Vascular risk drives cognitive decline over 10 years in people aging with well controlled HIV

OBJECTIVE: To characterize long-term cognitive trajectories in adults aging with well controlled HIV and identify baseline predictors of cognitive decline. DESIGN: Prospective, multicenter longitudinal cohort study with repeated cognitive assessments for up to 10 years. METHODS: Positive Brain Health Now enrolled HIV+ adults aged ≥35 years without dementia and followed at 9-12-month intervals across two study phases (2013-2018; 2019-2024). Cognitive performance was assessed using the Brief Cognitive Ability Measure (B-CAM). Group-based trajectory modeling identified patterns of cognitive change among participants with at least one visit in each phase. Baseline predictors of declining trajectory membership were examined using generalized estimating equations. RESULTS: Two cognitive trajectories were identified: one stable and one declining. Although no decline was detected during the initial 3-year follow-up, 47% of participants exhibited decline over up to 10 years, with an estimated 0.35-0.5 SD difference in B-CAM scores between trajectories. The strongest baseline predictors of decline were higher cognitive performance (floor effect), higher Framingham Risk Score and peripheral artery disease [odds ratio (OR) [95% CI]: 2.84 [1.35-5.98] and 3.07 [2.06-4.57]], and older age, lower education, needing academic support, cannabis use, anxiety, low motivation, detectable plasma HIV RNA, and higher VACS Index 1.0 scores. Nadir CD4 + count and HIV duration were not independently associated with decline. CONCLUSIONS: Among adults aging with well controlled HIV, cognitive decline, when present, progressed slowly and was driven primarily by vascular risk factors, suggesting that, in the current treatment era, vascular comorbidities may play a greater role in cognitive decline than traditional HIV-related factors.