Metabolic Complications of HIV and Responses to Pioglitazone

HIV 的代谢并发症和吡格列酮的反应

• 批准号: 7883345
• 负责人: Marisa Tungsiripat
• 金额: $ 12.91万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7883345
• 关键词: 2,4-thiazolidinedione; Acquired Immunodeficiency Syndrome; Adherence; Adipose tissue; Adverse effects; Advisory Committees; Agonist; Area; Atherosclerosis; Biological Markers; Body fat; Buttocks; Caliber; Cardiovascular Diseases; Cardiovascular system; Clinic; Clinical; Clinical Research; Complication; Coronary Arteriosclerosis; DEXA; Developing Countries; Development; Disease; Down-Regulation; Dyslipidemias; Environment; Exposure to; Face; Fatty acid glycerol esters; Future; Goals; HIV; Individual; Insulin Resistance; Intervention; Leg; Life; Limb structure; Link; Lipids; Lipoatrophy; Medical Education; Medicine; Mentors; Metabolic; Metabolic syndrome; Mitochondria; Mitochondrial DNA; Morbidity - disease rate; NCI Scholars Program; Nucleosides; PPAR gamma; Patients; Persons; Pharmaceutical Preparations; Pioglitazone; Placebos; Polymerase; Principal Investigator; Quality of life; Regimen; Research; Research Personnel; Reverse Transcriptase Inhibitors; Role; Scanning; Stavudine; Surrogate Markers; Tenofovir; Testing; Thiazolidinediones; Thymidine; Time; Toxic effect; Training; Universities; Zidovudine; abacavir; analog; antiretroviral therapy; arm; cardiovascular risk factor; career; college; diabetic; improved; inflammatory marker; mRNA Expression; meetings; mitochondrial dysfunction; mortality; nucleoside analog; patient oriented research; programs; prospective; randomized placebo controlled trial; research and development; response; rosiglitazone; subcutaneous; viral resistance; wasting

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.

描述（由申请人提供）：本申请的总体目标是支持主要研究者努力发展职业生涯，从事高素质的以患者为导向的研究，重点是抗逆转录病毒治疗的代谢毒性。为了实现这一目标，一个教学和科学培训的指导计划。建议包括通过凯斯西储大学（CWRU）的临床研究学者计划（CRSP）进行教学培训，以及CWRU克利夫兰诊所勒纳医学院（CCLCM）医学教育和研究发展中心（CMERAD）计划的一部分课程，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，以协助在她的努力，以建立一个以病人为导向的研究事业的首席研究员。她将得到克利夫兰诊所出色的研究环境的全力支持。本申请的主要目的是通过评估改善脂肪萎缩和亚临床动脉粥样硬化的策略，降低与HIV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，本申请具有以下具体目的：1）评价吡格列酮对用胸腺嘧啶保留方案治疗的患有脂肪萎缩的HIV感染受试者的肢体脂肪和脂肪线粒体DNA的功效2）评价吡格列酮对代谢综合征和潜在动脉粥样硬化的功效。将使用一项为期48周的前瞻性、随机化、安慰剂对照试验来检验假设。强效抗逆转录病毒治疗的长期后果，包括脂肪代谢障碍、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治疗的主要潜在限制。随着发展中国家越来越多的艾滋病毒感染者获得抗逆转录病毒疗法，抗逆转录病毒疗法的艾滋病毒相关代谢并发症今后也可能产生越来越大的全球影响。