Statin use is associated with improved frailty trajectories in people with HIV

Statins have pleiotropic properties beyond LDL cholesterol reduction, including anti-inflammatory and immunomodulatory effects that may influence biological aging and frailty. The primary objective was to compare frailty trajectories in people with HIV using statins for cardiovascular prevention with those not using statins. Secondary objectives included differences in walking speed, short physical performance battery, and hand grip strength. This observational longitudinal study included people with HIV from the Modena HIV Metabolic Clinic (Italy) with no prior statin use at baseline and at least three frailty index (FI) assessments. Baseline was the first visit with a FI assessment; follow-up was the last visit. Statin users and non-users were matched for follow-up duration. Time 0 (T0) was defined as statin initiation. Frailty was assessed with a 34-item FI. To minimize collider bias, lipid variables were excluded from the FI due to their direct relationship with statin exposure. Frailty trajectories and secondary outcomes were analyzed using linear mixed models. Beta-estimates were multiplied by 100 to improve readability. Among 3,444 people with HIV (69% men; median age 44.7 years), 23.1% initiated statins for primary prevention and 2.0% for secondary prevention. Statin users had a more unfavorable cardiometabolic profile at T0. In adjusted models, statin use was associated with a reduction in FI over time (statin*time interaction β=-2.562, 95%-CI -3.176,-1.987). No associations were observed with secondary outcomes. Statins may improve frailty trajectories, mitigate aging-related decline and preserve physical function in people with HIV, supporting a broader role for statins in HIV care.