Mechanisms of Atherosclerosis and CVD in HIV+ Women

HIV 女性动脉粥样硬化和 CVD 的机制

• 批准号: 7062610
• 负责人: Robert C Kaplan
• 金额: $ 63.33万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7062610
• 关键词: HAART (highly active antiretroviral therapy); HIV infections; angiocardioultrasonography; atherosclerosis; blood lipoprotein metabolism; cardiovascular disorder epidemiology; cardiovascular disorder risk; clinical research; comorbidity; disease /disorder etiology; drug adverse effect; female; glucose tolerance; human subject; inflammation; medical complication; pathologic process; patient oriented research

DESCRIPTION (provided by applicant): As survival among HIV-infected persons has improved markedly in the era of highly-active antiretroviral therapy (HAART), clarifying the long-term effects of both HIV infection and its treatment is increasingly important. Extensive data suggest that HIV-infected patients have premature atherosclerosis and cardiovascular events. However, several major questions regarding the causal mechanisms and clinical relevance of these findings remain unanswered. Atherosclerosis may be due to HIV infection, use of antiretroviral medications, or both. The well-known metabolic effects of protease inhibitors (Pis) or other antiretroviral drugs may promote atherosclerosis, or there may also be direct vascular effects of these medications. HIV lipodystrophy syndrome, either due to medications or HIV itself, may also be a contributing factor. Little is known about the potential atherogenic effects of sustained elevations of inflammation markers in HIV infection. Moreover, women, African-Americans and Hispanics have been underrepresented in studies of atherosclerosis and CVD in HIV infection. The overall goal of this investigation is to assess whether HIV-infected women have accelerated atherosclerosis and to identify potential mediators of atherosclerosis in HIV infection. Within the Women's Interagency HIV Study (WIHS) cohort, this study will assess progression of subclinical atherosclerosis using B-mode ultrasound imaging methods to measure changes over time in carotid artery intima-media thickness (IMT). The study will include 250 women with HIV infection and 250 HIV-negative controls at the six WIHS clinic sites. Carotid ultrasounds will be obtained at annual intervals over 48 months, and rate of IMT progression will be interpreted centrally at the Core Imaging Facility. The extensive WIHS database, featuring data collected at study visits every six months, will be used to evaluate whether IMT progression may be associated with HIV infection; use of HAART, Pis, or other antiretrovirals; occurrence of AIDS, high HIV viral load, and low CD4 count; metabolic abnormalities including diabetes, lipodystrophy, and hypertriglyceridemia; and inflammation markers and endothelial adhesion molecules including high-sensitivity CRP, E-selectin, and ICAM-1. This investigation will have major implications for the development of strategies to predict, prevent, or reverse atherosclerosis in HIV- infected women.

描述（由申请人提供）：在高度活跃的抗逆转录病毒疗法（HAART）的时代，艾滋病毒感染者之间的生存显着改善，阐明了HIV感染及其治疗的长期影响越来越重要。大量数据表明，感染HIV的患者患有过早的动脉粥样硬化和心血管事件。但是，有关这些发现的因果机制和临床相关性的几个主要问题仍未得到解答。动脉粥样硬化可能是由于HIV感染，抗逆转录病毒药物的使用或两者兼而有之。蛋白酶抑制剂（PIS）或其他抗逆转录病毒药物的众所周知的代谢作用可能会促进动脉粥样硬化，或者这些药物也可能有直接的血管作用。 HIV脂肪营养不良综合征是由于药物或HIV本身，也可能是一个促成因素。关于艾滋病毒感染中炎症标志物持续升高的潜在动脉粥样硬化作用知之甚少。此外，在HIV感染中，妇女，非裔美国人和西班牙裔人的动脉粥样硬化和CVD的研究不足。这项研究的总体目的是评估感染HIV的妇女是否加速了动脉粥样硬化并确定HIV感染中动脉粥样硬化的潜在介体。在妇女的妇女间艾滋病毒研究（WIHS）队列中，本研究将使用B模式超声成像方法评估亚临床动脉粥样硬化的进展，以测量颈动脉内膜膜厚度（IMT）中随时间的变化。该研究将包括250名患有HIV感染的女性和250个WIHS诊所部位的HIV阴性控制。颈动脉超声将在48个月内每年以每年的间隔获得，IMT进展速度将在核心成像设施中心解释。每六个月收集在研究访问中收集的数据的广泛的WIHS数据库将用于评估IMT进展是否可能与HIV感染有关；使用HAART，PIS或其他抗逆转录病毒； AIDS的发生，高HIV病毒载量和低CD4计数；代谢异常，包括糖尿病，脂肪营养不良和高甘油三酸酯血症；以及炎症标记和内皮粘附分子，包括高敏CRP，E-选择蛋白和ICAM-1。这项调查将对艾滋病毒感染妇女预测，预防或扭转动脉粥样硬化的战略的发展具有重大影响。