Mother's CD4+ count moderates the risk associated with higher parity for late postnatal HIV-free survival of breastfed children: an individual patient data meta-analysis of randomized controlled trials.

Risk association studies of late postnatal outcomes for children breastfed by HIV-1 positive mothers have had inconsistent findings and have not explored interactions among risk factors. This study addresses these limitations through an individual patient data (IPD) meta-analysis of HIV-free survival outcomes of nine randomized controlled trials to prevent early mother-to-child transmission of HIV-1. The pooled sample consisted of 3,324 African children in resource-limited settings who survived to age 28 days and were at-risk of acquiring HIV through breast milk. Based on a proportional hazards mixed effects meta-analysis, the composite endpoint of HIV-1 infection and all-cause mortality was found to be significantly associated with maternal immune status (CD4(+) ≥350 cells/mm(3), HR 0.59 95% CI (0.39, 0.87)), infant preterm delivery (gestational age <37 weeks, 1.40 (1.03, 1.89)), infant oral candidiasis infection (1.87, (1.53, 2.29)), and occurrence of breast abnormality before breastfeeding cessation (2.56 (1.90, 3.46)). A significant interaction between mother's parity (any previous pregnancy) and CD4(+) count ≥350 (HR 0.63 (0.40, 0.99), P-value = 0.045) suggested that higher CD4(+) count offsets the risk associated with higher parity. Further research is needed to elucidate the moderating effect of immune status on the risk associated with high parity and adverse late postnatal outcomes for infants breastfed by HIV-infected mothers in the absence of antiretroviral treatment.