Blood-based Alzheimer's disease biomarkers and cognitive trajectories in older people with HIV with undetectable viral loads.

INTRODUCTION: Cognitive impairment among people with HIV (PWH) remains common, yet underlying mechanisms remain unclear. Alzheimer's disease (AD) is the leading cause of dementia, and blood-based biomarkers offer a promising diagnostic alternative. We evaluated phosphorylated-tau 217 (p-tau217), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) as predictors of cognitive decline among virologically suppressed older PWH. METHODS: Thai PWH aged ≥50 years with plasma viral loads <50 copies/mL completed the Montreal Cognitive Assessment (MoCA) at baseline (2015-2017) and a follow-up visit (2021-2024). Associations between each biomarker and cognitive trajectories were assessed using multivariate mixed-effects models. RESULTS: Among 255 participants followed for a median of 5.9 years, those in Q4 of p-tau217 and GFAP had greater MoCA decline than Q1-3 (p-tau217: -3.3 vs. -1.4, p-interaction = 0.02; GFAP: -2.9 vs. -1.3, p-interaction = 0.03). DISCUSSION: Elevated p-tau217 and GFAP predict cognitive decline in PWH, underscoring AD and inflammatory biomarker relevance.