Mortality risk and associated factors in HIV-exposed, uninfected children

With increasing maternal antiretroviral treatment (ART), the number of children newly infected with HIV has declined. However, the possible increased mortality in the large number of HIV-exposed, uninfected (HEU) children may be of concern. We quantified mortality risks among HEU children and reviewed associated factors.

Systematic search of electronic databases (PubMed, Scopus). We included all studies reporting mortality of HEU children to age 60 months and associated factors. Relative risk of mortality between HEU and HIV-unexposed, uninfected (HUU) children was extracted where relevant. Inverse variance methods were used to adjust for study size. Random-effects models were fitted to obtain pooled estimates.

A total of 14 studies were included in the meta-analysis and 13 in the review of associated factors. The pooled cumulative mortality in HEU children was 5.5% (95% CI: 4.0-7.2; I(2) = 94%) at 12 months (11 studies) and 11.0% (95% CI: 7.6-15.0; I(2) = 93%) at 24 months (four studies). The pooled risk ratios for the mortality in HEU children compared to HUU children in the same setting were 1.9 (95% CI: 0.9-3.8; I(2) = 93%) at 12 months (four studies) and 2.4 (95% CI: 1.1-5.1; I(2) = 93%) at 24 months (three studies).

Compared to HUU children, mortality risk in HEU children was about double at both age points, although the association was not statistically significant at 12 months. Interpretation of the pooled estimates is confounded by considerable heterogeneity between studies. Further research is needed to characterise the impact of maternal death and breastfeeding on the survival of HEU infants in the context of maternal ART, where current evidence is limited.