Fat Redistribution and Metabolic Change in HIV Infection

描述(由申请人提供)：由于引入HIV蛋白酶抑制剂(PI)导致脂肪分布以及脂肪和葡萄糖代谢的变化，越来越多的人关注艾滋病毒感染(HIV+)患者中的心血管疾病(CVD)流行。然而，对于PI的作用存在争议。来自HIV感染中脂肪重新分布和代谢变化(FRAM)的研究数据预测心血管疾病增加，但PI药物不是主要危险因素。我们发现，其他ARV和HIV本身也会导致脂肪分布和代谢的异常。吸烟和HIV+患者的微量蛋白尿也会增加患心血管疾病的风险。关键是要确定动脉粥样硬化是否在HIV+患者中增加，如果是的话，确定致病因素。FRAM特别适合于检查动脉粥样硬化的因素，因为从地理和种族不同的人群中随机选择了大量艾滋病毒感染的男性和女性，以及CARDIA研究子集中匹配良好的对照组，使用相同的严格方案进行研究。我们评估了区域脂肪量、传统代谢危险因素、血压、家族病史和习惯。我们建议通过超声测量颈动脉内膜中层厚度(IMT)来确定动脉粥样硬化的患病率及其影响因素。我们将重复MRI的身体成分、DXA的血压、骨密度和习惯调查，以及传统代谢(如葡萄糖和脂肪)和新型炎症(如CRP、细胞因子)心血管危险因素的实验室。将进行葡萄糖耐量和脂肪清除。所有研究都将在上次FRAM检查的受试者中进行，但我们也会将IMT、实验室结果、血压和习惯与更大的CARDIA和MESA队列进行比较。利用多元逐步Logistic回归分析，我们将评估IMT导致的动脉粥样硬化与HIV非独立危险因素的关系，如吸烟，在HIV+队列中可能增加，以及HIV影响的危险因素(例如，糖脂代谢，炎症)。我们将评估HIV、ARV和脂肪分布的变化与心血管疾病危险因素和IMT的关系。这些结果将提供有关动脉粥样硬化风险及其影响因素的基本信息，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.