Clinical outcomes of HIV-exposed, HIV-uninfected children in sub-Saharan Africa.

OBJECTIVE: HIV-exposed but HIV-uninfected (HEU) children are widely considered at increased risk of mortality and morbidity. Recent advances in prevention of mother-to-child HIV transmission (PMTCT) strategies, incorporating life-long universal maternal antiretroviral therapy (ART, "Option B+") with extended breastfeeding, may improve HEU child health substantially. We critically reviewed reports of mortality/morbidity among HEU and HIV-unexposed (HU) children in sub-Saharan Africa.

METHODS: We searched Medline, EMBASE, CINAHL, PsycINFO, Academic Search Premier, Global Health & Psychosocial Instruments databases, conference abstracts, and reference lists for longitudinal studies from sub-Saharan Africa reporting mortality and clinical morbidity among HIV-uninfected children aged ≤10 years, by maternal HIV status. Studies were appraised by Newcastle-Ottawa Scale and ACROBAT-NRSI. Due to substantial heterogeneity of study designs, populations and results (I(2) = 75%), data were not synthesised.

RESULTS: We included 37 reports (28 studies, 11 164 HEU children); methodological and reporting quality were variable. Most reports came from settings without universal access to maternal ART (n = 35). Results were conflicting, with some studies indicating increased risk of mortality, hospitalisation and/or under-nutrition among HEU children, while others found no evidence of increased risk. In subanalyses, improved maternal health, ART use and breastfeeding were strongly protective for all outcomes. Only 39% (11/28) of studies adjusted for major confounders. Reports from settings using universal maternal ART with breastfeeding (n = 2) found no differences in growth or development but did not report mortality or infectious morbidity.

CONCLUSIONS: The existing literature provides little insight into HEU child health under recently adopted PMTCT strategies. There is a need for robust comparative data on HEU and HIV-unexposed child health outcomes under Option B+; optimising breastfeeding practices and increasing maternal use of ART should be urgent public health priorities.