The SATURN-HIV (Stopping Atherosclerosis and Treating Unhealthy bone with RosuvastatiN in HIV) study is a randomized, double-blinded, placebo-controlled trial designed to measure the impact of daily rosuvastatin at 10 mg on cardiovascular disease and skeletal health.
Eligible individuals were HIV-infected adults at least 18 years of age with a fasting low-density lipoprotein (LDL) cholesterol of 130 mg/dl or less and either a high-sensitivity C-reactive protein (hsCRP) level of at least 2 mg/l and/or at least 19% activated CD8 + T-cells (CD8 + CD38 + HLA - DR + ), stable ART for at least 12 weeks with cumulative ART duration of at least 6 months, HIV-1 RNA of 1000 copies/ml or less and no history of fragility fractures.
Individuals were randomized 1:1 to rosuvastatin 10 mg daily or placebo for 96 weeks. Randomization was stratified by protease inhibitor use at study entry, by the presence or absence of osteopenia (at either hip or spine) at study entry and by the presence or absence of coronary calcifications by computed tomography (CT) scan.
The bone and body composition sub-study was a prespecified interim analysis at 48 weeks of the SATURN-HIV study. Between-group and within-group differences were compared; multivariable regression models were constructed.
72 individuals were randomized to statin therapy and 75 to placebo. Overall, the median age was 47 years, the median CD4 + lymphocyte count was 613 cells/ml and 78% had an HIV-1 RNA less than 50 copies/ml. The majority of participants were male, African-American, smokers and taking tenofovir-containing ART regimens. Thirty-five (24%) individuals met criteria for osteopenia or osteoporosis at the hip and 32 (22%) met criteria for osteopenia or osteoporosis at the lumbar spine.
Modest 48-week relative increases in trochanter BMD [0.9%; 95% confidence interval (95% CI) -0.9 to 0.6] and total hip BMD (0.6%; 95% CI 0.0ā1.1) in the statin arm were significantly greater than placebo (P<0.05).
Relative increases in total body, trunk and limb fat were similar between statin and placebo arms (Pā„0.58). Although a significant gain in leg lean mass was seen in the statin arm, this was not significantly different compared with placebo (P=0.36).
The estimated difference in hip BMD with assignment to statin was 0.92% (0.15, 1.68%; P=0.019) in a model, including age, race, sex and smoking status. The estimated difference in hip BMD with statin use did not change significantly when including family history of hip fracture; use of tenofovir; duration of protease inhibitor; HIV-1 RNA; current or nadir CD4 + lymphocyte count; baseline or 48 week relative change in trunk or limb fat; or total lean mass. The estimated change in BMD with statin use was strengthened only by inclusion of baseline [estimate 0.96% (0.22 to 1.7%); P=0.01] and week 48 change in sTNFR-1 [estimate 1.0% (0.25 to 1.79%); P=0.009].
Statins are potent cholesterol-lowering drugs recognized for the additional anti-inflammatory mechanisms. This study is the first randomized intervention of statin therapy to assess the impact on changes in BMD, fat and lean mass among effectively treated, HIV-infected adults with normal LDL cholesterol and increased levels of inflammation or immune activation.
In conclusion, the improvement seen in total hip BMD after 48 weeks of rosuvastatin therapy support further potential benefits of statin therapy in HIV, beyond a reduction of cardiovascular risk. Randomized assignment to rosuvastatin resulted in small but significant improvements in total hip BMD compared with placebo, which was independently associated with changes in sTNFR-1, but not other inflammation or activation markers, and independent of traditional bone risk factors. Findings provide evidence that statins may have additional benefits in HIV-infected persons beyond the reduction in cardiovascular risk.
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