Prospective Evaluation of Antiviral Therapy and Cardiac Health

描述(由申请人提供)： 这项研究提案的总体目标是前瞻性地检查三种现代抗逆转录病毒疗法(ART)治疗策略对人类免疫缺陷病毒(HIV)感染的初治患者动脉粥样硬化进展的影响。拟议的研究将检验和量化抗逆转录病毒治疗、心血管疾病(CVD)危险因素、免疫激活和炎症在艾滋病毒感染者动脉损伤和动脉粥样硬化进展中的作用。联合首席调查员是一名传染病专家和一名心脏病专家，他们在调查艾滋病毒患者的心血管风险方面具有专业知识。他们已经组建了一个多学科的研究团队，其中包括两名艾滋病毒治疗专家，两名在动脉粥样硬化成像和血脂方面有专长的心脏病专家，一名内分泌学家，一名免疫学家，以及一名心血管基础科学家，他们将与美国国家过敏和传染病研究所艾滋病临床试验组艾滋病临床试验组合作，进行一项前瞻性的A5257子研究，“三种紧凑的非核苷逆转录酶抑制剂节省抗逆转录病毒方案治疗未感染HIV-1的志愿者的比较研究。”A5257是ART疗效的前瞻性随机临床试验(RCT)。在ACTG内的前瞻性随机临床试验中嵌入动脉损伤的结构和功能标记物及其决定因素的分析，是了解传统和艾滋病毒相关因素对艾滋病毒携带者动脉粥样硬化进展的贡献的有效和成本效益高的方法。该提案包括以下临床和机制目标：目标1(临床)：检查三种当代初步ART治疗策略在三年内对动脉粥样硬化进展的影响。目的2(机制和临床)：在治疗的第一年，检查三种当代的初始ART治疗策略对内皮功能的影响的大小和时间进程。目的3(机械学)：研究ART相关代谢变化对内皮功能和动脉粥样硬化进展的影响。目的4(机械学)：研究ART相关免疫功能改变和炎症对内皮功能和动脉粥样硬化进展的影响。据估计，全世界有3300万艾滋病毒感染者。艾滋病毒感染的治疗在过去20年中有了显著的改善，但人们越来越担心艾滋病毒治疗和慢性艾滋病毒感染可能会增加艾滋病毒携带者患心血管疾病的风险。拟议的研究将有助于确定增加艾滋病毒患者心血管疾病风险的因素，并确定在艾滋病毒感染的背景下降低长期心血管疾病风险的最佳治疗策略。(摘要结束)

DESCRIPTION (provided by applicant): The overall goal of this research proposal is to prospectively examine the impact of three modern antiretroviral therapy (ART) treatment strategies on the progression of atherosclerosis in treatment-na¿ve individuals with human immunodeficiency virus (HIV) infection. The studies proposed will examine and quantify the contributions of ART, cardiovascular disease (CVD) risk factors, immune activation and inflammation on arterial injury and atherosclerosis progression in HIV-infected individuals. The co-principal investigators are an infectious disease specialist and a cardiologist with expertise in the investigation of CVD risk in patients with HIV. They have assembled a multidisciplinary team of investigators that includes two experts in the treatment of HIV, two cardiologists with expertise in atherosclerosis imaging and lipids, an endocrinologist, and an immunologist, and a cardiovascular basic scientist, who, in collaboration with the National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group AIDS Clinical Trials Group, will conduct a prospective substudy of A5257, "A Comparative Study of Three Compact, Non-Nucleoside Reverse Transcriptase Inhibitor Sparing Antiretroviral Regimens for the Treatment Naive HIV-1 Infected Volunteers." A5257 is a prospective, randomized clinical trial (RCT) of ART efficacy. Embedding analyses of structural and functional markers of arterial injury and their determinants in a prospective, randomized clinical trial within the ACTG is an efficient and cost-effective approach to understanding the contributions of traditional and HIV-related factors to atherosclerosis progression in individuals with HIV. The proposal includes the following clinical and mechanistic aims: AIM 1 (Clinical): To examine the effects of three contemporary initial ART treatment strategies on atherosclerosis progression over three years. AIM 2 (Mechanistic and clinical): To examine the magnitude and time course of the effects of three contemporary initial ART treatment strategies on endothelial function during the first year of therapy. AIM 3 (Mechanistic): To examine the effects of ART-related metabolic changes on endothelial function and atherosclerosis progression. AIM 4 (Mechanistic): To examine the effects of ART-related changes in immune function and inflammation on endothelial function and atherosclerosis progression. There are estimated to be 33 million people worldwide who are living with HIV infection. Treatment for HIV infection has improved dramatically over the past twenty years, however there is growing concern that HIV treatments and chronic HIV infection might increase the risk of cardiovascular disease in people living with HIV. The proposed research will help identify the factors that increase the risk of cardiovascular disease in HIV patients and determine the optimal treatment strategies to reduce long-term cardiovascular disease risk in the setting of HIV infection. (End of Abstract)