Health and survival of HIV perinatally exposed but uninfected children born to HIV-infected mothers.

Abstract

The number of HIV-exposed but uninfected (HEU) infants exposed to both HIV and multiple antiretroviral drugs in utero and during prolonged breastfeeding is increasing in low-income countries where HIV prevalence is the highest. We review recent evidence on the effects of perinatal/postnatal exposure to maternal HIV and combined antiretroviral therapy (cART) on health outcomes of HEU children (mitochondrial and metabolic toxicity, adverse pregnancy outcomes, neurodevelopment, growth, infectious morbidity, and mortality). Several studies have reported ART-associated mitochondrial toxicity and metabolic disorders with conflicting results on adverse pregnancy outcomes, underscoring the need to conduct further investigations on these questions. Studies about congenital abnormalities report no significant differences between HEU exposed to ART and HIV-unexposed (HUU) children. Updated French data showed no significant difference in cancer incidence between HEU cART-exposed children and the general paediatric population. Furthermore, HEU children exposed to maternal cART have modest but significant impairment of development and a higher risk of growth impairment. Finally, HEU have higher risks of infections (mainly low respiratory tract infections and diarrhoea) and malaria than HUU children, particularly in children not breastfed or after early weaning. Higher mortality risk from infectious disease is reported in HEU compared to HUU children. As we move toward the elimination of mother-to-child transmission of HIV, HEU children are an emerging population whose health outcomes remain to be fully described. Future large cohorts of HEU children using careful comparison groups of HUU in the post-ART era are needed to better understand their long-term health outcomes.