REPRIEVE - CCC - Lead Application

项目摘要 针对NOT-HL-20-757，特别关注通知（NOSI）：管理补充材料的可用性 2019年冠状病毒病（COVID-19）和PA-18-591补充修订 现有NIH赠款和合作协议的补充，随附的行政补充， 利用母公司赠款U 01 HL 123336，提交审议。了解COVID相关简历 高危人群的并发症是国家的一个紧迫优先事项。回顾性病例系列包括 显示，在因COVID-19住院的普通人群中，约20%至30%的患者 心肌损伤的证据，与包括心功能障碍在内的不良结局相关， 心律失常、高凝事件和死亡。此外，有显著证据表明， 与COVID-19相关的血管功能障碍，与通过ACE-2或其他机制的膜摄取相关。 艾滋病毒感染者（PWH）已经面临心肌梗死和心力衰竭的风险增加， 普通民众。COVID-19如何影响威尔斯亲王医院的心血管发病率和死亡率仍不清楚， 预防/治疗战略尚未确定。我们建议利用REPRIEVE试验- 最大的国际随机试验，重点是预防HIV相关CV疾病-以解决关键的 威尔斯亲王医院对SARS-CoV-2感染和COVID相关CV并发症的知识差距。研究 来自五大洲的7，700名40-75岁的PWH，我们将专注于三个相互关联但独立的关键主题： 流行病学、宿主因素和保护策略。在这方面，他汀类药物具有多效性作用， 有效地减少血管炎症和改善内皮功能，补充的结果将 提供关于艾滋病毒和COVID-19的关键信息，以及他汀类药物的关键作用，以减轻 SARS-Co-V2病毒对心血管疾病和内皮功能以及MACE的影响。这些结果将 可广泛推广至同时存在COVID-19和CVD风险的大量HIV患者人群， 也适用于经历COVID感染的其他CVD风险人群。

Project Summary In response to NOT-HL-20-757, Notice of Special Interest (NOSI): Availability of Administrative Supplements and revision Supplements on Coronavirus Disease 2019 (COVID-19), and PA-18-591 Administrative Supplements for existing NIH Grants and Cooperative Agreements, the enclosed administrative supplement, leveraging parent grant U01 HL123336, is submitted for consideration. Understanding COVID-related CV complications in at-risk populations represents an urgent national priority. Retrospective case series have shown that among patients in the general population hospitalized with COVID-19, approximately 20 to 30% evidence myocardial injury, which is associated with adverse outcomes including cardiac dysfunction, arrythmia, hypercoagulable events, and death. In addition, significant evidence exists for endothelial and vascular dysfunction related to COVID-19, related to membrane uptake via ACE-2 or other mechanisms. People with HIV (PWH) already face increased risk of myocardial infarction and heart failure as compared with the general population. How COVID-19 affects CV morbidity and mortality among PWH remains unknown and preventive/therapeutic strategies have yet to be identified. We propose to leverage the REPRIEVE trial – the largest international randomized trial focused on preventing HIV-associated CV disease – to address critical knowledge gaps regarding SARS-CoV-2 infection and COVID-related CV complications among PWH. Studying 7,700 PWH ages 40-75 across 5 continents, we will focus on three interrelated but independent key topics: epidemiology, host factors, and protective strategies. In this regard, statins have pleiotropic effects and potently reduce vascular inflammation and improve endothelial function, The results of the supplement will provide critical information on HIV and COVID-19, and conversely critical effects of statins to mitigate effects of the SARS-Co-V2 virus on cardiovascular disease and endothelial function, and MACE. These results will be broadly generalizable to the large population of HIV patients simultaneously at risk for COVID-19 and CVD and also to other populations at risk for CVD experiencing COVID infection.