Erlandson Kristine M, Jiang Ying, Debanne Sara M, McComsey Grace A
1 Department of Medicine, Divisions of Infectious Diseases and Geriatric Medicine, University of Colorado , Aurora, Colorado.
2 Department of Epidemiology and Biostatistics, Case Western Reserve University , Cleveland, Ohio.
AIDS Res Hum Retroviruses. 2016 Apr;32(4):311-6. doi: 10.1089/AID.2015.0191. Epub 2015 Nov 16.
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% CD8(+)CD38(+)HLA-DR(+) T 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.
在感染HIV的人群中，炎症加剧和免疫激活与较低的骨矿物质密度（BMD）和瘦体重（LBM）相关。我们假设，瑞舒伐他汀减轻炎症与BMD和LBM的改善相关。未接受他汀类药物治疗且免疫激活增强（≥19% CD8(+)CD38(+)HLA-DR(+) T细胞）或炎症加剧（hsCRP≥2mg/升）的接受稳定抗逆转录病毒治疗的HIV感染者，被随机分为每日服用10mg瑞舒伐他汀组或安慰剂组，为期96周。在随机分配至瑞舒伐他汀组的72名参与者和安慰剂组的75名参与者中，BMD的相对变化（p>0.29）或脂肪变化（p≥0.19）无显著差异。在瑞舒伐他汀组中观察到LBM增加的趋势（p=0.059），肌酸激酶或自我报告的身体活动无差异（p≥0.10）。在多变量回归模型中，调整年龄、性别、种族、吸烟状况和可检测到的HIV-1病毒载量后，瑞舒伐他汀对LBM有显著的正向影响。较高的基线sCD163与第0至96周LBM的增加相关（p=0.023）；与基线IP-10水平较低的他汀类药物使用者相比，基线IP-10水平较高的使用者全身和腿部瘦体重变化更大（LBM分别为1.8%对-0.3%；p=0.028，腿部瘦体重分别为2.9%对-1.7%；p=0.012）。瑞舒伐他汀在96周的治疗中对BMD无毒性作用，对LBM可能有益。在为期2年的研究中，瑞舒伐他汀组LBM的维持对于延缓因衰老导致的肌肉量流失具有重要的临床意义。
