Contribution of Maternal Antiretroviral Therapy and Breastfeeding to 24-Month Survival in Human Immunodeficiency Virus-Exposed Uninfected Children: An Individual Pooled Analysis of African and Asian Studies

• Authors: Shino Arikawa, Universite de Bordeaux; Nigel Rollins, Organisation Mondiale de la Sante; Gonzague Jourdain, Institut de Recherche pour le Développement (IRD) UMI 174-PHPT; Jean Humphrey, Johns Hopkins Bloomberg School of Public Health; Athena P. Kourtis, Emory University; Irving Hoffman, University of North Carolina School of Medicine; Max Essex, Harvard School of Public Health; Tim Farley, Sigma 3 Services SÀRL; Hoosen M. Coovadia, University of Witwatersrand; Glenda Gray, South African Medical Research Council; Louise Kuhn, Gertrude H. Sergievsky Center; Roger Shapiro, Harvard School of Public Health; Valeriane Leroy, Universite Paul Sabatier Toulouse III; Robert C. Bollinger, Johns Hopkins University; Carolyne Onyango-Makumbi, Makerere University; Shahin Lockman, Harvard School of Public Health; Carina Marquez, University of California San Francisco; Tanya Doherty, South African Medical Research Council; Francois Dabis, Universite de Bordeaux; Laurent Mandelbrot, University Paris-Diderot; Sophie Le Coeur, Institut de Recherche pour le Développement (IRD) UMI 174-PHPT; Matthieu Rolland, Universite de Bordeaux; Pierre Joly, Inserm; Marie-Louise Newell, University of Southampton; Renaud Becquet, Universite de Bordeaux
• Journal Title: Clinical Infectious Diseases
• Volume: Volume 66, Number 11
• Publisher: Oxford University Press (OUP): Policy B - Oxford Open Option C | 2018-05-17, Pages 1668-1677
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1093/cid/cix1102
• Subjects: Health Sciences, Medicine and Surgery; Health Sciences, Public Health
• Keywords: HIV-exposed uninfected; children; infants; mortality; Africa; Asia

Abstract

Background Human immunodeficiency virus (HIV)-infected pregnant women increasingly receive antiretroviral therapy (ART) to prevent mother-to-child transmission (PMTCT). Studies suggest HIV-exposed uninfected (HEU) children face higher mortality than HIV-unexposed children, but most evidence relates to the pre-ART era, breastfeeding of limited duration, and considerable maternal mortality. Maternal ART and prolonged breastfeeding while on 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 from 1995 to 2015 in Africa and Asia were pooled to estimate the association between 24-month mortality and maternal/infant factors, using random-effects Cox proportional hazards models. Adjusted attributable fractions of risks computed using the predict function in the R package "frailtypack" were used to estimate the relative contribution of risk factors to overall mortality. Results Cumulative incidence of death was 5.5% (95% confidence interval, 5.1-5.9) by age 24 months. Low birth weight (LBW <2500 g, 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 the population level, LBW accounted for 16.2% of 24-month mortality, never breastfeeding for 10.8%, mother not receiving ART for 45.6%, and maternal death for 4.3%; combined, these factors explained 63.6% of deaths by age 24 months. Conclusions Survival of HEU children could be substantially improved if public health practices provided all HIV-infected mothers with ART and supported optimal infant feeding and care for LBW neonates.