Fat Redistribution and Metabolic Change in HIV Infection

描述（由申请方提供）：由于引入HIV蛋白酶抑制剂（PI）后出现的脂肪分布以及脂质和葡萄糖代谢的变化，对HIV感染（HIV+）患者中心血管疾病（CVD）流行的担忧日益增加。然而，关于PI的作用存在争议。来自HIV感染的脂肪再分布和代谢变化（弗拉姆）研究的数据预测CVD增加，但PI药物不是主要的风险因素。我们发现，其他抗逆转录病毒和艾滋病毒本身有助于脂肪分布和代谢异常。吸烟和HIV+患者的微量白蛋白尿也会增加CVD风险。确定动脉粥样硬化是否在HIV+中增加是至关重要的，如果是这样，则定义贡献者。弗拉姆是唯一适合于检查动脉粥样硬化的贡献者，因为大量随机选择的HIV感染的男性和女性，从地理和种族不同的人群，以及良好匹配的对照组，从一个子集的心脏研究进行了研究相同的严格协议。我们评估了局部脂肪体积、传统代谢危险因素、血压、家族史和习惯。我们建议随访超声测量颈动脉内膜中层厚度（IMT），以确定动脉粥样硬化的患病率和影响因素。我们将通过MRI、血压、DXA骨密度和习惯调查重复身体成分，加上传统代谢实验室（例如，葡萄糖和脂质）和新的炎性（例如，CRP、细胞因子）CVD危险因素。将进行葡萄糖耐量和脂肪清除。所有研究都将在最后一次弗拉姆检查的受试者中进行，但我们还将比较IMT、实验室结果、血压和习惯与较大的CARDIA和梅萨队列。使用多变量逐步logistic回归分析，我们将评估IMT与HIV独立风险因素（如HIV+队列中可能增加的吸烟）和HIV影响的风险因素（例如，葡萄糖和脂质代谢、炎症）。我们将评估HIV、ARV和脂肪分布变化与CVD危险因素和IMT的关系。这些结果将提供有关动脉粥样硬化风险及其贡献者的重要信息，以帮助患者护理，政策和未来的研究。

DESCRIPTION (provided by applicant): There is increasing concern over an epidemic of cardiovascular disease (CVD) in patients with HIV infection (HIV+), due to changes in fat distribution and lipid and glucose metabolism that appeared with the introduction of HIV protease inhibitors (PI). However, there is controversy over the role of PI. Data from the study of Fat Redistribution And Metabolic Change in HIV Infection (FRAM) predict increased CVD, but PI drugs are not the major risk factor. We found that other ARV and HIV itself contribute to abnormalities in fat distribution and metabolism. Smoking and microalbuminuria in HIV+ also contribute to CVD risk. It is crucial to determine whether atherosclerosis is increased in HIV+ and, if so, to define the contributors. FRAM is uniquely suited to examine the contributors to atherosclerosis in that a large number of randomly selected HIV-infected men and women from geographic and ethnically diverse populations, and well matched controls from a subset of the CARDIA study were studied with the same rigorous protocol. We assessed regional fat volumes, traditional metabolic risk factors, blood pressure, family history and habits. We propose a follow up to measure carotid intimal medial thickness (IMT) by ultrasound to determine the prevalence of atherosclerosis and contributing factors. We will repeat body composition by MRI, blood pressure, bone density by DXA, and habit survey, plus laboratories for traditional metabolic (e.g., glucose and lipid) and novel inflammatory (e.g., CRP, cytokines) CVD risk factors. Glucose tolerance and fat clearance will be performed. All studies will be done in the subjects from the last FRAM exam, but we will also compare IMT, laboratory results, blood pressure and habits to the larger CARDIA and MESA cohorts. Using multivariate step-wise logistic regression analysis we will assess the association of atherosclerosis by IMT with HIV independent risk factors such as smoking that may be increased in HIV+ cohorts and HIV influenced risk factors (e.g., glucose and lipid metabolism, inflammation). We will assess the association of HIV, ARV and the changes in fat distribution with the CVD risk factors and with IMT. The results will provide essential information on the risk of atherosclerosis and its contributors to aid in patient care, policy and future research.