Rationale and design of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE)

Abstract

Background: Cardiovascular disease (CVD) is more frequent among people with HIV (PWH) and may relate to traditional and nontraditional factors, including inflammation and immune activation. A critical need exists to develop effective strategies to prevent CVD in this population.

Methods: The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) (A5332) is a prospective, randomized, placebo-controlled trial of a statin strategy for the primary prevention of major adverse cardiovascular events (MACE) in PWH with low to moderate traditional risk. At least 7,500 PWH, 40-75 years of age, on stable antiretroviral therapy, will be randomized to pitavastatin calcium (4 mg/d) or identical placebo and followed for up to 8 years. Participants are enrolled based on the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) atherosclerotic cardiovascular disease (ASCVD) risk score and low-density lipoprotein cholesterol (LDL-C) level with a goal to identify a low- to moderate-risk population who might benefit from a pharmacologic CVD prevention strategy. Potential participants with a risk score ≤ 15% were eligible based on decreasing LDL-C thresholds for increasing risk score >7.5% (LDL-C <190 mg/dL for risk score <7.5%, LDL-C <160 mg/dL for risk score 7.6%-10%, and LDL-C<130 mg/dL for risk score 10.1%-15%). The primary objective is to determine effects on a composite end point of MACE. Formal and independent adjudication of clinical events will occur using standardized criteria. Key secondary end points include effects on MACE components, all-cause mortality, specified non-CVD events, AIDS and non-AIDS events, and safety.

Results: To date, REPRIEVE has enrolled >7,500 participants at approximately 120 sites across 11 countries, generating a diverse and representative population of PWH to investigate the primary objective of the trial.

Conclusions: REPRIEVE is the first trial investigating a primary CVD prevention strategy in PWH. REPRIEVE will inform the field of the efficacy and safety of a statin strategy among HIV-infected participants on antiretroviral therapy and provide critical information on CVD mechanisms and non-CVD events in PWH.

Trial registration: ClinicalTrials.gov NCT02344290.

Figure 1.

REPRIEVE Trial Schema

Figure 2.

Flow Diagram of REPRIEVE Study Visits

Figure 3.. REPRIEVE Trial Accrual Figure.

Dotted line shows actual accrual progress. Colored bands denote predefined NIH target enrollment zones: yellow/light gray (100% to 75%), orange/medium gray (75% to 25%), red/dark gray (<25%).

Figure 4.

Timeline of REPRIEVE Design Changes and Amendments

Figure 5.

REPRIEVE Trial Organization