Contribution of maternal ART and breastfeeding to 24-month survival in HIV-exposed uninfected children: an individual pooled analysis of African and Asian studies.

Background Increasing numbers of HIV-infected pregnant women receive antiretroviral therapy (ART) to prevent mother-to-child transmission (PMTCT). Studies suggested that HIV-exposed uninfected (HEU) children face higher mortality than HIV-unexposed children, but evidence mostly relates to the pre-ART era, breastfeeding of limited duration and considerable maternal mortality. Maternal ART and prolonged breastfeeding under cover of ART may improve survival, although this has not been reliably quantified. Methods Individual data on 19,219 HEU children from 21 PMTCT trials/cohorts undertaken 1995-2015 in Africa and Asia were pooled and the association between 24-month mortality and maternal/infant factors quantified using random-effects Cox proportional hazards models accounting for between-study heterogeneity. Adjusted attributable fractions of risks computed using the predict function in the R package "frailtypack" estimate the relative contribution of risk factors to overall mortality in HEU children. Results Cumulative incidence of death was 5.5% (95%CI: 5.1-5.9) by age 24 months. Low birth weight (LBW<2500g, adjusted Hazard Ratio (aHR: 2.9), no breastfeeding (aHR: 2.5) and maternal death (aHR: 11.1) were significantly associated with increased mortality. Maternal ART (aHR: 0.5) was significantly associated with lower mortality. At population level, LBW accounted for 16.2% of child deaths by 24 months, never breastfeeding for 10.8%, mother not receiving ART for 45.6%, and maternal death for 4.3%; these factors combined explained 63.6% of deaths by age 24 months. Conclusion Survival of HEU children could be substantially improved if public health strategies provided all mothers living with HIV with ART and supported optimal infant feeding and care for LBW neonates.