Department of Public Health Sciences, University of California Davis, Davis, California, USA.
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
AIDS Res Hum Retroviruses. 2021 May;37(5):357-367. doi: 10.1089/AID.2020.0127. Epub 2020 Dec 29.
Immune activation and inflammation are hallmarks of chronic HIV infection and are etiologically linked to major causes of morbidity and mortality among HIV-infected persons, including coronary artery disease and cancer. Systemic immune activation is dampened, but not resolved, with use of combination antiretroviral therapy (cART). Statins are cardioprotective drugs that also appear to have immunomodulatory and anti-inflammatory properties. We sought to understand the association between statin use, cART, and levels of circulating immune markers in a longitudinal cohort study. From 2004 to 2009, statin use was ascertained in male participants of the Multicenter AIDS Cohort Study (MACS) using interviewer-administered questionnaires. Twenty-four circulating markers of immune activation and inflammation were measured in archived serial samples from a subset of cohort members using multiplex assays. Propensity-adjusted generalized gamma models were used to compare biomarkers' distributions by statin use, and multivariable linear regression models were used to assess the effect of initiating statin on these biomarkers. Overall, 1,031 cART-exposed individuals with HIV infection were included in this study. Statin use was reported by 31.5% of cART-exposed participants. Compared to nonstatin users on cART, statin users on cART had lower levels of IP-10, IL-10, and IL-12p70, and the effect of statin use was decreased in participants using lipophilic statins (atorvastatin, simvastatin, fluvastatin, or lovastatin); these results were statistically significant ( < .05). Among cART users not on aspirin, starting statins decreased levels of high sensitivity c-reactive protein (hsCRP), IL-12p70, and IL-6. Statin therapy is associated with reduced levels of certain biomarkers of immune activation and inflammation in cART users, which may contribute to a lower burden of disease.
免疫激活和炎症是慢性 HIV 感染的标志，也是导致 HIV 感染者发病率和死亡率的主要原因，包括冠心病和癌症。联合抗逆转录病毒疗法 (cART) 可抑制系统性免疫激活，但不能完全消除。他汀类药物是具有心脏保护作用的药物，也具有免疫调节和抗炎作用。我们试图在一项纵向队列研究中了解他汀类药物的使用、cART 和循环免疫标志物水平之间的关联。2004 年至 2009 年，使用访谈者管理的问卷在多中心艾滋病队列研究 (MACS) 的男性参与者中确定他汀类药物的使用情况。使用多重分析测定法在队列成员的存档系列样本中测量了 24 种循环免疫激活和炎症标志物。使用倾向评分调整的广义伽马模型比较了他汀类药物使用的生物标志物分布，并使用多变量线性回归模型评估了开始使用他汀类药物对这些生物标志物的影响。总体而言，本研究纳入了 1031 名接受 cART 治疗的 HIV 感染个体。接受 cART 治疗的参与者中有 31.5%报告使用了他汀类药物。与接受 cART 的非他汀类药物使用者相比，接受 cART 的他汀类药物使用者的 IP-10、IL-10 和 IL-12p70 水平较低，而使用亲脂性他汀类药物（阿托伐他汀、辛伐他汀、氟伐他汀或洛伐他汀）的他汀类药物使用者的效果降低；这些结果具有统计学意义（ < .05）。在未服用阿司匹林的 cART 使用者中，开始使用他汀类药物可降低高敏 C 反应蛋白 (hsCRP)、IL-12p70 和 IL-6 的水平。他汀类药物治疗与 cART 使用者某些免疫激活和炎症生物标志物水平降低有关，这可能有助于降低疾病负担。
