Newell, Marie-Louise, Rollins, N., Jourdain, Gonzague, Humphrey, Jean, Kourtis, Athena, Hoffman, Irving, Essex, Max, Farley, Tim, Coovadia, Hoosen, Gray, Glenda, Kuhn, Louise, Shapiro, Roger, Leroy, Valeriane, Bollinger, Robert, Onyago-Makumbi, Carolyne, Lockman, Shahin, Marquez, Carina, Doherty, Tanya, Dabis, Francois, Mandelbrot, Laurent, Le Coeur, Sophie, Rolland, Matthieu, Joly, Pierre and Becquet, Renaud (2018) Contribution of maternal ART and breastfeeding to 24-month survival in HIV-exposed uninfected children: an individual pooled analysis of African and Asian studies. Clinical Infectious Diseases, 66 (11), 1668-1677. (doi:10.1093/cid/cix1102).
Abstract
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.
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