Plasma Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Biomarkers of Cognitive Decline in People With Human Immunodeficiency Virus.

Abstract

We examined the relationship between neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) and cognition in people with human immunodeficiency virus (HIV) at baseline and longitudinally. Plasma and clinical data were available from virally suppressed people with HIV (PWH) aged ≥45 years in the AIDS Clinical Trials Group HAILO study. Four neuropsychological assessments standardized and averaged (NPZ-4) represented cognition. Plasma collection date marked baseline; slope summarized longitudinal NPZ-4 changes. Linear regressions examined biomarkers associations with baseline NPZ-4 and longitudinal change. The study included 503 participants with a median age of 52 (interquartile range [IQR, 48-57]) years and observation of 6 (IQR, 5-7) years, and 26% had baseline cognitive impairment defined by HAILO. Cross-sectionally, higher NfL (β = -.76, P < .01) and GFAP (β = -.44, P = .02) were associated with worse NPZ-4. Longitudinally, the median NPZ-4 slope was 0.003 (IQR, -0.06 to 0.06) units/year with 48% demonstrating cognitive decline. Higher NfL (β = -.08, P < .01), but not GFAP (β = -.03, P = .08), was associated with cognitive decline. NfL and GFAP were associated with worse cognition cross-sectionally; only NfL was associated with cognitive decline. Their clinical utility remains uncertain given small effect sizes and should be studied in populations with more rapid decline.