Stability and Predictors of Phenotypic Age Acceleration among Virally Suppressed Asians with HIV over Five Years

Untreated human immunodeficiency virus (HIV) infection is associated with accelerated biological aging. Using phenotypic age (PhenoAge), a biological clock derived from clinical laboratory parameters, this retrospective study examines changes in phenotypic age acceleration (PAA) among people with HIV (PWH) receiving stable antiretroviral therapy (ART) over a five-year period. PhenoAge and PAA were calculated for clinic attendees at the Queen Elizabeth Hospital, Hong Kong, China at study baseline (T0), defined as at least one year after initiating ART with plasma HIV suppression (HIV RNA <50 copies/mL), and again five years later (T5). Demographic and clinical parameters included initial ART regimen, prior opportunistic infections, CD4+ T-cell count, CD4/CD8 ratio, and systemic immune-inflammation index (SII). Longitudinal changes in PAA, as well as correlates of PAA at T0 and its changes between T0 and T5, were analyzed. Of the 728 individuals selected (94% Asian; 88% male; median age, 40 years), the median PAA values at T0 and T5 were -0.38 and -0.47 years, indicating non-significant change over five years. At T0, female sex, CD4/CD8 ratio, prior opportunistic infections, non-nucleoside reverse transcriptase inhibitor (NNRTI)-based initial ART, and SII were significantly different among PAA percentile subgroups (p<0.05). Only the change in SII was significantly associated with the change in PAA between T0 and T5 (p<0.001). In this cohort, PAA appeared stable overall among PWH on suppressive ART, consistent with the benefits of sustained HIV suppression for biological aging. However, interindividual variability in PAA exists, and only SII was associated with its longitudinal changes.