Funderburg Nicholas T, Jiang Ying, Debanne Sara M, Storer Norma, Labbato Danielle, Clagett Brian, Robinson Janet, Lederman Michael M, McComsey Grace A
Case Western Reserve University.
Clin Infect Dis. 2014 Feb;58(4):588-95. doi: 10.1093/cid/cit748. Epub 2013 Nov 18.
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.
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).
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.
Rosuvastatin treatment effectively lowered markers of monocyte activation in HIV-infected subjects on antiretroviral therapy.
NCT01218802.
他汀类药物，即3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂，具有独立于其降脂特性的抗炎作用。尽管采用了抑制性抗逆转录病毒疗法（ART），免疫激活和炎症水平往往仍然升高。
在HIV感染者中使用瑞舒伐他汀预防动脉粥样硬化和治疗不健康骨骼（SATURN-HIV）试验是一项随机、双盲、安慰剂对照研究，旨在调查瑞舒伐他汀（每日10毫克）对接受ART治疗的人类免疫缺陷病毒（HIV）感染者心血管疾病风险标志物的影响。一项预先计划的分析是评估第24周时免疫激活标志物的变化。低密度脂蛋白胆固醇<130毫克/分升且免疫激活增强（%CD8(+)CD38(+)HLA-DR(+)≥19%，或血浆高敏C反应蛋白≥2毫克/升）的受试者被随机分配接受瑞舒伐他汀或安慰剂。我们测量了血浆（可溶性CD14和CD163）和单核细胞激活的细胞标志物（单核细胞亚群比例和组织因子表达）以及T细胞激活（CD38、HLA-DR和PD1的表达）。
瑞舒伐他汀治疗24周后，我们发现与安慰剂治疗的受试者相比，瑞舒伐他汀治疗的受试者血浆可溶性CD14水平显著降低（-13.4%对1.2%，P = 0.002），组织因子阳性巡逻（CD14(Dim)CD16(+)）单核细胞比例显著降低（-38.8%对-11.9%，P = 0.04）。这些发现独立于降脂作用和蛋白酶抑制剂的使用。瑞舒伐他汀未导致T细胞激活水平发生任何变化。
瑞舒伐他汀治疗有效降低了接受抗逆转录病毒治疗的HIV感染者的单核细胞激活标志物。
NCT01218802。
