Effects of HIV antiretroviral therapy on pulmomary function in a randomized trial

随机试验中 HIV 抗逆转录病毒治疗对肺功能的影响

• 批准号: 8318667
• 负责人: KEN M. KUNISAKI
• 金额: $ 50.39万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-20 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8318667
• 关键词: Address; Ancillary Study; Anti-Retroviral Agents; Award; Biological; Biological Markers; CD4 Lymphocyte Count; Cells; Chronic; Chronic Obstructive Airway Disease; Clinical; Data; Data Sources; Databases; Development; Early treatment; Enrollment; Evaluation; Forced expiratory volume function; Future; Genetic; Genomics; Grant; HIV; HIV-1; Health; Health Status; International; International Network for Strategic Initiatives in Global HIV Trials; Investigation; Knowledge; Leadership; Lung; Lung Inflammation; Measurement; Measures; Modeling; National Institute of Allergy and Infectious Disease; Outcome; Parents; Participant; Pathogenesis; Patients; Persons; Proteomics; Pulmonary Function Test/Forced Expiratory Volume 1; Questionnaires; Randomized; Randomized Controlled Trials; Relative (related person); Reporting; Research Design; Research Infrastructure; Research Proposals; Respiratory Tract Infections; Respiratory physiology; Risk; Schedule; Smoker; Smoking Status; Specimen; Time; Treatment Protocols; Virus Diseases; abstracting; antiretroviral therapy; cost; design; experience; follow-up; innovation; non-smoker; pulmonary function; randomized trial; repository; research study; respiratory; treatment trial; viral RNA

DESCRIPTION (provided by applicant): Multiple data sources suggest that patients infected with human immunodeficiency virus (HIV) experience chronic lung inflammation, rapid lung function decline, and an increased risk of chronic obstructive pulmonary disease (COPD). Although newer and more potent antiretroviral treatment (ART) appears to nearly eliminate lung inflammation, ART's effects on the rate of lung function decline and other important clinical outcomes remain unknown. Our proposal is designed to address this knowledge gap, while providing a better understanding of the mechanisms for the rapid lung function decline observed in patients with HIV infection. We will accomplish these general aims through longitudinal measurements of pulmonary function and respiratory health status in a subsample of 1,000 participants enrolled in a large, international, randomized, controlled trial - the Strategic Timing of Antiretroviral Treatment (START) trial. START is scheduled to begin in early 2009. The parent trial will enroll 4,000 HIV-1 (subsequently referred to as HIV) infected persons who are na¿ve to antiretroviral treatment, with a CD4+ count >500 cells/mm3. Participants will be randomized to either immediate initiation of potent ART or deferral of ART until the CD4+ count declines to <350 cells/mm3. This permits an appropriately controlled, randomized experimental evaluation of the relative effects of early ART treatment (vs. deferred treatment) on pulmonary status in patients with HIV infection. Much of the infrastructure for the START trial is supported by the National Institute of Allergy and Infectious Diseases (NIAID) through a Leadership Group grant award to the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT). Our proposal seeks support to include the measurement of pulmonary function and respiratory health status in an ancillary study to START. With the data being collected by the main START protocol and the additional data we propose to collect as part of this application, respiratory parameters will be reliably quantified in HIV-infected patients treated with immediate and deferred ART, with control of multiple confounding factors through randomization. The extensive biological specimen repository, including genetic data and other data collected as part of the main START protocol, will provide opportunities for multiple future investigations of biomarkers, proteomics, and genomics related to the development of COPD in patients infected with HIV. Our study will advance understanding of the pathogenesis and course of rapid lung function decline and subsequent COPD in the presence of HIV infection.

描述（由适用提供）：多个数据来源表明，感染人类免疫缺陷病毒（HIV）的患者经历了慢性肺部感染，快速肺功能下降以及慢性阻塞性肺疾病（COPD）的风险增加。尽管较新的，更多的潜在抗逆转录病毒治疗（ART）似乎几乎消除了肺部感染，但艺术对肺功能下降速度的影响和其他重要的临床结果仍然未知。我们的建议旨在解决这一知识差距，同时更好地了解HIV感染患者观察到的快速肺功能下降机制。我们将通过在1,000名参与者的子样本中纵向测量肺功能和呼吸健康状况的纵向测量来实现这些总体目标，该子样本是参加了大型，国际，随机，对照试验的参与者 - 抗逆转录病毒治疗（Start）试验的战略时机。 Start计划于2009年初开始。父母试验将招募4,000名HIV-1（随后称为HIV）受感染的人，他们是抗逆转录病毒治疗，CD4+计数> 500细胞/mm3。参与者将被随机分配给潜在艺术的立即主动性，或者是ART的延期，直到CD4+计数下降到<350个细胞/mm3。这允许对早期艺术治疗（与递延治疗）对HIV感染患者的肺状况的相对影响进行适当控制，随机的实验评估。开始审判的大部分基础设施得到了美国国家过敏和传染病研究所（NIAID）的支持，这是通过为全球HIV试验（Insight）国际战略倡议的领导力小组授予奖励奖。我们的建议寻求支持，以在一项辅助研究中开始包括肺功能的测量和呼吸健康状况。随着主要开始方案收集的数据以及我们提出的其他数据作为本应用程序的一部分，将在接受直接和递延ART治疗的HIV感染患者中可靠地量化呼吸参数，并通过随机化控制多个混杂因素。广泛的生物标本存储库，包括遗传数据和作为主要开始方案的一部分收集的其他数据，将为与HIV感染的患者的COPD发展有关的生物标志物，蛋白质组学和基因组学的多种投资提供机会。我们的研究将在HIV感染的存在下提高人们对快速肺功能下降的发病机理和随后的COPD的了解。