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Although early combination antiretroviral therapy (ART) produces improved cognitive outcomes, more long\u2010term outcome data are needed. After concluding the Children with HIV Early antiRetroviral (CHER) trial in 2011, we investigated cognitive performance, at seven and nine years of age. Participants had been randomized to deferred ART (ART\u2010Def; n\u00a0=\u00a022); immediate time\u2010limited ART for 40\u00a0weeks (ART\u201040W; n\u00a0=\u00a030) and immediate time\u2010limited ART for 96\u00a0weeks (ART\u201096W; n\u00a0=\u00a018). We also recruited HIV\u2010exposed uninfected (CHEU; n\u00a0=\u00a028) and HIV\u2010unexposed (CHU; n\u00a0=\u00a035) children.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data were collected between May 2012 and December 2017. Mixed\u2010model repeated\u2010measures ANOVAs assessed differences over time between CLWH (ART\u201040W, ART\u201096W and ART\u2010Def) and CHIV\u2010 CHEU and CHU between ART\u2010Early (ART\u201040W and ART\u201096W), ART\u2010Def, CHEU and CHU; and between ART\u201040W, ART\u201096W, ART\u2010Def, CHEU and CHU.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All comparisons found significant effects of Time for most outcome variables (better scores at nine than at seven years; <jats:italic>p<\/jats:italic>s\u00a0&lt;\u00a00.05). The first ANOVAs found that for (a) motor dexterity, CLWH performed worse than CHIV\u2010 at seven years (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001) but improved to equivalence at nine years, (b) visual\u2010spatial processing and problem solving, only CLWH (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.04) showed significant performance improvement over time and (c) working memory and executive function, CLWH performed worse than CHIV\u2010 at both seven and nine years (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.03 and 0.04). The second ANOVAs found that for (a) working memory, CHU performed better than ART\u2010Early and CHEU (<jats:italic>p\u00a0<\/jats:italic>&lt;\u00a00.01 and &lt;0.04), and (b) motor dexterity, ART\u2010Def performed worse than ART\u2010Early, CHEU and CHU at seven years (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.02, &lt;0.001 and &lt;0.001 respectively) but improved to equivalence at nine years (<jats:italic>p<\/jats:italic>s\u00a0&gt;\u00a00.17). Similarly, for motor dexterity, ART\u2010Def performed worse than ART\u201096W, CHEU and CHU at seven years (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.04, &lt;0.001 and &lt;0.001) but improved to equivalence at nine years (<jats:italic>p<\/jats:italic>s\u00a0&gt;\u00a00.20).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although neurocognitive developmental trajectories for treatment groups and controls were largely similar (i.e. performance improvements from 7 to 9), all ART\u2010treated children, regardless of treatment arm, remain at risk for cognitive deficits over early school ages. Although the nature of these deficits may change as cognitive development proceeds, there are potential negative consequences for these children\u2019s future learning, reasoning and adaptive functioning.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jia2.25734","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T12:10:30Z","timestamp":1626264630000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Cognitive outcomes at ages seven and nine years in South African children from the children with HIV early antiretroviral (CHER) trial: a longitudinal investigation"],"prefix":"10.1002","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0123-0540","authenticated-orcid":false,"given":"Kaylee S","family":"van Wyhe","sequence":"first","affiliation":[{"name":"ACSENT Laboratory Department of Psychology University of Cape Town Cape Town South Africa"},{"name":"Family Centre for Research with Ubuntu Department of Paediatrics and Child Health Faculty of Medicine and Health Sciences Stellenbosch University Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7260-7723","authenticated-orcid":false,"given":"Barbara","family":"Laughton","sequence":"additional","affiliation":[{"name":"Family Centre for Research with Ubuntu Department of Paediatrics and Child Health Faculty of Medicine and Health Sciences Stellenbosch University Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2559-6034","authenticated-orcid":false,"given":"Mark F","family":"Cotton","sequence":"additional","affiliation":[{"name":"Family Centre for Research with Ubuntu Department of Paediatrics and Child Health Faculty of Medicine and Health Sciences Stellenbosch University Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernesta M","family":"Meintjes","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Research Centre Division of Biomedical Engineering Department of Human Biology University of Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andre JW","family":"van der Kouwe","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging Massachusetts General Hospital Charlestown MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J","family":"Boivin","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurology and Ophthalmology Michigan State University East Lansing MI USA"},{"name":"Department of Psychiatry University of Michigan Ann Arbor MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Kidd","sequence":"additional","affiliation":[{"name":"Centre of Statistical Consultation Stellenbosch University Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin GF","family":"Thomas","sequence":"additional","affiliation":[{"name":"ACSENT Laboratory Department of Psychology University of Cape Town Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,7,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000001683"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/cch.12321"},{"issue":"4","key":"e_1_2_9_4_1","first-page":"156","article-title":"Neurological complications of HIV\/AIDS in childhood","volume":"29","author":"Donald KAM","year":"2011","journal-title":"Continuing Med Educ"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A4921"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000000766"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2431-12-95"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/500412"},{"key":"e_1_2_9_9_1","first-page":"1","volume-title":"Neurodevelopmental delay in pediatric HIV\/AIDS: current perspectives","author":"Blokhuis C","year":"2016"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0800971"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61409-9"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.4102\/sajhivmed.v15i3.7"},{"issue":"2","key":"e_1_2_9_13_1","first-page":"39","article-title":"The motor development of 2 to 6\u2010year old children infected with HIV","volume":"30","author":"Botha J\u2010AE","year":"2008","journal-title":"S Afr J Res Sport Physical Educ Recreation"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328355d0ce"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2989\/17280580409486573"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jia2.25106"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(12)70242-6"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e31827fb19d"},{"issue":"3","key":"e_1_2_9_19_1","first-page":"186","article-title":"A preliminary examination of the construct validity of the KABC\u2010II in Ugandan children with a history of cerebral malaria","volume":"9","author":"Bangirana P","year":"2009","journal-title":"Afr Health Sci"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2011.01517.x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.7448\/IAS.20.1.21412"},{"issue":"3","key":"e_1_2_9_22_1","first-page":"108","article-title":"Neurological and cognitive function of HIV\u2010infected children commenced on antiretroviral therapy","volume":"2","author":"Eley BS","year":"2008","journal-title":"S Afr J Child Health"},{"key":"e_1_2_9_23_1","volume-title":"Purdue pegboard test","author":"Tiffen J","year":"1968"},{"key":"e_1_2_9_24_1","volume-title":"The Beery\u2010Buktenica developmental test of visual\u2010motor integration: administration, scoring, and teaching manual","author":"Beery KEBNA","year":"2010"},{"key":"e_1_2_9_25_1","volume-title":"A compendium of neuropsychological tests: Administration, norms, and commentary","author":"Strauss ESEMS","year":"2006"},{"key":"e_1_2_9_26_1","volume-title":"Kaufman assessment battery for children: second edition (KABC\u2010II)","author":"Kaufman AS","year":"2004"},{"key":"e_1_2_9_27_1","unstructured":"LearkRA GreenbergLM KindschiCL DupuyTR HughesSJA.A. \u00ae professional manual test of variables of attention continuous performance test.2007."},{"key":"e_1_2_9_28_1","volume-title":"PPVT\u20104: Peabody picture vocabulary test","author":"Dunn LMDDM","year":"2007"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.281053"},{"key":"e_1_2_9_30_1","unstructured":"Department of Education.Age requirements for admission to an ordinary public school[cited 2021 Mar 17]. 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