Efficacy of WHO recommendation for continued breastfeeding and maternal cART for prevention of perinatal and postnatal HIV transmission in Zambia.

INTRODUCTION: To prevent mother-to-child transmission (MTCT) of HIV in developing countries, new World Health Organization (WHO) guidelines recommend maternal combination antiretroviral therapy (cART) during pregnancy, throughout breastfeeding for 1 year and then cessation of breastfeeding (COB). The efficacy of this approach during the first six months of exclusive breastfeeding has been demonstrated, but the efficacy of this approach beyond six months is not well documented. METHODS: A prospective observational cohort study of 279 HIV-positive mothers was started on zidovudine/3TC and lopinavir/ritonavir tablets between 14 and 30 weeks gestation and continued indefinitely thereafter. Women were encouraged to exclusively breastfeed for six months, complementary feed for the next six months and then cease breastfeeding between 12 and 13 months. Infants were followed for transmission to 18 months and for survival to 24 months. Text message reminders and stipends for food and transport were utilized to encourage adherence and follow-up. RESULTS: Total MTCT was 9 of 219 live born infants (4.1%; confidence interval (CI) 2.2-7.6%). All breastfeeding transmissions that could be timed (5/5) occurred after six months of age. All mothers who transmitted after six months had a six-month plasma viral load >1,000 copies/ml (p<0.001). Poor adherence to cART as noted by missed dispensary visits was associated with transmission (p=0.04). Infant mortality was lower after six months of age than during the first six months of life (p=0.02). The cumulative rate of infant HIV infection or death at 18 months was 29/226 (12.8% 95 CI: 7.5-20.8%). CONCLUSIONS: Maternal cART may limit MTCT of HIV to the UNAIDS target of <5% for eradication of paediatric HIV within the context of a clinical study, but poor adherence to cART and follow-up can limit the benefit. Continued breastfeeding can prevent the rise in infant mortality after six months seen in previous studies, which encouraged early COB.

Cognitive and language outcomes in HIV-uninfected infants exposed to combined antiretroviral therapy in utero and through extended breast-feeding.

OBJECTIVE: To determine whether there is a higher risk for cognitive or language delay among HIV-exposed uninfected (HEU) children exposed to cART (zidovudine/lamivudine/lopinavir/ritonavir) in utero and through 1 year of breast-feeding (World health Organization Option B+), compared with the control children born to HIV-uninfected mothers. DESIGN: This is a double cohort study from Lusaka, Zambia. METHODS: HEU (n = 97) and control (n = 103) children aged 15-36 months were assessed on their early nonverbal problem-solving and language skills using the standardized Capute Scales. A score of less than 85 on the Capute Full-Scale Developmental Quotient (FSDQ) was considered indicative of developmental delay and was the primary outcome of interest. RESULTS: An FSDQ of less than 85 was found in eight (8.3%) of HEU participants and 15 (14.6%) of controls. In univariate logistic regressions, lower income [odds ratio (OR) = 0.93, P = 0.02], older infant age (OR = 1.08, P = 0.03), lower birth weight (OR = 0.16, P < 0.001), and less maternal education (OR = 0.41, P = 0.047) were associated with the probability of FSDQ less than 85, whereas Group (control/HEU) was not (OR = 1.88, P = 0.16). In the multivariable analysis, only lower birth weight (OR = 0.15, P < 0.001) remained associated with FSDQ less than 85. CONCLUSIONS: Our study did not support the presence of an adverse effect on cognitive and language development with prolonged antepartum and postpartum cART e/xposure. Larger studies and studies of older HEU children will be required to confirm these reassuring findings.