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.