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

Shino Arikawa, Nigel Rollins, Gonzague Jourdain, Jean Humphrey, Athena P. Kourtis, Irving Hoffman, Max Essex, Tim Farley, Hoosen M. Coovadia, Glenda Gray, Louise Kuhn, Roger Shapiro, Valériane Leroy, Robert C. Bollinger, Carolyne Onyango-Makumbi, Shahin Lockman, Carina Marquez, Tanya Doherty, François Dabis, Laurent MandelbrotSophie Le Coeur, Matthieu Rolland, Pierre Joly, Marie Louise Newell, Renaud Becquet

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1668-1677
Number of pages10
JournalClinical Infectious Diseases
Volume66
Issue number11
DOIs
StatePublished - May 17 2018

Keywords

  • Africa
  • Asia
  • HIV-exposed uninfected
  • children
  • infants
  • mortality

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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    Arikawa, S., Rollins, N., Jourdain, G., Humphrey, J., Kourtis, A. P., Hoffman, I., Essex, M., Farley, T., Coovadia, H. M., Gray, G., Kuhn, L., Shapiro, R., Leroy, V., Bollinger, R. C., Onyango-Makumbi, C., Lockman, S., Marquez, C., Doherty, T., Dabis, F., ... Becquet, R. (2018). 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. Clinical Infectious Diseases, 66(11), 1668-1677. https://doi.org/10.1093/cid/cix1102