Objective:To describe longitudinal outcomes and predictors of cognitive outcomes in children with HIV in Zambia.Background:Multiple studies have shown that children with HIV are at risk for impaired cognition. However, there are limited data on longitudinal cognitive outcomes in children with HIV.Methods:We conducted a prospective cohort study of 208 perinatally infected children with HIV ages 8-17 years, all treated with antiretroviral therapy, and 208 HIV-exposed uninfected controls. Participants were followed for 2 years. Cognition was assessed with a custom NIH Toolbox Cognition Battery, and tests were combined to generate a Summary Cognition Score (SCS). The contribution of potential risk factors to outcomes was explored using regression models and group-based trajectory modeling.Results:HIV was strongly associated with lower SCS at baseline [β-14, 95% confidence interval (CI): -20 to -7, P < 0.001]. Change scores over time were similar between groups, but poorer average performance in children with HIV persisted at the 2-year follow-up visit (adjusted β = -11, 95% CI: -22 to -0.3, P = 0.04). Other than HIV, the strongest predictors of baseline SCS included socioeconomic status index (β =3, 95% CI: 1, 5, P = 0.004), history of growth stunting (β=-14, 95% CI: -23 to -6, P = 0.001), history of CD4 count below 200 (β = -19, 95% CI: -35 to -2, P = 0.02), and history of World Health Organization stage 4 disease (β = -10, 95% CI: -19 to -0.2, P = 0.04). In the group-based trajectory model, HIV+ status predicted membership in the lowest performing trajectory group (odds ratio 2.5, 95% CI: 1.2 to 5.1, P = 0.01).Conclusions:Children with HIV are at risk of poor cognitive outcomes, despite chronic treatment with antiretroviral therapy.
