A meta-analysis assessing all-cause mortality in HIV-exposed uninfected compared to HIV-unexposed uninfected infants and children

OBJECTIVE: Conduct a meta-analysis examining differential all-cause mortality rates between HIV-exposed uninfected infants and children as compared to their HIV-unexposed uninfected counterparts. DESIGN: Meta-analysis summarizing the difference in mortality between HIV-exposed uninfected and HIV-unexposed uninfected infants and children. Reviewed studies comparing children in the two groups for all-cause mortality, in any setting, from 1994-2016 from six databases. METHODS: Meta-analyses were done estimating overall mortality comparing the two groups, stratified by duration of follow-up time from birth(0-12, 12-24 and > 24 months) and by year enrollment ended in each study: < 2002 compared to >/= 2002, when single-dose nevirapine for prevention of mother-to-child(PMTCT) commenced in low- and middle-income countries. RESULTS: Included 22 studies, for a total of 29,212 subjects (n = 8,840 (30.3%) HIV-exposed uninfected; n = 20,372 (37.7%) HIV-unexposed uninfected). Random effects models showed HIV-exposed uninfected had a > 70% increased risk of mortality vs. HIV-unexposed uninfected. Stratifying by age showed that HIV-exposed uninfected vs. HIV-unexposed uninfected had a significant 60-70% increased risk of death at every age strata. There was a significant 70% increase in the risk of mortality between groups prior to the implementation of PMTCT, which remained after 2002 (RR:1.46; 95%CI:1.14-1.87), when the availability of PMTCT services were widespread, suggesting that prenatal antiretroviral therapy, and healthier mothers, does not fully eliminate this increased risk in mortality. CONCLUSION: We show a consistent increase risk of mortality for HIV-exposed uninfected vs. HIV-unexposed uninfected infants and children. Longitudinal research is needed to elucidate underlying mechanisms, such as maternal and infant health status and breast feeding practices, which may help explain these differences in mortality.

• Epidemiology and Determinants of Health
  • Epidemiology
• Population(s)
  • Children or Youth (less than 18 years old)
• Prevention
  • Biomedical interventions