BackgroundMedication adherence is a critical issue in achieving viral suppression targets, particularly in resource-limited countries. As HIV-related cognitive impairment (CI) impacts adherence, we examined frequency and predictors of CI in the African Cohort Study.SettingCross-sectional examination of enrollment data from President's Emergency Plan for AIDS Relief supported clinic sites.MethodsIn a 30-minute cognitive assessment, CI was defined as -1SD on 2 tests or -2SD on one, as compared with 429 controls. We performed univariable and multivariable logistic and linear models examining clinical and demographic factors associated with CI and global neuropsychological performance (NP-6).ResultsTwo thousand four hundred seventy-two HIV+ participants from Kenya (n = 1503), Tanzania (n = 469), and Uganda (n = 500). The mean (SD) age was 39.7 (10.7) years, and 1452 (59%) were women. The majority reported completing or partially completing primary school (n = 1584, 64%). Mean (SD) current and nadir CD4 count were 463 (249) and 204 (221) cells/mm, respectively; 1689 (68%) were on combination antiretroviral therapy. Nine hundred thirty-nine (38%) HIV+ versus 113 (26%) HIV- individuals showed CI: (P < 0.001). We found significant effects of literacy [odds ratio (OR): 0.3; 95% CI: 0.2 to 0.4; P < 0.001] and World Health Organization stage 4 (OR: 1.5; 95% CI: 1.0 to 2.q; P = 0.046) on CI. Tanzanians (OR: 3.2; 95% CI: 2.4 to 4.3; P < 0.001) and Kenyans (OR: 2.0; 95% CI: 1.6 to 2.6; P < 0.001) had higher risk of CI compared with Ugandans. Results were relatively unchanged in predictive models of NP-6, with the only difference being an additional significant effect of current CD4 cell count (coeff: 0.0; 95% CI: 0.0 to 0.0; P = 0.005).ConclusionsLiteracy, country, World Health Organization stage, and current CD4 cell count were associated with increased risk of cognitive dysfunction. Our findings help optimize care practices in Africa, illustrating the importance of strategies for early and effective viral-immunological control