Vascular and inflammatory biomarkers linked to neurocognition in Ugandan youth with perinatal HIV on dolutegravir

OBJECTIVES: To examine associations of immune biomarkers with neurocognition among Ugandan Youth living with Perinatally acquired HIV (YPHIV) virally suppressed on dolutegravir (DTG) versus Youth Without HIV (YWoH). METHODS: In this cross-sectional study of 101 age- and sex-matched youth in Kampala, Uganda (49 YPHIV, 52 YWoH), neurocognition was assessed using NeuroScreen. Biomarkers were measured using LEGENDplex™ and ELISA. Group differences were assessed using Wilcoxon rank-sum tests. Associations were evaluated using Spearman correlations and multivariable linear regression. RESULTS: Median age was 16.9 years [IQR 15.1-17.1]. YPHIV performed worse across all neurocognitive domains (P ≤ 0.035). IFAB, MIP-3α, and RANTES were higher among YPHIV (P ≤ 0.024). In adjusted YPHIV models, myeloperoxidase was associated with worse processing speed (β = -3.24, 95% CI = -4.89, -1.58), learning and memory (β = -3.53, 95% CI = -6.48, -0.59), and global z-scores (β = -1.64, 95% CI = -2.78, -0.51); soluble CD14 (sCD14) with worse processing speed (β = -0.78, 95% CI = -1.55, -0.01); β-d-Glucan (BDG) with worse learning and memory (β = -0.35, 95% CI = -0.68, -0.03). CONCLUSIONS: Ugandan YPHIV demonstrated worse neurocognitive performance. Biomarkers linked to HIV-related mortality and cardiovascular disease (MPO, sCD14, BDG) were associated with poorer performance.