Effect of atorvastatin on frailty-related outcomes, body composition and biochemical markers in people living with HIV: A randomized, double-blind, placebo-controlled clinical trial

Abstract

Frailty is increasingly recognized among people living with human immunodeficiency virus (PLHIV) despite antiretroviral therapy (ART). Statins, including atorvastatin, have pleiotropic metabolic and anti-inflammatory effects that may influence frailty-related pathways, although their impact on frailty in PLHIV remains unclear. The aim of this study was to evaluate the effect of atorvastatin on frailty status, its components, body composition, and related laboratory parameters in PLHIV receiving ART. This randomized, double-blind, placebo-controlled clinical trial included PLHIV with frailty or pre-frailty status at baseline. Participants were assigned to receive atorvastatin 40 mg once daily or placebo for 12 weeks. The primary outcome was frailty incidence, assessed using Cardiovascular Health Study (CHS)-based criteria and the Frailty Index (FI), including combined CHS–FI frailty status and CHS-based frailty components. Secondary outcomes included body composition, total cholesterol, and serum myostatin levels. Statistical analyses were performed using unadjusted and adjusted models. After 12 weeks, FI scores improved significantly within both the placebo (p<0.001) and atorvastatin groups (p=0.009). Serum myostatin levels also decreased significantly within both groups (both p<0.001). However, no significant between-group differences were observed for changes in CHS-based fit status (p=0.201), FI-based fit status (p=0.194), combined CHS–FI fit status (p=0.153), FI score (p=0.292), unintentional weight loss (p=0.225), handgrip strength (p=0.785), exhaustion (p=0.227), gait speed (p=0.333), physical activity limitation (p=0.479), total cholesterol (p=0.586), or serum myostatin levels (p=0.310) in the fully adjusted model. Atorvastatin was significantly associated with reductions in body weight (p=0.029) and BMI (p=0.030), whereas no significant effects were observed on body fat, water mass, muscle mass, or bone mass in the fully adjusted model. In conclusion, atorvastatin did not improve frailty status, frailty-related components, total cholesterol, or serum myostatin levels compared with placebo in PLHIV receiving ART. Although reductions in body weight and BMI were observed, these changes were not accompanied by improvement in frailty outcomes. Future studies with larger sample sizes, longer follow-up periods, and more detailed assessments of physical activity, diet, ART regimens, and inflammatory markers are needed to clarify the role of atorvastatin in frailty-related outcomes among PLHIV.