Mechanisms of Atherosclerosis and CVD in HIV+ Women

描述(申请人提供)：在高效抗逆转录病毒疗法(HAART)的时代，艾滋病毒感染者的存活率显著提高，澄清艾滋病毒感染及其治疗的长期影响变得越来越重要。大量数据表明，艾滋病毒感染患者有过早的动脉粥样硬化和心血管事件。然而，关于这些发现的因果机制和临床相关性的几个主要问题仍然没有得到回答。动脉粥样硬化可能是由于艾滋病毒感染，使用抗逆转录病毒药物，或两者兼而有之。众所周知，蛋白酶抑制剂(Pis)或其他抗逆转录病毒药物的代谢效应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效应。艾滋病毒脂营养不良综合征，无论是由于药物或艾滋病毒本身，也可能是一个促成因素。在HIV感染中，炎症标志物的持续升高对动脉粥样硬化的潜在影响知之甚少。此外，女性、非裔美国人和拉美裔美国人在艾滋病毒感染中动脉粥样硬化和心血管疾病的研究中代表性不足。这项调查的总体目标是评估感染艾滋病毒的妇女是否加速了动脉粥样硬化，并确定在艾滋病毒感染中动脉粥样硬化的潜在介体。在女性机构间艾滋病毒研究(WIHS)队列中，这项研究将使用B型超声成像方法来评估亚临床动脉粥样硬化的进展，以测量颈动脉内膜-中层厚度(IMT)随时间的变化。这项研究将包括WIHS六个诊所的250名艾滋病毒感染妇女和250名艾滋病毒阴性对照。颈动脉超声将在48个月内每隔一年进行一次，IMT进展速度将在核心成像设备中进行集中解释。WIHS广泛的数据库包括每六个月进行一次研究访问时收集的数据，将用于评估IMT进展是否与HIV感染有关；使用HAART、Pis或其他抗逆转录病毒药物；艾滋病的发生、HIV病毒载量高和CD4计数低；代谢异常，包括糖尿病、脂肪营养不良和高甘油三酯血症；以及炎症标志物和内皮黏附分子，包括高敏CRP、E-选择素和ICAM-1。这项研究将对制定预测、预防或逆转艾滋病毒感染妇女动脉粥样硬化的策略具有重要意义。

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.