Objectives : Despite successful ART, people living with HIV (PLWH) may show signs of premature/accentuated aging. We compared established biomarkers of aging in PLWH, appropriately chosen HIV-negative individuals, and blood donors, and explored factors associated with biological age advancement.
Design : Cross-sectional analysis of 134 PLWH on suppressive ART, 79 lifestyle-comparable HIV-negative controls aged 45 years or older from the COBRA cohort, and 35 age-matched blood donors.

Methods : Biological age was estimated using a validated algorithm based on 10
biomarkers. Associations between ‘age advancement’ (biological minus chronological
age) and HIV status/parameters, lifestyle, CMV, HBV and HCV infections were investigated using linear regression.

Results: The average (95% CI) age advancement was greater in both HIV-positive [13.2 (11.6–14.9) years] and HIV-negative [5.5 (3.8–7.2) years] COBRA participants compared with blood donors [- 7.0 (- 4.1 to - 9.9) years, both P<0.001)], but also in HIV-positive compared with HIV-negative participants (P<0.001). Chronic HBV, higher anti-CMV IgG titer and CD8+ T-cell count were each associated with increased age advancement, independently of HIV-status/group. Among HIV-positive participants, age advancement was increased by 3.5 (0.1–6.8) years among those with nadir CD4+ T-cell count <200 cells/ml and by 0.1 (0.06–0.2) years for each additional month of exposure to saquinavir.

Conclusion: Both treated PLWH and lifestyle-comparable HIV-negative individuals
show signs of age advancement compared with blood donors, to which persistent CMV,
HBV co-infection and CD8+ T-cell activation may have contributed. Age advancement
remained greatest in PLWH and was related to prior immunodeficiency and cumulative
saquinavir exposure.