part of 10.2217/fmb-2016-0055 © 2016 Future Medicine Ltd COMMENTARY Rethinking the HIV-exposed, uninfected child: epidemiologic perspectives Stanzi M le Roux* ,1,2 , Elaine J Abrams 3 & Landon Myer 1,2 1 Division of Epidemiology & Biostatistics, School of Public Health & Family Medicine, University of Cape Town, Anzio Road, Observatory 7925 Cape Town, South Africa 2 Centre for Infectious Diseases Epidemiology & Research, School of Public Health & Family Medicine, University of Cape Town, South Africa 3 ICAP, Columbia University Mailman School of Public Health, 10032 NY, USA *Author for correspondence: stanzi.leroux@uct.ac.za KEYWORDS • antiretroviral • child health • HIV exposed • HIV uninfected • maternal health Globally, more than 1 million HIV- exposed but uninfected (HEU) children were born in 2014 [1] . The number of HEU children born annually continues to rise, the predictable result of an ongoing adult HIV epidemic alongside new and effective strategies to prevent mother to child trans- mission (PMTCT) of HIV [1] . Since 2013, the WHO has recommended life-long uni- versal triple antiretroviral therapy (ART) for HIV-infected pregnant and breastfeed- ing women (‘Option B+’), with a strong emphasis on exclusive and extended breast- feeding in most resource-limited settings including sub-Saharan Africa (SSA) [2] . Historically, breastfeeding by HIV- infected women was discouraged in PMTCT programs globally, includ- ing those in most resource-limited set- tings [3] . At the same time, access to ART was sharply limited, largely to those with advanced HIV disease. In this context, a substantial body of evidence accumulated over time and across countries demonstrat- ing that HEU children were at increased risk of childhood mortality and morbidity. For example, a 2009 review encapsulated this thinking in providing an overview of these vulnerabilities [4] , drawing on pub- lications reporting HEU children to be at higher-than-expected risk of death, hospi- talization and infectious diseases including pneumonia and diarrhea [4,5] . Similarly, a range of immunological abnormalities have been reported among HEU children born during this time, including altered cytokine profiles, changes in lymphocyte subsets and low levels of protective maternal IgG antibodies in early infancy [4,6] . Why should we rethink the HIV-exposed, uninfected child? HEU children born under previous PMTCT strategies differed substantially from the ‘average,’ healthy, HIV-unexposed (HU) child by more than in utero exposure First draft submitted: 15 March 2016; Accepted for publication: 16 March 2016; Published online: 25 May 2016 “The number of HIV-exposed but uninfected children born annually continues to rise, the predictable result of an ongoing adult HIV epidemic alongside new and effective strategies to prevent mother to child transmission of HIV. ” Future Microbiol. (Epub ahead of print) ISSN 1746-0913 For reprint orders, please contact: reprints@futuremedicine.com