Immune activation is associated with neurocognitive performance in Ugandan Adolescents living with HIV.

We examined relationships between neurocognition and immune activation in Ugandan adolescents with perinatally acquired HIV (PHIV). Eighty-nine adolescents in Kampala, Uganda (32 virally suppressed [<400 copies/mL] PHIV and 57 socio-demographically matched HIV- controls) completed a tablet-based neurocognitive test battery. Control derived z-scores for 12 individual tests and a global/overall z-score were calculated. We measured plasma (soluble CD14 and CD163), monocyte (proportions of monocyte subsets), and T cell (expression of CD38 and HLA-DR on CD4+ and CD8+) activation and gut markers. Spearman's rank correlations and median regressions examined associations between test performance and immune activation. Median [IQR] age was 15[13-16] years, 40% were females. Median time on ART was 10 years [7-11] for PHIV; 87% had viral load <50 copies/mL. Compared to controls, global z-scores were lower among PHIV (p=0.05), and significantly worse on tests of executive functioning and delayed recall (p's≤0.05). Overall, monocyte activation significantly correlated with worse test performance on global z-score (r=0.21, p=0.04), attention, processing speed, and motor speed (r=0.2-0.3, p≤0.01). T cell activation was significantly correlated with worse performance on tests of learning, executive functioning, and working memory (r=0.2-0.4, p≤0.04). In PHIV, after adjusting for age, sex, and ART duration, activated CD4 T cells remained associated with worse memory (β-0.3, 95% CI, -0.55, -.07, p=0.01). PHIV with virologic suppression on ART show evidence of worse neurocognitive test performance compared to controls. Monocyte and T cell activation is correlated with worse neurocognition in Ugandan youth with and without HIV which has not been previously investigated in this setting.