Inflammatory and Immune Mechanisms of Atherosclerosis in HIV-Infected Women

描述(由申请人提供)： 这项研究将检验免疫、炎症、凝血和血脂紊乱作为参与妇女机构间艾滋病毒研究(WIHS)的艾滋病毒感染妇女动脉粥样硬化增加的潜在介体。受试者将包括750名感染艾滋病毒的妇女和250名未感染艾滋病毒的妇女，他们参加了WIHS颈动脉超声研究的后续阶段。这套特定的目标包括两个主要目标：目标1专注于已建立的炎症和凝血生物标志物作为亚临床动脉粥样硬化的预测指标。目的2检查构成“经典”血管危险因素的血脂变化。数据分析目标是：(1)将炎症和凝血标记物的变化与艾滋病毒疾病的分期和治疗相关联，包括启动HAART以及病毒期和CD4+状态的变化；(2)确定免疫、炎症和凝血机制是否导致艾滋病毒感染妇女动脉粥样硬化的增加；(3)确定由于HAART和艾滋病毒疾病阶段的变化而导致的“经典”血管风险因素(如脂质)的变化，以及这对动脉粥样硬化的影响。此外，我们提出了三个探索性目标，以检测可能在HIV感染的成年人动脉粥样硬化中起重要作用的新的免疫和炎症介质：1.肠道微生物的移位，16S RNA测量；2.T细胞衰老(CD4+CD28-和CD8+CD28-T细胞)；3.T调节细胞。这项研究将检验免疫、炎症、凝血和血脂紊乱作为参与妇女机构间艾滋病毒研究(WIHS)的艾滋病毒感染妇女动脉粥样硬化增加的潜在介体。我们将(1)将炎症和凝血标志物的变化与HIV疾病的分期和治疗相关联，包括HAART的启动以及病毒症和CD4+状态的变化；(2)确定免疫、炎症和凝血机制是否导致艾滋病毒感染妇女动脉粥样硬化的增加；以及(3)确定由于HAART和HIV疾病阶段的变化而导致的“经典”血管风险因素(例如，脂质)的变化，以及这对动脉粥样硬化的影响。(摘要结束)

DESCRIPTION (provided by applicant): This investigation will examine immune, inflammatory, coagulation, and lipid disturbances as potential mediators of increased atherosclerosis in HIV-infected women participating in the Women's Interagency HIV Study (WIHS). Subjects will include 750 HIV-infected and 250 HIV-uninfected women participating in the Follow-up Phase of the WIHS Carotid Artery Ultrasound Study. The set of specific aims include two primary aims: Aim 1 focuses on established inflammation and coagulation biomarkers as predictors of subclinical atherosclerosis. Aim 2 examines lipid changes which constitute "classic" vascular risk factors. Data analysis goals are: (1) To correlate changes in inflammatory and coagulation markers with HIV disease stage and treatments, including initiation of HAART and changes in viremic and CD4+ status; (2) To determine if immune, inflammatory, and coagulation mechanisms contribute to increased atherosclerosis in HIV-infected women; (3) To determine changes in "classic" vascular risk factors (e.g., lipids) over time due to changes in HAART and HIV disease stage, and how this impacts atherosclerosis. In addition, we propose three exploratory aims examining novel immune and inflammatory mediators that may be of importance to atherosclerosis in HIV-infected adults: 1. Translocation of gut microbes, as measured by 16s RNA; 2. T-cell senescence (CD4+CD28- and CD8+CD28- T-cells); 3. T regulatory cells. This investigation will examine immune, inflammatory, coagulation, and lipid disturbances as potential mediators of increased atherosclerosis in HIV-infected women participating in the Women's Interagency HIV Study (WIHS). We will (1) correlate changes in inflammatory and coagulation markers with HIV disease stage and treatments, including initiation of HAART and changes in viremic and CD4+ status; (2) determine if immune, inflammatory, and coagulation mechanisms contribute to increased atherosclerosis in HIV-infected women; and (3) determine changes in "classic" vascular risk factors (e.g., lipids) over time due to changes in HAART and HIV disease stage, and how this impacts atherosclerosis. (End of Abstract)