Renaud Becquet

Antiretroviral therapy in pregnant women with advanced HIV disease and pregnancy outcomes in Abidjan, Côte d'Ivoire.

Background:Pregnancy outcomes in women receiving highly active antiretroviral treatment (HAART) in Africa are not well described. Methods:HIV-1-infected pregnant women in the ANRS Ditrame Plus and the MTCT-Plus projects were included. Between March 2001 and July 2003, when HAART was not yet available, women eligible for HAART received a short-course antiretroviral regimen, zidovudine (ZDV) or (ZDV + lamivudine) and single dose of nevirapine for preventing mother-to-child transmission (PMTCT group). Between August 2003 and August 2007, eligible women for HAART received it (HAART group). The frequencies of low birth weight (LBW) (<2500 g), stillbirth and infant mortality are reported. Risk factors associated with LBW were investigated using a logistic regression model. Results:Of the 326 HIV-infected pregnant women, 175 women received short-course antiretroviral (median CD4 cell count 177 cells/μl) and 151 received HAART (median CD4 cell count 182 cells/μl). At 12 months, three paediatric infections (2.3%) occurred in the HAART group vs. 25 (16.1%) in the PMTCT group (P < 0.001). The rate of LBW was 22.3% in the HAART group and 12.4% in the PMTCT group (P = 0.02). In multivariable analysis (n = 309), after adjustment on maternal CD4 cell count, WHO stage, age and maternal BMI, HAART initiated before pregnancy [adjusted odds ratio (OR) 2.88, 95% confidence interval (CI) 1.10–7.51] and during pregnancy (adjusted OR 2.12, 95% CI 1.15–4.65) and maternal BMI at delivery (adjusted OR 2.43, 95% CI 1.20–4.91) were associated with LBW. Conclusion:HAART in pregnant African women with advanced HIV disease substantially reduced mother-to-child transmission, but was associated with LBW.

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 womens 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 (χ2 = 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 (χ2 = 10.04, df = 1, p = 0.002). Partners of HIV-positive women who were informed of their wifes HIV status were more likely to undertake HIV testing than those not informed (37.7% versus 10.5%, χ2 = 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 womens adherence to the advice given to prevent postnatal and sexual HIV transmission.

Net survival of perinatally and postnatally HIV-infected children: a pooled analysis of individual data from sub-Saharan Africa.

BACKGROUND Previously, HIV epidemic models have used a double Weibull curve to represent high initial and late mortality of HIV-infected children, without distinguishing timing of infection (peri- or post-natally). With more data on timing of infection, which may be associated with disease progression, a separate representation of children infected early and late was proposed. METHODS Paediatric survival post-HIV infection without anti-retroviral treatment was calculated using pooled data from 12 studies with known timing of HIV infection. Children were grouped into perinatally or post-natally infected. Net mortality was calculated using cause-deleted life tables to give survival as if HIV was the only competing cause of death. To extend the curve beyond the available data, children surviving beyond 2.5 years post infection were assumed to have the same survival as young adults. Double Weibull curves were fitted to both extended survival curves to represent survival of children infected perinatally or through breastfeeding. RESULTS Those children infected perinatally had a much higher risk of dying than those infected through breastfeeding, even allowing for background mortality. The final-fitted double Weibull curves gave 75% survival at 5 months after infection for perinatally infected, and 1.1 years for post-natally infected children. An estimated 25% of the early infected children would still be alive at 10.6 years compared with 16.9 years for those infected through breastfeeding. CONCLUSIONS The increase in available data has enabled separation of child mortality patterns by timing of infection allowing improvement and more flexibility in modelling of paediatric HIV infection and survival.

Preventing postnatal transmission of HIV-1 through breast-feeding: modifying infant feeding practices.

Approaches to reducing or preventing the risk of postnatal transmission through breast-feeding include the avoidance of all breast-feeding and the use of exclusive replacement feeds or exclusive breast-feeding for a limited duration with early and rapid cessation of breast-feeding around 4-6 months of age. The efficacy and safety of the latter approach have not been established and studies are in progress to provide further information. In addition, inactivation of HIV in breast milk would allow breast-feeding to continue while reducing the risk of postnatal transmission of HIV and may be usefully applied in certain circumstances, such as for premature infants or while a mother recovers from mastitis. In this review, experience is reported from clinical trials or studies additional to their main objective of assessing rates and risk factors for mother-to-child transmission. This may inform policy, programming, and training options and may be especially valuable in the absence of conclusive data on the efficacy of the interventions to be applied during the breast-feeding period.

Children Who Acquire HIV Infection Perinatally Are at Higher Risk of Early Death than Those Acquiring Infection through Breastmilk: A Meta-Analysis

Background Assumptions about survival of HIV-infected children in Africa without antiretroviral therapy need to be updated to inform ongoing UNAIDS modelling of paediatric HIV epidemics among children. Improved estimates of infant survival by timing of HIV-infection (perinatally or postnatally) are thus needed. Methodology/Principal Findings A pooled analysis was conducted of individual data of all available intervention cohorts and randomized trials on prevention of HIV mother-to-child transmission in Africa. Studies were right-censored at the time of infant antiretroviral initiation. Overall mortality rate per 1000 child-years of follow-up was calculated by selected maternal and infant characteristics. The Kaplan-Meier method was used to estimate survival curves by childs HIV infection status and timing of HIV infection. Individual data from 12 studies were pooled, with 12,112 children of HIV-infected women. Mortality rates per 1,000 child-years follow-up were 39.3 and 381.6 for HIV-uninfected and infected children respectively. One year after acquisition of HIV infection, an estimated 26% postnatally and 52% perinatally infected children would have died; and 4% uninfected children by age 1 year. Mortality was independently associated with maternal death (adjusted hazard ratio 2.2, 95%CI 1.6–3.0), maternal CD4<350 cells/ml (1.4, 1.1–1.7), postnatal (3.1, 2.1–4.1) or peri-partum HIV-infection (12.4, 10.1–15.3). Conclusions/Results These results update previous work and inform future UNAIDS modelling by providing survival estimates for HIV-infected untreated African children by timing of infection. We highlight the urgent need for the prevention of peri-partum and postnatal transmission and timely assessment of HIV infection in infants to initiate antiretroviral care and support for HIV-infected children.

The Spectrum projection package: improvements in estimating incidence by age and sex, mother-to-child transmission, HIV progression in children and double orphans.

Background The Spectrum program is used to estimate key HIV indicators from the trends in incidence and prevalence estimated by the Estimation and Projection Package or the Workbook. These indicators include the number of people living with HIV, new infections, AIDS deaths, AIDS orphans, the number of adults and children needing treatment, the need for prevention of mother-to-child transmission and the impact of antiretroviral treatment on survival. The UNAIDS Reference Group on Estimates, Models and Projections regularly reviews new data and information needs, and recommends updates to the methodology and assumptions used in Spectrum. Methods The latest update to Spectrum was used in the 2009 round of global estimates. This update contains new procedures for estimating: the age and sex distribution of adult incidence, new child infections occurring around delivery or through breastfeeding, the survival of children by timing of infection and the number of double orphans.

Universal Antiretroviral Therapy for Pregnant and Breast-Feeding HIV-1-Infected Women: Towards the Elimination of Mother-to-Child Transmission of HIV-1 in Resource-Limited Settings

Prevention of mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) remains a challenge in most resource-limited settings, particularly in Africa. Single-dose and short-course antiretroviral (ARV) regimens are only partially effective and have failed to achieve wide coverage despite their apparent simplicity. More potent ARV combinations are restricted to pregnant women who need treatment for themselves and are also infrequently used. Furthermore, postnatal transmission via breast-feeding is a serious additional threat. Modifications of infant feeding practices aim to reduce HIV-1 transmission through breast milk; replacement feeding is neither affordable nor safe for the majority of African women, and early breast-feeding cessation (eg, prior to 6 months of life) requires substantial care and nutritional counseling to be practiced safely. The recent roll out of ARV treatment has changed the paradigm of prevention of MTCT. To date, postnatal ARV interventions that have been evaluated target either maternal ARV treatment to selected breast-feeding women, with good efficacy, or single-drug postexposure prophylaxis for short periods of time to their neonates, with a partial efficacy and at the expense of acquisition of drug-related viral resistance. We hypothesize that a viable solution to eliminate pediatric AIDS lies in the universal provision of fully suppressive ARV regimens to all HIV-1-infected women through pregnancy, delivery, and the entire breast-feeding period. On the basis of available evidence, we suggest translating into practice the recently available evidence on this matter without any further delay.

Infant feeding, HIV transmission and mortality at 18 months: the need for appropriate choices by mothers and prioritization within programmes

Objectives: To determine the late HIV transmission and survival risks associated with early infant feeding practices. Design: A nonrandomized intervention cohort. Methods: HIV-infected pregnant women were supported in their infant feeding choices. Infant feeding data were obtained weekly; blood samples from infants were taken monthly to diagnose HIV infection. Eighteen-month mortality and HIV transmission risk were assessed according to infant feeding practices at 6 months. Results: One thousand one hundred and ninety-three live-born infants were included. Overall 18-month probabilities of death (95% confidence interval) were 0.04 (0.03–0.06) and 0.53 (0.46–0.60) for HIV-uninfected and HIV-infected children, respectively. The eighteen-month probability of survival was not statistically significantly different for HIV-uninfected infants breastfed or replacement fed from birth. In univariate analysis of infant feeding practices, the probability of HIV-free survival beyond the first 6 months of life in children alive at 6 months was 0.98 (0.89–1.00) amongst infants replacement fed from birth, 0.96 (0.90–0.98; P = 0.25) and 0.91 (0.87–0.94; P = 0.03) in those breastfed for less or more than 6 months, respectively. In multivariable analyses, maternal unemployment and low antenatal CD4 cell count were independently associated with more than three-fold increased risk of infant HIV infection or death. Conclusion: Breastfeeding and replacement feeding of HIV-uninfected infants were associated with similar mortality rates at 18 months. However, these findings were amongst mothers and infants who received excellent support to first make, and then practice, appropriate infant feeding choices. For programmes to achieve similar results, the quality of counselling and identification of mothers with low CD4 cell count need to be the targets of improvement strategies.

Implementing family-focused HIV care and treatment: the first 2 years' experience of the mother-to-child transmission-plus program in Abidjan, Côte d'Ivoire.

Objectives  To describe a family‐focused approach to HIV care and treatment and report on the first 2 years experience of implementing the mother‐to‐child transmission (MTCT)‐plus program in Abidjan, Côte d’Ivoire.

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.