Atherosclerosis and Inflammation in HIV Disease

描述（由申请人提供）： 由于使用抗逆转录病毒疗法，全世界艾滋病毒感染者的存活率显著提高。与HIV感染及其治疗相关的代谢和心血管并发症随着慢性病毒感染患者人群的年龄增长而变得越来越明显。HIV感染患者的代谢和炎症变化包括血脂异常、胰岛素抵抗、脂肪再分布伴脂肪细胞因子分泌异常、单核细胞亚群改变和T细胞活化可能增加动脉粥样硬化疾病的风险。拟议拨款的目的是：1）使用CT血管造影术确定HIV患者与年龄匹配的无HIV感染的对照受试者相比的亚临床冠状动脉粥样硬化的患病率和程度，2）检查HIV患者中冠状动脉粥样硬化的风险因素，特别是评估脂肪细胞因子、单核细胞亚群和T细胞活化在动脉粥样硬化发展中的潜在作用，和3）在患有亚临床冠状动脉粥样硬化的HIV患者中进行随机、安慰剂对照的生理学研究，比较他汀类药物治疗相对于安慰剂对斑块炎症（如通过18 F-氟脱氧葡萄糖正电子发射断层扫描测定的）、斑块进展抑制（如通过冠状动脉CT血管造影测定的）、单核细胞亚群和T细胞应答的作用。动脉粥样硬化疾病负担的表征以及与HIV中动脉粥样硬化疾病相关的危险因素的识别将有助于指导未来为HIV患者群体设计适当的预防和治疗策略。为了实现这些目标，候选人将由来自以患者为导向的转化研究，内分泌学，心脏病学，炎症生物学，HIV医学，心脏成像和生物统计学等多个相关学科的国际公认专家指导。他们的指导和候选人的机构支持的力量将提供一个非常适合的学术环境进行这项研究，并培养候选人的职业发展。这个K23职业发展奖将帮助候选人获得额外的研究技能，以实现她成为一个独立的以患者为导向的翻译研究者的目标。 (End摘要）

DESCRIPTION (provided by applicant): Survival of HIV-infected patients worldwide has remarkably improved with the use of anti-retroviral therapy. Metabolic and cardiovascular complications associated with HIV infection and its treatment are becoming more evident as this patient population ages with chronic viral infection. Metabolic and inflammatory changes in HIV-infected patients including dyslipidemia, insulin resistance, fat redistribution with abnormal adipocytokine secretion, alterations in monocyte subsets, and T-cell activation may increase the risk of atherosclerotic disease. The aims of the proposed grant are: 1) to determine the prevalence and degree of subclinical coronary atherosclerosis using CT angiography in patients with HIV compared to agematched control subjects without HIV infection, 2) to examine risk factors for coronary atherosclerosis in HIV patients, specifically evaluating the potential roles of adipocytokines, monocyte subsets, and T cell activation in atherosclerosis development, and 3) to perform a randomized, placebo-controlled, physiologic study in HIV patients with subclinical coronary atherosclerosis comparing the effects of statin therapy vs. placebo on plaque inflammation (as determined by 18F-fluorodeoxyglucose positron emission tomography), inhibition of plaque progression (as determined by coronary CT angiography), monocyte subsets and T cell response. Characterization of the atherosclerotic disease burden as well as identification of risk factors associated with atherosclerotic disease in HIV will be instrumental to guide the future design of appropriate prevention and treatment strategies for the HIV patient population. To achieve these aims, the candidate will be mentored by internationally recognized experts from several relevant disciplines in patient-oriented and translational research, endocrinology, cardiology, inflammation biology, HIV medicine, cardiac imaging, and biostatistics. Their mentorship and the strength of the candidate's institutional support will provide a well-suited academic environment to conduct this research and to nurture the candidate's career development. This K23 career development award will help the candidate to acquire the additional research skills to achieve her goal of becoming an independent patientoriented translational investigator. (End of Abstract)