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Clin Infect Dis. 2018 May 17;66(11):1668-1677. doi: 10.1093/cid/cix1102.

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.

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University of Bordeaux, Inserm, Bordeaux Population Health Research Center, Team IDLIC, France.
Department of Maternal, Newborn, Child and Adolescent Health, World Health Organization, Geneva, Switzerland.
Institut de recherche pour le développement UMI 174-PHPT, Marseille, France.
Faculty of Associated Medical Sciences, Chiang Mai University, Thailand.
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Department of International Health, Center for Global Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
Women's Health and Fertility Branch, Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention.
Emory University School of Medicine and Eastern Virginia Medical School, Atlanta, Georgia.
Division of Infectious Diseases, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill.
Sigma3 Services SÀRL, Nyon, Switzerland.
Maternal Adolescent and Child Health, University of the Witwatersrand, Johannesburg.
South African Medical Research Council, Cape Town.
Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
Gertrude H. Sergievsky Center, College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
Inserm, Centre de recherche Inserm U1027, Université Paul Sabatier Toulouse 3, France.
Center for Clinical Global Health Education, Johns Hopkins University, Baltimore, Maryland.
Makerere University-Johns Hopkins University Research Collaboration/MU-JHU CARE LTD, Kampala, Uganda.
Division of HIV, Infectious Diseases and Global Medicine, University of California San Francisco, and Zuckerberg San Francisco General Hospital.
University Paris-Diderot, Assitance Publique Hôpitaux de Paris.
Institut National d'Etudes Démographiques (Ined), Paris.
University of Bordeaux, Inserm, Bordeaux Population Health Research Center, Team Biostatistics, France.
Institute for Developmental Science and Global Health Research Institute, Faculty of Medicine, University of Southampton, United Kingdom.



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.


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.


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.


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.

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