Accelerated Brain Aging and Cerebral Blood Flow Reduction in Persons with Human Immunodeficiency Virus

Background: Persons with human immunodeficiency virus (PWH) are characterized by altered brain structure and function. As they attain normal lifespans, it has become crucial to understand potential interactions between human immunodeficiency virus (HIV) and aging. However, it remains unclear how brain aging varies with viral load (VL). Methods: In this study, we compare magnetic resonance imaging (MRI) biomarkers among PWH with undetectable VL (UVL; ≤50 genomic copies/mL; n = 230), PWH with detectable VL (DVL; >50 copies/mL; n = 93), and HIV-uninfected (HIV-) controls (n = 206). To quantify gray matter cerebral blood flow (CBF), we utilized arterial spin labeling. To measure structural aging, we used a publicly available deep learning algorithm to estimate brain age from T1-weighted MRI. Cognitive performance was measured using a neuropsychological battery covering 5 domains. Results: Associations between age and CBF varied with VL. Older PWH with DVL had reduced CBF vs PWH with UVL (P =. 02). Structurally predicted brain aging was accelerated in PWH vs HIV- controls regardless of VL (P <. 001). Overall, PWH had impaired learning, executive function, psychomotor speed, and language compared to HIV- controls. Structural brain aging was associated with reduced psychomotor speed (P <. 001). Conclusions: Brain aging in HIV is multifaceted. CBF depends on age and current VL and is improved by medication adherence. By contrast, structural aging is an indicator of cognitive function and reflects serostatus rather than current VL.