Rosuvastatin Linked to Small 96-Week Gain in Lean Body Mass for People on HIV Treatment
Taking rosuvastatin for 96 weeks slightly improved lean body mass but had little impact on bone mineral density (BMD) or fat in a small placebo-controlled trial enrolling individuals on HIV treatment without a statin indication. SATURN-HIV investigators believe the gain in lean body mass "is of major clinical relevance in delaying loss of muscle mass with aging," according to the study.
Persistent inflammation and immune activation in patients responding to antiretroviral therapy may contribute to low BMD and lean body mass in an aging HIV population. The anti-inflammatory activity of statins could help diminish this low-grade inflammation and immune activation and so affect BMD and lean body mass. Research in older HIV-negative people does link statin use to BMD and lean body mass benefits.
To see if statins have the same benefits in people with HIV, researchers randomized 147 adults on stable antiretroviral therapy to 96 weeks of rosuvastatin (10 mg daily) or to placebo. Participants in this double-blind trial had normal low-density lipoprotein cholesterol and had heightened inflammation or immune activation confirmed by standard markers. Everyone had taken antiretroviral therapy for at least six months with a viral load at or below 1000 copies/mL, and no one had a history of fragility fracture, a chronic inflammatory condition (other than HIV) or myocardial infarction.
The researchers used whole-body, lumbar spine and left hip DXA scans to calculate fat mass, lean body mass and BMD at baseline, week 48, and week 96. They used linear regression analysis adjusted for age, sex, race, smoking and viral load to explore the impact of variables on the association between statin use and change in lean body mass.
Median age of the study group stood at 47 years and median body mass index at a moderately overweight 26.7 kg/m2. More than three-quarters of study participants were men, 70% were African American, about 65% smoked and nearly 90% were taking a tenofovir-containing regimen. Nine participants in the rosuvastatin arm and 19 in the placebo arm withdrew before week 96.
BMD changed little through 96 weeks, and changes at that point did not differ significantly between the rosuvastatin and placebo arms at any anatomic site. Total body fat, trunk fat and limb fat rose almost 10% through 96 weeks, and these changes did not differ between study arms.
Mean lean body mass rose 0.8% in the rosuvastatin group (95% confidence interval [CI] 0.5% to 0.9%, P = .091) and decreased 0.5% in the placebo arm (95% CI -1.5% to 0.5%, P = .35). The between-arm difference in lean body mass change approached statistical significance (P = .059).
The multivariable model linked rosuvastatin to increased lean body mass through 96 weeks (estimate 1.43%, 95% CI 0.17% to 2.7%, P = .026). The same model linked African-American race to decreased lean body mass (estimate -1.71%, 95% CI -3.07% to -0.35%, P = .014). Age, male sex, smoking and viral load did not predict lean body mass change in this analysis. In an analysis limited to participants randomized to rosuvastatin, those with higher baseline levels of IP-10 (an immune activation marker) had a greater change in total lean body mass (1.8%, 95% CI 0.6% to 3.0%, P = .028) and leg lean mass (2.9%, 95% CI 0.7% to 5.1%, P = .012).
The researchers suggest their findings "provide reassurance that rosuvastatin did not appear to exacerbate the impairments in BMD, fat distribution, or [lean body mass] in HIV-infected persons." And, because research in the general population indicates a median lean body mass loss of nearly 0.5% yearly in men and 0.4% yearly in women, the SATURN team proposes that "the preservation of [lean body mass] in the rosuvastatin arm over the 2 years of the study could be of major clinical relevance in delaying loss of muscle mass with aging."