Methods: We performed a cross-sectional study of AA young adults aged 20-35 years with PHIV (N = 31) and seronegative controls (N = 30) using DNAm measured in whole blood and cognitive function measured by the NIH Toolbox. Illumina EPIC array was used to measure DNAm age and accelerated aging markers including epigenetic age acceleration (EAA), as well as extrinsic (EEAA) and intrinsic (IEAA) EAA.

Results: PHIV and controls did not differ by sex (45 vs. 43% male), chronological age (26.2 vs. 28.0 years), or ethnicity. Chronological age and DNAm age were correlated (r = 0.56, P < 0.01). PHIV had a higher mean EAA (2.86 ± 6.5 vs. -2.96 ± 3.9, P < 0.01) and EEAA (4.57 ± 13.0 vs. -4.72 ± 6.0, P < 0.01) than controls; however, IEAA was not different between groups. Among PHIV, EAA and EEAA were higher in those with HIV viral load ≥50 copies/mL than <50 copies/mL (EEA: 8.1 ± 5.2 vs. 0.11 ± 5.5, P = 0 < 0.01 and EEAA: 16.1 ± 10.6 vs. -1.83 ± 9.7, P < 0.01). We observed negative correlations (r = -0.36 to -0.31) between EEAA and executive function, attention, and language scores.

Conclusions: In conclusion, EAA in blood was observed in AA young adults with PHIV on ART using 2 measures, including EEAA which upweights the contribution of immunosenescent cell types. However, there was no evidence of age acceleration with a measure independent of cell type composition.