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 HIVuninfected
children aged ≤10 years, by maternal HIV status. Studies were appraised by NewcastleOttawa
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.