal clients who were eligible for AZT 395 (17.8%) refused HIV testing--primarily because of fear of the result. Of the 1824 women who consented to testing 279 (15.3%) were HIV-positive (249 for HIV-1 21 for HIV-2 and 9 with dual reactions). 204 HIV-positive women returned for their test result. Of these women 3 refused the confirmation test and 29 were lost to follow-up after the second test leaving 172 women for pre-inclusion. However 101 of these women were subsequently excluded for reasons including return visit too late in pregnancy for AZT planned delivery outside of Abidjan change of mind and loss to follow-up before formal inclusion. Thus only 71 women received the trial treatment. The only significant difference between these 71 women and those who did not complete the selection process was that the former women were older (mean age 26 years) than the latter (mean age 24 years). The finding that it was necessary to perform HIV tests in 1824 women to recruit 71 women for a clinical trial of ZDV indicates a need for IEC campaigns aimed at women of childbearing age about maternal-child HIV transmission and its prevention.

Objective. To describe plasma human immunodeficiency virus type 1 (HIV-1) RNA levels in African HIV-1-infected children in relation to the timing of infection and disease progression. Methods. A retrospective cohort study was conducted of 80 children who were born to HIV-1-positive mothers and clinically followed from birth to 18 months of age in the ANRS 049 Ditrame project, Abidjan, Côte d’Ivoire (West Africa). The diagnosis and timing of pediatric HIV-1 infection were determined prospectively according to HIV-1 DNA polymerase chain reaction results. A total of 364 HIV-1 RNA viral load (VL) measurements were assessed retrospectively. Kaplan-Meier analyses and proportional hazards models were used to evaluate the prognostic value of pediatric VL and covariates for HIV disease progression or death. Results. Mean initial positive VL was significantly lower among children who were infected in utero (4.94 log10/mL, n = 12) than in children who were infected later (5.6–6.1 log10/mL, n = 68). In the first 6 months after diagnosis, HIV-1 RNA levels peaked (≥6 log10/mL), regardless of timing of infection. Then, a slow decline (overall slope, −0.076 log10 copies/mL/mo) was observed until 18 months of age. A 1 log10 higher value of the pediatric peak VL (risk ratio [RR]: 1.85; 95% confidence interval [CI]: 1.0–3.44) and of the maternal VL at delivery (RR: 1.90; CI: 1.16–3.12) were independently associated with an increased risk of rapid progression to acquired immune deficiency syndrome (AIDS) or death at 18 months of life (23 AIDS diagnoses and 31 deaths). Disease progression or death was more rapid for girls than for boys (RR: 2.26; CI: 1.39–4.96). Conclusions. In Africa, pediatric HIV-1 RNA levels are very close to those described in industrialized countries and seem to be predictive of AIDS stage or death, as in industrialized countries. With antiretroviral therapy becoming more widely available, the early identification and monitoring of pediatric HIV disease remains of paramount importance in Africa.

Background: In resource-limited settings, many HIV-infected patients are lost to follow-up (LTF) before starting ART; risk factors among those not eligible for ART at enrollment into care are not well described. Methods: We examined data from 4,278 adults (3,613 women, 665 men) enrolled in HIV care through March 2007 in the MTCT-Plus Initiative with a CD4 count ≥200 cells/mm3 and WHO stage ≤ 2 at enrollment. Patients were considered LTF if > 12 months elapsed since their last clinic visit. Gender-specific Cox regression models were used to assess LTF risk factors. Results: The proportion LTF was 8.2 % at 12 months following enrollment, and was higher among women (8.4 %) than men (7.1 %). Among women, a higher risk of LTF was associated with younger age (adjusted hazard ratio [AHR]15–19/30+: 2.8, 95 % CI:2.1-3.6; AHR20–24/30+:1.9, 95 % CI:1.7-2.2), higher baseline CD4 count (AHR350–499/200–349:1.5; 95 % CI:1.0-2.1; AHR500+/200–349:1.5; 95 % CI:1.0-2.0), and being pregnant at the last clinic visit (AHR:1.9, 95 % CI:1.4-2.5). Factors associated with a lower risk of LTF included, employment outside the home (AHR:0.73, 95 % CI:0.59-0.90), co-enrollment of a family/household member (AHR:0.40, 95 % CI:0.26-0.61), and living in a household with ≥4 people (AHR:0.74, 95 % CI:0.64-0.85). Among men, younger age (AHR15–19/30+: 2.1, 95 % CI:1.2-3.5 and AHR30–34/35+:1.5, 95 % CI:1.0-2.4) had a higher risk of LTF. Electricity in the home (AHR:0.61, 95 % CI:0.41-0.91) and living in a household with ≥4 people (AHR:0.58, 95 % CI:0.39-0.85) had a lower risk of LTF. Conclusions: Socio-economic status and social support may be important determinants of retention in patients not yet eligible for ART. Among women of child-bearing age, strategies around sustaining HIV care during and after pregnancy require attention. Keywords HIV AIDS Anti-retroviral therapy Pre-ART, Lost to follow up Risk factors Social support