Prospective Evaluation of Antiviral Therapy and Cardiac Health

描述（由申请人提供）： 这项研究的总体目标是前瞻性地研究三种现代抗逆转录病毒治疗（ART）策略对人类免疫缺陷病毒（HIV）感染的初治个体动脉粥样硬化进展的影响。拟议的研究将检查和量化ART，心血管疾病（CVD）风险因素，免疫激活和炎症对艾滋病毒感染者动脉损伤和动脉粥样硬化进展的贡献。联合主要研究者是一名传染病专家和一名心脏病专家，在艾滋病毒患者的心血管疾病风险调查方面拥有专业知识。他们组建了一个多学科的研究小组，其中包括两名治疗艾滋病毒的专家，两名心脏病专家，他们在动脉粥样硬化成像和脂质方面具有专业知识，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，他们与国家过敏和传染病研究所艾滋病临床试验组合作，将对A5257进行前瞻性子研究，“三种紧凑型非核苷逆转录酶抑制剂保留抗逆转录病毒方案对未经治疗的HIV-1感染志愿者的比较研究。A5257是一项关于ART疗效的前瞻性随机临床试验（RCT）。在ACTG的前瞻性随机临床试验中，对动脉损伤的结构和功能标志物及其决定因素进行嵌入分析，是了解传统因素和HIV相关因素对HIV患者动脉粥样硬化进展的贡献的一种有效且具有成本效益的方法。该提案包括以下临床和机制目标：目的1（临床）：检查三种当代初始ART治疗策略对动脉粥样硬化进展的影响超过三年。目的2（机制和临床）：在治疗的第一年，检查三种当代初始ART治疗策略对内皮功能影响的程度和时间过程。目的3（机制）：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。目标4（机械）：研究ART相关免疫功能和炎症变化对内皮功能和动脉粥样硬化进展的影响。据估计，全世界有3 300万人感染艾滋病毒。在过去的二十年里，艾滋病毒感染的治疗有了显著的改善，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感染者患心血管疾病的风险。这项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，并确定最佳治疗策略，以降低艾滋病毒感染背景下的长期心血管疾病风险。(End摘要）

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)