Effects of 96 Weeks of Rosuvastatin on Bone, Muscle, and Fat in HIV-Infected Adults on Effective Antiretroviral Therapy

Abstract

Heightened inflammation and immune activation are associated with lower bone mineral density (BMD) and lean body mass (LBM) among HIV-infected persons. We hypothesized that a reduction in inflammation with rosuvastatin would be associated with improvements in BMD and LBM. HIV-infected participants on stable antiretroviral therapy without statin indication and with heightened immune activation ( ‡19% CD8T cells) or inflammation (hsCRP ‡2 mg/liter) were randomized to rosuvastatin 10 mg daily or placebo for 96 weeks. Among 72 participants randomized to rosuvastatin and 75 to placebo, there were no significant differences in the relative changes in BMD ( p > 0.29) or in fat ( p ‡ 0.19). A trend toward increased LBM ( p = 0.059) was seen in the rosuvastatin arm without differences in creatinine kinase or self-reported physical activity ( p ‡ 0.10). In a multivariable regression model, rosuvastatin was associated with a significant positive effect on LBM after adjusting for age, sex, race, smoking status, and detectable HIV-1 viral load. Higher baseline sCD163 correlated with increases in LBM from weeks 0 to 96 ( p = 0.023); greater changes in total and leg lean mass were seen among statin users with higher compared to lower baseline IP-10 levels (LBM 1.8 vs. -0.3%; p = 0.028 and leg lean mass 2.9 vs. -1.7%; p = 0.012). Rosuvastatin is associated with an absence of toxicity on BMD and a potential benefit on LBM over 96 weeks of therapy. The preservation of LBM in the rosuvastatin arm over the 2 years of the study is of major clinical relevance in delaying loss of muscle mass with aging.

Pharmacologic approaches to the prevention and management of low bone mineral density in HIV-infected patients

“…A recent clinical trial involving 72 PLWH demonstrated a modest 48-week relative increase in trochanter BMD (0.9%; 95% CI, À0.9-0.6%) and total hip BMD (0.6%; 95% CI, 0.0-1.1%) in the rosuvastatin arm that was significantly greater than the effect observed with placebo (P < 0.05) [45 & ]. However, despite the promising results at week 48, data at week 96 did not find differences in BMD between rosuvastatin and placebo groups [46]. These findings with rosuvastatin are in line with studies failing to show a conclusive direct association between increased inflammation and loss of BMD in PLWH [47].…”

Understanding mechanisms to promote successful aging in persons living with HIV

“…It must be noted, however, that other studies have not shown a mortality benefit with statin use (Overton et al, 2013;Krsak et al, 2015;Rasmussen et al, 2013). Statin therapy has also not been shown to reduce bone loss in a randomized trial of HIV-positive subjects receiving suppressive ART (Erlandson et al, 2016). Of note, retrospective studies have not shown a benefit of statin therapy for CVD risk reduction (e.g., myocardial infarction, stroke) among individuals on stable ART (Overton et al, 2013;Krsak et al, 2015).…”

Bone Loss in HIV Infection

“…In addition, the 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) simvastatin has been shown to increase osteoblast activity and decrease osteoclastogenesis, and is associated with increased fracture healing in in vivo animal models [124], while pravastatin has been shown to prevent PI-induced senescence in MSCs and restore osteoblastic potential in vitro [89]. Clinically however, in HIV-infected individuals on stable cART who had heightened immune activation, treatment with rosuvastatin for 96 weeks was not associated with any changes in BMD, although it was associated with improvement in lean body mass [125]. More data on the BMD effects of these medications in HIV-infected patients are needed.…”