REPRIEVE - CCC - Lead Application

项目摘要 针对NOT-HL-20-757，特别利益通知(NOSI)：行政补编的供应 和关于2019年冠状病毒病的修订补充资料(新冠肺炎)和PA-18-591管理 美国国立卫生研究院现有拨款和合作协议的补编、所附的行政补编、 利用家长补助金U01 HL123336提交审议。了解与CoVID相关的简历 高危人群中的并发症是一个紧迫的国家优先事项。回溯性病例系列有 显示，在普通人群中使用新冠肺炎住院的患者中，约有20%至30% 有证据表明，心肌损伤与包括心脏功能障碍在内的不良后果有关， 心律失常、高凝状态和死亡。此外，有重要的证据表明内皮细胞和 与新冠肺炎相关的血管功能障碍，与血管紧张素转换酶-2或其他机制的膜摄取有关。 艾滋病毒携带者(PWH)已经面临着更高的心肌梗死和心力衰竭风险 普通民众。新冠肺炎如何影响重型肝炎患者的心血管发病率和死亡率仍不清楚 预防/治疗策略尚未确定。我们建议利用缓刑审判-- 专注于预防艾滋病毒相关心血管疾病的最大国际随机试验--以解决关键问题 威斯康星医院对SARS-CoV-2感染和COVID相关心血管并发症的认识差距。学习 7,700名年龄在40-75岁的PWH横跨五大洲，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和 有效地减轻血管炎症和改善内皮功能，补充的结果将 提供有关艾滋病毒和新冠肺炎的关键信息，反过来，提供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的影响，以及MACE。这些结果将是 可广泛推广到同时有新冠肺炎和心血管疾病风险的大量艾滋病毒患者和 也适用于其他有心血管疾病风险的人群，这些人群感染了冠状病毒。

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.