1/2 REPRIEVE Extension for Trial Completion

项目摘要-摘要 在全球范围内，心血管疾病(CVD)的负担正在增加，并且是患有心脏病的人死亡的主要原因 HIV(威尔斯亲王医院)。然而，还没有关于有效的初级心血管疾病预防的大型试验的数据。 威尔斯亲王医院的策略。正在进行的缓刑试验将解决这一关键的知识差距，假设 他汀类药物对低密度脂蛋白、免疫激活和炎症途径具有多效性作用，将改变 威斯康星医院的传统和非传统风险和预防主要不良心血管事件(MACE)。 缓刑处于有利地位，可提供高质量、临床可操作和可推广的信息以进行转移 目前的艾滋病毒护理范例，与NHLBI和OAR的目标保持一致，以减少心血管疾病和改善 威尔斯亲王医院的整体健康状况。缓刑遇到了重大挑战，预计将进行大规模审判。7770 参与者(31%为女性，43%为黑人，25%为拉丁裔)来自12个国家的100多个地点， 可推广的人口。留存率很高，&gt；90%。终点(MACE)尽管处于低点，但仍在稳步积累 ASCVD风险评分中值为4.5%，与非传统风险导致心血管疾病的假设一致 爱滋病毒。机械学子研究已经达到了它的目标，招募了800多名参与者进行连续冠状动脉CT检查 血管造影(CTA)和免疫功能。子研究的初步基线数据支持我们的假设， 斑块与心血管疾病风险有关，但也独立于IL-6和LP-PLA2，免疫功能和 正在缓期治疗的动脉炎症。此外，正在利用缓刑来评估 他汀类药物对COVID严重性的影响，以及对PWH的长期影响，是该领域尚未回答的关键问题。 缓刑已经执行了6年多，从根本上说是强大的。然而，由于持续时间较长， 在新的指导方针下，对招募和方案进行修订，以确定最佳高危群体，中位数持续时间 随访时间仍然较短，仅为3.5年。缓刑需要额外的时间，预计为2年，外加结束 年，收集必要的MACE，以确保有足够的电力，分析和传播这些数据。压迫感 自缓刑启动以来，对一项大型全球初级预防试验的数据的需求才有所增加。 试验的完成将保护NIH初始投资的价值，并履行对我们的承诺 参与者和科学界，以达到试验的目标。此应用程序用于临床协调 试验完成缓期延期中心(CCC)侧重于临床理论基础和 协调审判。数据协调中心(DCC)应用侧重于数据管理， 包括机械学子研究的冠状动脉CTA数据，以及试验设计的统计理论基础。

Project Summary-Abstract Globally, cardiovascular disease (CVD) burden is increasing and a major cause of mortality among people with HIV (PWH). However, data are not yet available from large trials on an effective primary CVD prevention strategy for PWH. The ongoing REPRIEVE trial will address this critical knowledge gap, hypothesizing that statin therapy, with pleiotropic effects on LDL, immune activation and inflammatory pathways, will modify traditional and nontraditional risks and prevent major adverse cardiovascular events (MACE) in PWH. REPRIEVE is well-positioned to provide high quality, clinically actionable and generalizable information to shift the current paradigm of HIV care, in alignment with the goals of NHLBI and OAR to reduce CVD and improve the overall health of PWH. REPRIEVE has met major challenges, anticipated for a large trial. 7,770 participants (31% female, 43% Black, 25% Latino) were enrolled from over 100 sites in 12 countries, a diverse, generalizable population. Retention is high, >90%. Endpoint (MACE) are accumulating steadily despite a low median ASCVD risk score of 4.5%, consistent with the hypothesis that nontraditional risks contribute to CVD in HIV. The Mechanistic Substudy has met its goal, enrolling over 800 participants for serial coronary CT angiography (CTA) and immune function. Preliminary baseline data from the substudy support our hypothesis, linking plaque to CVD risk but also independently to IL-6 and Lp-PLA2, key indices of immune function and arterial inflammation that are being targeted in REPRIEVE. Moreover, REPRIEVE is being leveraged to assess statin effects on COVID severity, and long-term effects in PWH, critical unanswered questions for the field. REPRIEVE has executed well over 6 years and is fundamentally strong. However, with a long duration of recruitment and protocol revisions to identify the optimal at-risk group given new guidelines, median duration of follow up is still short at 3.5 years. REPRIEVE needs additional time, projected at 2 years, plus a close out year, to collect necessary MACE to ensure adequate power, analyze, and disseminate this data. The pressing need for data from a large global primary prevention trial has only grown since REPRIEVE was initiated. Completion of the trial will protect the value of the initial NIH investment and honor the commitment to our participants and scientific community to meet the Aims of the trial. This application for the Clinical Coordinating Center (CCC) of the REPRIEVE Extension for Trial Completion focuses on the clinical rationale and coordination of the trial. The Data Coordinating Center (DCC) application focuses on data management, including the coronary CTA data of the Mechanistic Substudy, and the statistical rationale for the trial design.