Metabolic Complications of HIV and Responses to Pioglitazone

描述(由申请人提供)：本申请的总体目标是支持首席研究人员努力发展职业生涯，开展以患者为中心的高水平研究，重点关注抗逆转录病毒治疗的代谢毒性。为了实现这一目标，一个有指导意义的、科学的培训计划是。拟议中包括通过凯斯西储大学(CWRU)临床研究学者计划(CRSP)进行的教学培训，以及CWRU克利夫兰临床勒纳医学院(CCLCM)医学教育和研究发展中心(CMERAD)计划的课程工作，由艾滋病毒、代谢和心血管疾病领域的专家组成的指导和科学咨询委员会已经成立，以协助首席研究员在以患者为导向的研究中建立职业生涯。她将得到克利夫兰诊所卓越的研究环境的全力支持。这项应用的主要目标是通过评估改善脂肪萎缩和亚临床动脉粥样硬化的策略来减少与艾滋病毒和抗逆转录病毒治疗(ART)相关的代谢毒性相关的发病率。为了实现这些目标，这项应用有以下具体目的：1)评估吡格列酮对接受胸腺嘧啶核苷保留疗法治疗的HIV感染的脂肪萎缩患者的肢体脂肪和脂肪线粒体DNA的疗效；2)评估吡格列酮对代谢综合征和潜在的动脉粥样硬化的疗效。这些假设将通过一项为期48周的前瞻性、随机、安慰剂对照试验进行检验。有效的抗逆转录病毒治疗的长期后果，包括脂代谢紊乱、胰岛素抵抗和动脉粥样硬化疾病的代谢并发症，已成为这种挽救生命的治疗的主要潜在限制。随着发展中国家更多的艾滋病毒感染者获得抗逆转录病毒治疗，与抗逆转录病毒治疗有关的代谢并发症未来也可能产生越来越大的全球影响。

DESCRIPTION (provided by applicant): The overall goal of this application is to support the Principal Investigator's efforts in developing a career performing high-caliber patient-oriented research focusing on the metabolic toxicities of antiretroviral therapy. To accomplish this goal, a mentored program of didactic and scientific training is. proposed which includes didactic training through the Clinical Research Scholars Program (CRSP) at Case Western Reserve University (CWRU) and coursework that is part of the Center for Medical Education and Research Development (CMERAD) Program at the Cleveland Clinic Lerner College of Medicine (CCLCM) of CWRU, mentoring and scientific advisory committee consisting of experts in the areas of HIV and metabolic and cardiovascular diseases has been assembled to assist the principal investigator in her efforts to establish a career in patient-oriented research. She will have the full support of the Cleveland Clinic's outstanding research environment. The primary goal of this application is to decrease the morbidity associated with HIV and antiretroviral therapy (ART)-associated metabolic toxicities by evaluating strategies to improve lipoatrophy and subclinical atherosclerosis. To meet these goals, this application has the following specific aims: 1) Evaluate the efficacy of pioglitazone on limb fat and fat mitochondrial DNA in HIV-infected subjects with lipoatrophy treated with thymidine-sparing regimens 2) Evaluate the efficacy of pioglitazone on the metabolic syndrome and underlying atherosclerosis. The hypotheses will be tested using a 48-week prospective, randomized, placebo-controlled trial. Long-term consequences of potent antiretroviral therapy including the metabolic complications of lipodystropohy, insulin resistance and atherosclerotic disease have emerged as a major potential limitation to this life-saving treatment. HIV-related metabolic complications to ART are also likely to have a future increasing global impact as more HIV-infected persons in developing countries gain access to ART.