The GrimAge clock corresponds to brain ageing and social determinants of health in people with HIV

Background DNA methylation (DNAm)-based epigenetic clocks can measure biological ageing. However, newer epigenetic clocks sensitive to morbidity, mortality, and longitudinal change have not been compared to brain health biomarkers in virally suppressed people with HIV (PWH) and without HIV (PWoH). Methods Participants in this case-control study underwent blood draws, brain MRI, and neuropsychological testing. Four DNAm-based epigenetic clocks were calculated: GrimAge (mortality-predictive), PhenoAge (morbidity-sensitive), DunedinPACE (longitudinal), and DNAm telomere length. Clocks were correlated with MRI features and cognitive domains. Neighbourhood socioeconomics, unemployment, early life stress, education, and medical comorbidities were examined as risk factors for epigenetic ageing. Findings 126 virologically suppressed PWH (age = 53.8 ± 12.2 yr) and 145 PWoH (age = 48.1 ± 16.4) participated. Elevated GrimAge ( p < 0.001; +1.8 years), PhenoAge ( p = 0.002; +2.4 years), and DunedinPACE ( p < 0.001; +5.1% ageing rate) were found for PWH vs. PWoH, controlling for demographic factors. Predicted telomere length was shorter for PWH vs. PWoH ( p < 0.001). GrimAge correlated with brain age gap ( p = 0.002; +5.9 years of brain age per decade of GrimAge) across all participants. Epigenetic clocks were linked to poorer cognition in specific domains. Area Deprivation Index was positively associated with GrimAge ( p = 0.001) in PWH, while education was negatively associated ( p = 0.002). Cardiovascular risk was associated with increased GrimAge ( p = 0.008) across all participants. Interpretation Biological age alterations persist in PWH despite viral suppression, as revealed by multiple epigenetic clocks. GrimAge and other clocks are linked with brain morphology and cognitive dysfunction. Results suggest that biological ageing is influenced by modifiable social and comorbid risk factors. Funding United States National Institutes of Health (National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Nursing Research) and amfAR, The Foundation for AIDS Research.