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

ObjectiveHIV-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. MethodsWe 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. ResultsWe 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. ConclusionsThe 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.