ArticleAIDS (London, England)2026
Quantifying brain-age gap in people with HIV on antiretroviral therapy using plasma neurofilament light chain.
Article in AIDS (London, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveTo estimate the number of additional years above chronological age ("brain-age gap") at which observed plasma neurofilament light chain (NfL) levels in cognitively unimpaired people with HIV (PWH) correspond to published age-stratified standards from cognitively unimpaired individuals in the general population.
designSecondary analysis of the multicenter observational cohort study (ACTG HAILO) involving older, cognitively unimpaired PWH on antiretroviral therapy (ART).
methodsPlasma NfL concentrations were quantified using the Quanterix® Simoa assay in 340 PWH aged ≥45 years. Values were compared with two age-stratified reference standards from cognitively unimpaired general-population controls. The brain-age gap was estimated using a generalized logistic model with repeated measures so that 5% of observed NfL concentrations in PWH would exceed the reference upper 95 th percentile for the imputed age.
resultsMedian plasma NfL concentration was 10.1 pg/mL (IQR: 7.4-13.5). Using Simrén et al. standards, 24.1% (95% CI: 19.8-29.0) of observed values exceeded the age-specific upper 95 th percentile, and 10.0% (95% CI: 7.2-13.7) using Bornhorst et al. standards. Model-based results suggested brain age was 11.0 years (95% CI: 9.1-13.7) or 6.4 years (95% CI: 5.1-8.5) higher than chronological age, depending on the standard. The estimated brain-age gap was significantly greater in individuals with subsequent cognitive decline than in those without (Simrén: 13.0 vs. 8.4 years; Bornhorst: 7.6 vs. 5.0 years).
conclusionPlasma NfL reflects a substantial brain-age gap in cognitively unimpaired PWH on ART, supporting evidence of advanced aging. The brain-age gap was higher in PWH with subsequent cognitive decline.
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