PMID- 34259393 OWN - NLM STAT- MEDLINE DCOM- 20211025 LR - 20240402 IS - 1758-2652 (Electronic) IS - 1758-2652 (Linking) VI - 24 IP - 7 DP - 2021 Jul TI - Cognitive outcomes at ages seven and nine years in South African children from the children with HIV early antiretroviral (CHER) trial: a longitudinal investigation. PG - e25734 LID - 10.1002/jia2.25734 [doi] LID - e25734 AB - INTRODUCTION: Many children living with HIV (CLWH) display impaired cognition. Although early combination antiretroviral therapy (ART) produces improved cognitive outcomes, more long-term 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-Def; n = 22); immediate time-limited ART for 40 weeks (ART-40W; n = 30) and immediate time-limited ART for 96 weeks (ART-96W; n = 18). We also recruited HIV-exposed uninfected (CHEU; n = 28) and HIV-unexposed (CHU; n = 35) children. METHODS: Data were collected between May 2012 and December 2017. Mixed-model repeated-measures ANOVAs assessed differences over time between CLWH (ART-40W, ART-96W and ART-Def) and CHIV- CHEU and CHU between ART-Early (ART-40W and ART-96W), ART-Def, CHEU and CHU; and between ART-40W, ART-96W, ART-Def, CHEU and CHU. RESULTS: All comparisons found significant effects of Time for most outcome variables (better scores at nine than at seven years; ps < 0.05). The first ANOVAs found that for (a) motor dexterity, CLWH performed worse than CHIV- at seven years (p < 0.001) but improved to equivalence at nine years, (b) visual-spatial processing and problem solving, only CLWH (p < 0.04) showed significant performance improvement over time and (c) working memory and executive function, CLWH performed worse than CHIV- at both seven and nine years (p = 0.03 and 0.04). The second ANOVAs found that for (a) working memory, CHU performed better than ART-Early and CHEU (p < 0.01 and <0.04), and (b) motor dexterity, ART-Def performed worse than ART-Early, CHEU and CHU at seven years (p = 0.02, <0.001 and <0.001 respectively) but improved to equivalence at nine years (ps > 0.17). Similarly, for motor dexterity, ART-Def performed worse than ART-96W, CHEU and CHU at seven years (p < 0.04, <0.001 and <0.001) but improved to equivalence at nine years (ps > 0.20). CONCLUSIONS: Although neurocognitive developmental trajectories for treatment groups and controls were largely similar (i.e. performance improvements from 7 to 9), all ART-treated 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's future learning, reasoning and adaptive functioning. CI - (c) 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society. FAU - van Wyhe, Kaylee S AU - van Wyhe KS AUID- ORCID: 0000-0002-0123-0540 AD - ACSENT Laboratory, Department of Psychology, University of Cape Town, Cape Town, South Africa. AD - Family Centre for Research with Ubuntu, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences Stellenbosch University, Cape Town, South Africa. FAU - Laughton, Barbara AU - Laughton B AUID- ORCID: 0000-0001-7260-7723 AD - Family Centre for Research with Ubuntu, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences Stellenbosch University, Cape Town, South Africa. FAU - Cotton, Mark F AU - Cotton MF AUID- ORCID: 0000-0003-2559-6034 AD - Family Centre for Research with Ubuntu, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences Stellenbosch University, Cape Town, South Africa. FAU - Meintjes, Ernesta M AU - Meintjes EM AD - Biomedical Engineering Research Centre, Division of Biomedical Engineering, Department of Human Biology, University of Cape Town, South Africa. FAU - van der Kouwe, Andre Jw AU - van der Kouwe AJ AD - Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA. FAU - Boivin, Michael J AU - Boivin MJ AD - Department of Psychiatry and Neurology and Ophthalmology, Michigan State University, East Lansing, MI, USA. AD - Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA. FAU - Kidd, Martin AU - Kidd M AD - Centre of Statistical Consultation, Stellenbosch University, Cape Town, South Africa. FAU - Thomas, Kevin Gf AU - Thomas KG AD - ACSENT Laboratory, Department of Psychology, University of Cape Town, Cape Town, South Africa. LA - eng GR - R01 DC015984/DC/NIDCD NIH HHS/United States GR - R01 HD071664/HD/NICHD NIH HHS/United States GR - R01 HD099846/HD/NICHD NIH HHS/United States GR - U19 AI053217/AI/NIAID NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - Switzerland TA - J Int AIDS Soc JT - Journal of the International AIDS Society JID - 101478566 RN - 0 (Anti-Retroviral Agents) SB - IM MH - Anti-Retroviral Agents/therapeutic use MH - Black People MH - Child MH - Cognition MH - *Cognitive Dysfunction MH - *HIV Infections/drug therapy MH - Humans PMC - PMC8278859 OTO - NOTNLM OT - HIV-associated neurocognitive impairment OT - HIV/AIDS OT - The Children with HIV Early Antiretroviral Therapy (CHER) trial OT - antiretroviral therapy OT - paediatric HIV OT - working memory EDAT- 2021/07/15 06:00 MHDA- 2021/10/26 06:00 PMCR- 2021/07/14 CRDT- 2021/07/14 08:57 PHST- 2021/04/13 00:00 [revised] PHST- 2020/12/04 00:00 [received] PHST- 2021/04/22 00:00 [accepted] PHST- 2021/07/14 08:57 [entrez] PHST- 2021/07/15 06:00 [pubmed] PHST- 2021/10/26 06:00 [medline] PHST- 2021/07/14 00:00 [pmc-release] AID - JIA225734 [pii] AID - 10.1002/jia2.25734 [doi] PST - ppublish SO - J Int AIDS Soc. 2021 Jul;24(7):e25734. doi: 10.1002/jia2.25734.