Risk factors for loss to follow-up prior to ART initiation among patients enrolling in HIV care with CD4+ cell count ≥200 cells/µL in the multi-country MTCT-Plus Initiative.

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/mm(3) 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.

Beneficial effects of offering prenatal HIV counselling and testing on developing a HIV preventive attitude among couples. Abidjan, 2002-2005.

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, Côte 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.

Maternal 12-month response to antiretroviral therapy following prevention of mother-to-child transmission of HIV type 1, Ivory Coast, 2003-2006.

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 <200 cells/mm(3) (aOR, 0.3; 95% CI, 0.2-0.8). NVP resistance was not associated with virological failure (aOR, 1.8; 95% CI, 0.5-6.5). CONCLUSIONS: Our study found that poor adherence and 3TC resistance acquired after the intervention to prevent mother-to-child transmission of HIV infection were associated with virologic failure in women who initiated antiretroviral treatment.

When do HIV-infected women disclose their HIV status to their male partner and why? A study in a PMTCT programme, Abidjan.

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.

Two-year morbidity-mortality and alternatives to prolonged breast-feeding among children born to HIV-infected mothers in Côte d'Ivoire.

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, Côte 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.

Antiretroviral treatment and prevention of peripartum and postnatal HIV transmission in West Africa: evaluation of a two-tiered approach.

BACKGROUND: Highly active antiretroviral treatment (HAART) has only been recently recommended for HIV-infected pregnant women requiring treatment for their own health in resource-limited settings. However, there are few documented experiences from African countries. We evaluated the short-term (4 wk) and long-term (12 mo) effectiveness of a two-tiered strategy of prevention of mother-to-child transmission of HIV (PMTCT) in Africa: women meeting the eligibility criteria of the World Health Organization (WHO) received HAART, and women with less advanced HIV disease received short-course antiretroviral (scARV) PMTCT regimens. METHODS AND FINDINGS: The MTCT-Plus Initiative is a multi-country, family-centred HIV care and treatment program for pregnant and postpartum women and their families. Pregnant women enrolled in Abidjan, Côte d'Ivoire received either HAART for their own health or short-course antiretroviral (scARV) PMTCT regimens according to their clinical and immunological status. Plasma HIV-RNA viral load (VL) was measured to diagnose peripartum infection when infants were 4 wk of age, and HIV final status was documented either by rapid antibody testing when infants were aged > or = 12 mo or by plasma VL earlier. The Kaplan-Meier method was used to estimate the rate of HIV transmission and HIV-free survival. Between August 2003 and June 2005, 107 women began HAART at a median of 30 wk of gestation, 102 of them with zidovudine (ZDV), lamivudine (3TC), and nevirapine (NVP) and they continued treatment postpartum; 143 other women received scARV for PMTCT, 103 of them with sc(ZDV+3TC) with single-dose NVP during labour. Most (75%) of the infants were breast-fed for a median of 5 mo. Overall, the rate of peripartum HIV transmission was 2.2% (95% confidence interval [CI] 0.3%-4.2%) and the cumulative rate at 12 mo was 5.7% (95% CI 2.5%-9.0%). The overall probability of infant death or infection with HIV was 4.3% (95% CI 1.7%-7.0%) at age week 4 wk and 11.7% (95% CI 7.5%-15.9%) at 12 mo. CONCLUSIONS: This two-tiered strategy appears to be safe and highly effective for short- and long-term PMTCT in resource-constrained settings. These results indicate a further benefit of access to HAART for pregnant women who need treatment for their own health.

Variation of CD4 count and percentage during pregnancy and after delivery: implications for HAART initiation in resource-limited settings.

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, Côte 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 <200 cells/mm(3) and 14.8 % had a CD4 percentage <15%. One month after delivery, the median CD4 count was 489 cells/mm(3) (vs. baseline: p < 0.001), the median CD4 percentage was 25.6% (vs. baseline: p = 0.107), 9.5% of women had CD4 count <200 cells/mm(3) (vs. baseline: p < 0.001), and 15.1% of women had a CD4 percentage <15% (vs. baseline: p = 0.823). When combining the CD4 count and the WHO clinical stage, the proportion of women who met the WHO 2006 criteria for initiating HAART was 28.3% at baseline but 17.2% only at 1 month after delivery (p < 0.001). Between the prepregnancy and the postdelivery periods, the CD4 count experienced a significant increase, whereas the CD4 percentage remained unchanged. To accurately target the most appropriate time to start HAART, the CD4 percentage could be more reliable than the absolute count in sub-Saharan African pregnant women.

Decrease of human immunodeficiency virus prevalence in antenatal clinics in Abidjan, Côte d'Ivoire, 1995-2002.

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).

Field efficacy of zidovudine, lamivudine and single-dose nevirapine to prevent peripartum HIV transmission.

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 > or =36 weeks of gestation, with 600 mg of ZDV + 200 mg NVPsd orally at beginning of labour. In 2002-2003, the antepartum regimen at > or =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 > or = 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.

Primary HIV-1 infection in African children infected through breastfeeding.

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, Côte 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 occurring 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 paediatric 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.

Field acceptability and effectiveness of the routine utilization of zidovudine to reduce mother-to-child transmission of HIV-1 in West Africa.

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 Côte 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.

Contraceptive use, protected sexual intercourse and incidence of pregnancies among African HIV-infected women. DITRAME ANRS 049 Project, Abidjan 1995-2000.

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.

Early mixed feeding and breastfeeding beyond 6 months increase the risk of postnatal HIV transmission: ANRS 1201/1202 Ditrame Plus, Abidjan, Côte d'Ivoire.

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<0.001). In adjusted analysis, breastfeeding for more than 6 months and mixed feeding during the first month of life were independently associated with a 7.5 (AOR 95% CI, 2.0-28.2, p=0.003)- and a 6.3 (95% CI, 1.1-36.4, p=0.04)-fold increase of postnatal transmission among breastfed children. CONCLUSIONS: Mixed feeding during the first month of life and breastfeeding beyond 6 months are strong determinants of HIV transmission and should be avoided when replacement feeding after breastfeeding cessation can be safely and sustainably provided.

18-month effectiveness of short-course antiretroviral regimens combined with alternatives to breastfeeding to prevent HIV mother-to-child transmission.

OBJECTIVE: We assessed the 18-month effectiveness of short-course (sc) antiretroviral peripartum regimens combined with alternatives to prolonged breastfeeding to prevent mother-to-child transmission (MTCT) of HIV-1 in Abidjan, Côte d'Ivoire. METHODOLOGY: HIV-1 infected pregnant women received from >/=32-36 weeks of gestation scZidovudine (ZDV)+/-Lamivudine (3TC)+single-dose Nevirapine (sdNVP) at delivery within the ANRS 1201/1202 DITRAME-Plus cohort (2001-2003). Neonates received a sdNVP+7-day ZDV prophylaxis. Two infant-feeding interventions were systematically offered free of charge: formula-feeding or exclusive shortened breastfeeding with early cessation from four months. The reference group was the ANRS 049a DITRAME cohort (1994-2000) exposed to scZDV from 36 weeks, then to prolonged breastfeeding. Pediatric HIV infection was defined by a positive plasma HIV-1 RNA at any age, or if aged >/=18 months, a positive HIV-1 serology. Turnbull estimates of cumulative transmission risks (CTR) and effectiveness (HIV-free survival) were compared by exposure group using a Cox model. FINDINGS: Among 926 live-born children enrolled, 107 (11.6%) were HIV-infected at 18 months. CTRs were 22.3% (95% confidence interval[CI]:16-30%) in the 238 ZDV long-term breastfed reference group, 15.9% (CI:10-27%) in the 169 ZDV+sdNVP shortened breastfed group; 9.4% (CI:6-14%) in the 195 ZDV+sdNVP formula-fed group; 6.8% (CI:4-11%) in the 198 ZDV+3TC+sdNVP shortened breastfed group, and 5.6% (CI:2-10%) in the 126 ZDV+3TC+sdNVP formula-fed group. Each combination had a significantly higher effectiveness than the ZDV long-term breastfed group except for ZDV+sdNVP shortened breastfed children, ranging from 51% (CI:20-70%) for ZDV+sdNVP formula fed children to 63% (CI:40-80%) for ZDV+3TC+NVPsd shortened breastfed children, after adjustment for maternal eligibility for antiretroviral therapy (ART), home delivery and low birth-weight. Substantial MTCT risk reductions are reachable in Africa, even in short-term breastfed children. The two sc antiretroviral combinations associated to any of the two infant feeding interventions, formula-feeding and shortened breastfeeding, reduce significantly MTCT with long-term benefit until age 18 months and without increasing mortality.

Acceptability of formula-feeding to prevent HIV postnatal transmission, Abidjan, Côte d'Ivoire: ANRS 1201/1202 Ditrame Plus Study.

OBJECTIVE: To describe the maternal acceptability of formula-feeding proposed to reduce postnatal HIV transmission in Abidjan, Côte d'Ivoire. METHODS: Each consenting HIV-infected pregnant women, age > or =18 years, who received a perinatal antiretroviral prophylaxis was eligible. Two hierarchical infant-feeding options were proposed antenatally: exclusive formula-feeding or short-term exclusive breast-feeding. Formula-feeding was provided free up to age 9 months. Determinants of acceptability were analyzed using a logistic regression. Formula-feeding failure was defined as having breast-fed one's child at least once. RESULTS: Between March 2001 and March 2003, 580 women delivered: 97% expressed their infant-feeding choice before delivery; 53% chose formula-feeding. Significant prenatal determinants for refusing formula-feeding were: living with her partner, being Muslim, having a low educational level, being followed in one of the study sites, having not disclosed her HIV status, and having been included within the first 6 months of the project. Among the 295 mothers who formula-fed, the Kaplan-Meier probability of success of the formula-feeding option was 93.6% at Day 2 (95% confidence interval [CI]: 90.7% to 96.3%) and 84.2% at 12 months (95% CI: 79.9% to 88.5%): 46 of 295 (15.6%) women breast-fed at least once, of whom 41% temporarily practiced mixed-feeding at Day 2 because of social stigma or newborn poor health. CONCLUSIONS: In settings with general access to clean water, structured antenatal counseling, and sustained provision of free formula, slightly over half of HIV-infected women chose to artificially feed their newborn infant. Low mixed-feeding rates were observed. This social acceptability must be balanced with mother-child long-term health outcomes to guide safe recommendations on infant-feeding among HIV-infected women in African urban settings.

Impact of nevirapine (NVP) plasma concentration on selection of resistant virus in mothers who received single-dose NVP to prevent perinatal human immunodeficiency virus type 1 transmission and persistence of resistant virus in their infected children.

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.

Transmission rates in consecutive pregnancies exposed to single-dose nevirapine in Soweto, South Africa and Abidjan, Côte d'Ivoire.

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 Côte 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.

Complementary feeding adequacy in relation to nutritional status among early weaned breastfed children who are born to HIV-infected mothers: ANRS 1201/1202 Ditrame Plus, Abidjan, Cote d'Ivoire.

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, Côte 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.

CD4 percentages and total lymphocyte counts as early surrogate markers for pediatric HIV-1 infection in resource-limited settings.

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, Côte d'Ivoire) 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.

Serum lactate levels in infants exposed peripartum to antiretroviral agents to prevent mother-to-child transmission of HIV: Agence Nationale de Recherches Sur le SIDA et les Hépatites Virales 1209 study, Abidjan, Ivory Coast.

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 > or = 2.5 mmol/L, defining hyperlactatemia, were observed in 39 of the 292 infants who had > or = 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.