Rosuvastatin Treatment Reduces Markers of Monocyte Activation in HIV-Infected Subjects on Antiretroviral Therapy

被引:125
作者
Funderburg, Nicholas T. [1 ]
Jiang, Ying [1 ]
Debanne, Sara M. [1 ]
Storer, Norma [1 ,2 ,3 ]
Labbato, Danielle [1 ,2 ,3 ]
Clagett, Brian [1 ]
Robinson, Janet [1 ,2 ]
Lederman, Michael M. [1 ,2 ]
McComsey, Grace A. [1 ,2 ,3 ]
机构
[1] Case Western Reserve Univ, Cleveland, OH 44106 USA
[2] Univ Hosp Cleveland, Case Med Ctr, Cleveland, OH 44106 USA
[3] Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA
基金
美国国家卫生研究院;
关键词
HIV-1; monocytes; tissue factor; rosuvastatin; INTIMA-MEDIA THICKNESS; TISSUE FACTOR; MICROBIAL TRANSLOCATION; CARDIOVASCULAR RISK; IMMUNE ACTIVATION; ATHEROSCLEROSIS; STATINS; INFLAMMATION; PROGRESSION; ATORVASTATIN;
D O I
10.1093/cid/cit748
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Statins, or 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, have anti-inflammatory effects that are independent of their lipid-lowering properties. Despite suppressive antiretroviral therapy (ART), elevated levels of immune activation and inflammation often persist. Methods. The Stopping Atherosclerosis and Treating Unhealthy Bone With Rosuvastatin in HIV (SATURN-HIV) trial is a randomized, double-blind, placebo-controlled study, designed to investigate the effects of rosuvastatin (10 mg/daily) on markers of cardiovascular disease risk in ART-treated human immunodeficiency virus (HIV)-infected subjects. A preplanned analysis was to assess changes in markers of immune activation at week 24. Subjects with low-density lipoprotein cholesterol <130 mg/dL and heightened immune activation (%CD8(+)CD38(+)HLA-DR+ >= 19%, or plasma high-sensitivity C-reactive protein >= 2 mg/L) were randomized to receive rosuvastatin or placebo. We measured plasma (soluble CD14 and CD163) and cellular markers of monocyte activation (proportions of monocyte subsets and tissue factor expression) and T-cell activation (expression of CD38, HLA-DR, and PD1). Results. After 24 weeks of rosuvastatin, we found significant decreases in plasma levels of soluble CD14 (-13.4% vs 1.2%, P=.002) and in proportions of tissue factor-positive patrolling (CD14(Dim)CD16(+)) monocytes (-38.8% vs -11.9%, P=.04) in rosuvastatin-treated vs placebo-treated subjects. These findings were independent of the lipid-lowering effect and the use of protease inhibitors. Rosuvastatin did not lead to any changes in levels of T-cell activation. Conclusions. Rosuvastatin treatment effectively lowered markers of monocyte activation in HIV-infected subjects on antiretroviral therapy.
引用
收藏
页码:588 / 595
页数:8
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