Plasma Biomarkers and Cognitive Decline in HIV: Findings from Two U.S. Cohorts

With advances in antiretroviral treatment, the population of older people living with HIV (PLWH) is increasing rapidly, leading to a rise in cognitive impairment related to both HIV and aging. Plasma biomarkers have been extensively investigated as non-invasive tools to help detect neurodegeneration in PLWH. This review compares cross-sectional and longitudinal findings from two recent substudies conducted within U.S. cohorts, the AIDS Clinical Trials Group HAILO study and the Women's Interagency HIV Study (WIHS), both of which investigated the relationship between plasma biomarkers and cognitive performance in PLWH. This review focuses on the common biomarkers evaluated in both studies: neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). Both studies demonstrated longitudinal associations between elevated NfL levels and poor cognitive performance, particularly in processing speed. In contrast, GFAP showed inconsistent associations, suggesting its utility will be limited in clinical settings. Given that effect sizes across both studies ranged from small to modest, further validation in diverse aging cohorts with domain specific cognitive assessments is needed before routine clinical use.