2/2 REPRIEVE Extension for Trial Completion

项目总结/文摘

Project Summary/Abstract This proposal will support the Data Coordinating Center (DCC) for the Randomized Trial to Prevent Vascular Events in HIV Trial (REPRIEVE) Extension for up to two additional years, with an additional year for study close-out. This additional time is necessary to collect the major adverse cardiovascular events (MACE) required to ensure adequate power to address the primary aim of REPRIEVE, to determine the efficacy of statins as a primary cardiovascular prevention strategy in HIV. Completion of the trial will protect the value of the initial NIH investment and leverage existing REPRIEVE infrastructure, with its data analytical and oversight structures. This DCC proposal is a companion to the REPRIEVE Clinical Coordinating Center (CCC) proposal. REPRIEVE is a multicenter, randomized, placebo controlled, pragmatic trial investigating the efficacy of statins for primary prevention of cardiovascular disease (CVD) events (primary endpoint) in 7,770 persons with HIV (PWH) without known CVD and with low to moderate CVD risk as per the 2013 ACC/AHA Pooled Cohort Equations, (referred to as ASCVD risk). To understand the biology of statin effects, 805 participants were co- enrolled in an embedded mechanistic substudy that will determine the effects of statins on non-calcified plaque volume and high risk plaque morphology using coronary computed tomographic angiography (CTA), as well as on blood biomarkers of vascular inflammation and immune activation after 4 months and two years. Further, in response to the global SARS-CoV-2 pandemic, REPRIEVE will address critical knowledge gaps regarding the epidemiology of SARS-CoV-2 infection and COVID-related CVD complications among PWH, and determine the protective statin effects for COVID disease across the globe. In the proposed extension, the REPRIEVE DCC will continue to provide methodological and logistical support for the collection, quality control, and analysis of data including rigorous, timely, and independent adjudication of potential MACE events. Furthermore, the DCC remains responsible for statistical design and analysis, assistance in protocol development, data management, CTA data acquisition and interpretation, biospecimen analysis, and electronic communications.