Abstract Background As persons with HIV (PWH) live longer, interactions between HIV, aging, and structural brain integrity become increasingly vital for understanding cognitive disorders. This study analyzed the effects of aging, HIV serostatus, and viral load on cognition and brain volumes in a large cohort of persons without HIV (PWoH), PWH with undetectable virus (PWHU) (≤50 copies/mL), and PWH with detectable virus (PHWD) (50 copies/mL). Cross-sectional and longitudinal data were included. Methods Cognitive composites (NPZ4) and brain volumes were obtained from 259 PWoH, 264 PWHU and 84 PWHD with a total of 841 sessions. A series of generalized additive mixed models explored group differences in the relationship between age and cognition, age and regional brain volumes, and interactions between age and brain volumes on cognition. Results PWoH and PWHU exhibited similar change in cognitive performance with age, while PWHD exhibited a steeper decline compared to both. While both PWH groups had significantly smaller regional brain volumes compared to PWoH, the slopes of volume loss with age were similar across all groups except in the lentiform regions. Smaller brain volumes and increased age interacted for greater cognitive decline in PWHD. Conclusion PWH who achieve viral suppression do not exhibit accelerated decline in cognition or brain volumes compared to PWoH, while PWHD may be at an increased risk for accelerated cognitive decline. These findings highlight the clinical importance of managing viral load in aging PWH and suggest that once viral suppression is achieved, changes to brain integrity are not accelerated compared to PWoH.
Kennedy et al. (2026) studied this question.