Meta-analysis assessing all-cause mortality in HIV-exposed uninfected compared with HIV-unexposed uninfected infants and children

The study aimed to examine differential all-cause mortality rates between HIV-exposed uninfected (HEU) and HIV-unexposed uninfected (HUU) infants and children. The meta-analysis included 22 studies, comprising a total of 29,212 study participants. The studies compared children in the two groups for all-cause mortality in any setting from 1994 to 2016, sourced from six databases. The meta-analyses estimated overall mortality comparing the two groups, stratified by duration of follow-up time from birth and by year enrollment ended in each study. Random effects models showed that HEU had a more than 70% increased risk of mortality versus HUU. Stratifying by age revealed that HEU versus HUU had a significant 60-70% increased risk of death at every age strata. A significant 70% increase in the risk of mortality between groups was observed before the implementation of pre-exposure prophylaxis (PMTCT) services, which remained after 2002, when the availability of PMTCT services was widespread. The findings suggest that prenatal antiretroviral therapy and healthier mothers do not fully eliminate the increased risk of mortality in HEU infants and children. A consistent increase in risk of mortality for HEU versus HUU infants and children was observed. Longitudinal research is needed to elucidate underlying mechanisms, such as maternal and infant health status and breastfeeding practices, which may help explain these differences in mortality.