Maternal Antiretroviral Therapy for the Prevention of Mother-To-Child Transmission of HIV in Malawi: Maternal and Infant Outcomes Two Years after Delivery

Abstract

BackgroundOptimized preventive strategies are needed to reach the objective of eliminating pediatric AIDS. This study aimed to define the determinants of residual HIV transmission in the context of maternal antiretroviral therapy (ART) administration to pregnant women, to assess infant safety of this strategy, and to evaluate its impact on maternal disease.Methodology/Principal FindingsA total of 311 HIV-infected pregnant women were enrolled in Malawi in an observational study and received a nevirapine-based regimen from week 25 of gestation until 6 months after delivery (end of breastfeeding period) if their CD4+ count was > 350/mm3 at baseline (n = 147), or indefinitely if they met the criteria for treatment (n. 164). Mother/child pairs were followed until 2 years after delivery. The Kaplan-Meier method was used to estimate HIV transmission, maternal disease progression, and survival at 24 months. The rate of HIV infant infection was 3.2% [95% confidence intervals (CI) 1.0-5.4]. Six of the 8 transmissions occurred among mothers with baseline CD4+ count > 350/mm3. HIV-free survival of children was 85.8% (95% CI 81.4-90.1). Children born to mothers with baseline CD4+ count < 350/mm3 were at increased risk of death (hazard ratio 2.6, 95% CI 1.1-6.1). Among women who had stopped treatment the risk of progression to CD4+ count < 350/mm3 was 20.6% (95% CI 9.2-31.9) by 18 months of drug discontinuation.ConclusionsHIV transmission in this cohort was rare however, it occurred in a significative proportion among women with high CD4+ counts. Strategies to improve treatment adherence should be implemented to further reduce HIV transmission. Mortality in the uninfected exposed children was the major determinant of HIV-free survival and was associated to maternal disease stage. Given the considerable proportion of women reaching the criteria for treatment within 18 months of drug discontinuation, life-long ART administration to HIV-infected women should be considered.

Temporal changes in the outcomes of HIV-exposed infants in Kinshasa, Democratic Republic of Congo during a period of rapidly evolving guidelines for care (2007–2013)

“…One study of 561 infants who received care between 2009 and 2012 in the Kilimanjaro Region of Tanzania reported 10% mother-to-child HIV transmission [25], despite the provision of prophylactic regimens that were expected to reduce vertical transmission to below 5% [12]. Another study of 311 mother–infant pairs in Malawi was able to reduce transmission to 3%, but 14% of infants died by 24 months of age [26]. …”

Weight Changes During and After 6 Months of Breastfeeding in HIV-Infected Mothers Receiving Antiretroviral Therapy in Malawi

“…However, the latter finding was not confirmed in a subsequent study (conducted in the same country on 300 women), which confirmed that BMI decreased more rapidly in breastfeeding women compared to those not breastfeeding, but showed that mortality did not differ significantly between formula feeders and breastfeeding mothers. 5 The very low mortality rate of women in our cohort (2.1% 2 years postpartum) 8 prevented us from assessing any possible difference in subsequent survival, but also suggested no major negative mortality impact.…”

“…Patient population included women enrolled in the SMAC (Safe Milk for African Children) study, 8 conducted in Malawi between 2008 and 2011, within the DREAM program of the Community of S. Egidio, an Italian faith-based nongovernmental organization. In the study, aimed to assess the safety and pharmacokinetics of ART administration during breastfeeding, ART-naive women (with no grade 3 or 4 laboratory toxicity and no active tuberculosis) received either zidovudine plus lamivudine and nevirapine (n = 126) or stavudine plus lamivudine and nevirapine (n = 143) from week 25 of gestation until 6 months postpartum if their CD4 + count was > 350/mm 3 at baseline, or indefinitely if they met the criteria for treatment.…”

Lack of new HBV infections over 2 years of follow-up in HIV-positive women receiving ART up to 6 or 24 months after delivery

“…Women enrolled in the Safe Milk for African Children (SMAC) [9] observational study, conducted in Malawi between 2008 and 2011 to evaluate safety of antiretroviral administration during pregnancy and breastfeeding, were studied.…”