African Multi-Site Two-Year Longitudinal Study of Neurocognition in HIV Infected/Affected Children

Background: We compared cognitive outcomes at weeks 0, 48, and 96 for HIV-infected (HIV+), HIV-exposed uninfected (HEU), and HIV-unexposed (HUU) cohorts of children at 6 sub-Saharan sites. Methods: IMPAACT P1060 compared Nevirapine (NVP) versus Lopinavir/Ritonavir (LPV/r)-based ARV in children (HIV+) 6 to 35 months of age, were later enrolled for neurocognitive follow-up at 5 to 11 yrs of age. 611 (246 HIV+, 183 HEU, 182 HUU) of the 615 enrolled at 6 sites (South Africa [3], Zimbabwe, Malawi, Uganda), were compared across 3 assessment time points (weeks 0, 48, 96). 603 children completed week 48 and 588 completed week 96 visits. They were tested with the Kaufman Assessment Battery for Children, 2nd ed. (KABC-II) cognitive ability, Tests of Variables of Attention (TOVA) attention/impulsivity, Bruininks-Oseretsky Test of Motor Proficiency (BOT-2), and parental Behavior Rating Inventory of Executive Function (BRIEF). Cohorts were compared using linear mixed models adjusted for site, child's age and gender. Findings: Comparisons among cohorts were consistent across time points for most outcomes, with the HIV cohort significantly worse than the HEU and HUU cohorts for all KABC-II, TOVA, BOT-2 global outcomes (p<0·001). The HUU and HEU cohorts were comparable. For the KABC-II planning/reasoning subtests HIV+ children showed less improvement over time than the HUU/HEU groups, but showed improvement in other cognitive domains. Interpretation: Despite excellent clinical care and robust virological suppression from early childhood, the HIV+ group had poorer neurocognitive function longitudinally, especially for executive function. The neurocognitive deficits generally, but especially in planning/reasoning pose a serious risk as these children age into adolescence. Funding Statement: National Institutes of Health (NIH) National Institute of Allergic and Infectious Diseases (NIAID), National Institute of Mental Health (NIMH), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Declaration of Interests: All study authors declare no competing interests. Ethics Approval Statement: The institutional review board (IRB) approval for this study was obtained from the human subjects’ protection in research regulatory committee (Institutional Review Board or IRB) at each study site, and where applicable, the corresponding ministry of health in the host country, and the university partner in the United States for each study site. Informed consent was obtained from parents or primary caregivers with additional assent from children >7 years based on country regulations.