Mechanisms of Atherosclerosis and CVD in HIV+ Women

描述（由申请人提供）：由于在高效抗逆转录病毒治疗（HAART）时代，HIV感染者的生存率显著提高，因此阐明HIV感染及其治疗的长期影响越来越重要。大量数据表明，艾滋病毒感染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答案。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作用可能会促进动脉粥样硬化，或者这些药物也可能直接影响血管。HIV脂肪营养不良综合征，无论是由于药物或HIV本身，也可能是一个促成因素。关于HIV感染中炎症标志物持续升高的潜在致动脉粥样硬化作用知之甚少。此外，在艾滋病毒感染的动脉粥样硬化和心血管疾病研究中，妇女、非洲裔美国人和西班牙裔美国人的代表性不足。本研究的总体目标是评估HIV感染妇女是否加速动脉粥样硬化，并确定HIV感染中动脉粥样硬化的潜在介质。在妇女跨部门艾滋病研究（WIHS）队列中，本研究将使用B型超声成像方法评估亚临床动脉粥样硬化的进展，以测量颈动脉内膜中层厚度（IMT）随时间的变化。这项研究将包括250名感染艾滋病毒的妇女和250名艾滋病毒阴性对照，在六个WIHS诊所。将在48个月内每年进行一次颈动脉超声检查，IMT进展率将由核心成像机构集中解读。广泛的WIHS数据库，包括每6个月研究访视时收集的数据，将用于评估IMT进展是否与HIV感染有关; HAART、Pis或其他抗逆转录病毒药物的使用; AIDS的发生、高HIV病毒载量和低CD 4计数;代谢异常，包括糖尿病、脂肪代谢障碍和高脂血症;以及炎症标志物和内皮粘附分子，包括高敏CRP、E-选择素和ICAM-1。这项研究将对发展预测、预防或逆转HIV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.