EDITORIAL REVIEWChildren who are HIV-exposed and uninfected: evidence for actionPrendergast, Andrew J.a,b; Evans, Ceria,b Author Information aZvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe bBlizard Institute, Queen Mary University of London, UK. Correspondence to Professor Andrew J. Prendergast, Centre for Genomics and Child Health, Blizard Institute, 4 Newark Street, London E1 2AT, UK. Tel: +44 207 882 2269; fax: +44 207 882 2195; e-mail: [email protected] Received 7 June, 2022 Revised 11 October, 2022 Accepted 17 October, 2022 AIDS 37(2):p 205-215, February 1, 2023. | DOI: 10.1097/QAD.0000000000003409 Buy Metrics Abstract Prior to widespread availability of antiretroviral therapy (ART) in sub-Saharan Africa, children who were HIV-exposed but uninfected (HEU) had increased mortality, morbidity and undernutrition compared with children who were HIV-unexposed. Scale-up of ART has led to impressive declines in vertical HIV transmission, but over 15 million children are now HEU, 90% of whom live in sub-Saharan Africa. There are ongoing health disparities among children who are HEU, with higher mortality, morbidity and stunting and modest impairments in early child development, which collectively hamper health and human capital in high prevalence countries. The underlying causes are multifactorial and include exposure to HIV, co-infections and a skewed antenatal inflammatory milieu, particularly if mothers start ART once they have advanced disease, as well as socioeconomic risk factors, which may cluster in HIV-affected households. Improving maternal health through early and sustained ART, ensuring optimal breastfeeding, and implementing evidence-based priority interventions for all children in areas of high HIV prevalence, will likely improve outcomes. A more comprehensive intervention package based on the Nurturing Care Framework may have particular benefits for children who are HEU, to close health gaps and ensure that the next generation of HIV-free children survive and thrive, and lead healthy and productive lives. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.