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 7500 PWH, 40-75yrs of age, on stable antiretroviral therapy (ART), will be randomized to pitavastatin calcium (4 mg/day) or identical placebo and followed for up to 7 years. Participants are enrolled based on the 2013 ACC/AHA ASCVD risk score and LDL 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 endpoint of MACE. Formal and independent adjudication of clinical events will occur utilizing standardized criteria. Key secondary endpoints 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 over 7300 participants, at approximately 120 sites across 11 countries, generating a diverse and representative population of PWH, to investigate the primary objective of the trial. Conclusion-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 HIVinfected participants on ART and provide critical information on CVD mechanisms and non-CVD events in PWH. Grinspoon et al.

Cardiovascular morbidity and mortality among persons diagnosed with tuberculosis: A systematic review and meta-analysis

“…In TB medicine, statins have potential for improving TB treatment outcomes [ 58 ], and are being considered as host-directed therapy in two trials where they are used as adjuvants to TB chemotherapy [ 59 – 61 ]. While not designed to assess the efficacy of statins for CVD prevention in TB patients, dose-safety data from these trials may inform future trials for TB patients with such a goal, similar, perhaps, to the REPRIEVE trial for HIV patients [ 57 ]. In the absence of RCT evidence of statin efficacy for CVD prevention in TB, a subgroup analysis of people with a history of TB within the REPRIEVE trial might provide estimates of statins’ effectiveness for reducing CVD risk in people living with HIV with a history of TB.…”

“…A scientific statement was recently issued by the American Heart Association reviewing the mounting evidence for the risk of CVD, as well as prevention and management strategies, for people living with HIV [56]. In this statement, the REPRIEVE trial for vascular event prevention among people living with HIV is mentioned for its potential to provide the first RCT evidence of statins' efficacy in CVD prevention among people living with HIV [57].…”

Measures of Adipose Tissue Redistribution and Atherosclerotic Coronary Plaque in HIV

“…Although studies in the non‐HIV population show that CAC score derived from cardiac CT is a clinical predictive marker of subclinical atherosclerosis and future CVD events , the impact of calcified plaque on CVD in PWH remains unclear. No studies to date have examined the role of calcified plaque or CAC score on predicting CVD events in HIV, and this will be addressed for the first time in the ongoing Randomized Trial to Prevent Vascular Events in HIV trial .…”

Effects of Integrase Inhibitor–Based ART on the NLRP3 Inflammasome Among ART-Naïve People With HIV

“…Select statins, such as atorvastatin, have been shown to reduce NLRP3 inflammasome activation in the general population [ 20 ] and thus may serve to reduce residual NLRP3 inflammasome activation among PWH on ART. The ongoing 7700-participant Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) [ 21 , 22 ] will demonstrate whether statin therapy affords ART-treated PWH cardio-protection via effects to dampen key indices of systemic immune activation—including those triggered by NLRP3 inflammasome activation.…”