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The objective of this study was to systematically review the clinical and preclinical literature on the effects of <jats:italic>in utero<\/jats:italic> exposure to <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> and\/or antiretroviral therapy (<jats:styled-content style=\"fixed-case\">ART<\/jats:styled-content>) on neurodevelopment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We systematically searched <jats:styled-content style=\"fixed-case\">OVID<\/jats:styled-content> Medline, Psyc<jats:styled-content style=\"fixed-case\">INFO<\/jats:styled-content> and Embase, as well as the Cochrane Collaborative Database, Google Scholar and bibliographies of pertinent articles. Titles, abstracts, and full texts were assessed independently by two reviewers. Data from included studies were extracted. Results are summarized qualitatively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The search yielded 3027 unique titles. Of the 255 critically reviewed full\u2010text articles, 25 met inclusion criteria for the systematic review. Five articles studied human subjects and looked at brain structure and function. The remaining 20 articles were preclinical studies that mostly focused on behavioural assessments in animal models. The few clinical studies had mixed results. Some clinical studies found no difference in white matter while others noted higher fractional anisotropy and lower mean diffusivity in the brains of <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010exposed uninfected children compared to <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010unexposed uninfected children, correlating with abnormal neurobehavioral scores. Preclinical studies focused primarily on neurobehavioral changes resulting from monotherapy with either zidovudine or lamivudine. Various developmental and behavioural changes were noted in preclinical studies with <jats:styled-content style=\"fixed-case\">ART<\/jats:styled-content> exposure, including decreased grooming, decreased attention, memory deficits and fewer behaviours associated with appropriate social interaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>While the existing literature suggests that there may be some neurobehavioral differences associated with <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ART<\/jats:styled-content> exposure, limited data are available to substantially support these claims. More research is needed comparing neurobiological factors between <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010exposed uninfected and <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010unexposed uninfected children and using exposures consistent with current clinical care.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jia2.25275","type":"journal-article","created":{"date-parts":[[2019,4,15]],"date-time":"2019-04-15T08:11:30Z","timestamp":1555315890000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["<i>In utero<\/i> exposure to <scp>HIV<\/scp> and\/or antiretroviral therapy: a systematic review of preclinical and clinical evidence of cognitive outcomes"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6753-0928","authenticated-orcid":false,"given":"Megan S","family":"McHenry","sequence":"first","affiliation":[{"name":"Department of Pediatrics Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Academic Model Providing Access to Healthcare (AMPATH) Eldoret Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayode A","family":"Balogun","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute University Health Network Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenna C","family":"McDonald","sequence":"additional","affiliation":[{"name":"Department of Radiology and Imaging Sciences Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5460-8204","authenticated-orcid":false,"given":"Rachel C","family":"Vreeman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Academic Model Providing Access to Healthcare (AMPATH) Eldoret Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth C","family":"Whipple","sequence":"additional","affiliation":[{"name":"Ruth Lilly Medical Library Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Serghides","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute University Health Network Toronto Canada"},{"name":"Department of Immunology Institute of Medical Sciences Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,15]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"UNICEF.Eliminating Mother\u2010to\u2010Child\u2010 Transmission: UNICEF Data: UNICEF;2016[cited 2018 Mar 19]. 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