Rationale and design of the Mechanistic Substudy of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE): Effects of pitavastatin on coronary artery disease and inflammatory biomarkers

Am Heart J. 2019 Jun;212:1-12. doi: 10.1016/j.ahj.2019.02.011. Epub 2019 Mar 4.


Background: People with HIV (PWH) have increased cardiovascular events, inflammation, and high-risk coronary atherosclerosis. Statin therapy has been shown to lower the risk of cardiovascular disease (CVD) in the general population, but whether this results from reductions in coronary atherosclerosis and is mediated by decreased inflammation remains unknown.

Methods: REPRIEVE is a randomized, placebo-controlled trial of pitavastatin calcium (4 mg/day) vs. placebo enrolling at least 7500 PWH between 40-75 years, on antiretroviral therapy (ART), with low to moderate traditional CVD risk. The Mechanistic Substudy of REPRIEVE (A5333s) is co-enrolling 800 participants from 31 US sites. These participants undergo serial contrast enhanced coronary computed tomography angiography (CCTA) and measurements of biomarkers of inflammation and immune activation at baseline and after 2 years of follow-up. The primary objectives are to determine the effects of pitavastatin on noncalcified coronary atherosclerotic plaque (NCP) volume, low attenuation plaque, and positive remodeling and on changes in immune activation and inflammation and to assess relationships between the two. Changes in CAD will be assessed in a standardized fashion by a core lab with expert readers blinded to time points and participant information; immune activation and inflammation assessment is also performed centrally.

Results: To date the Mechanistic Substudy has completed planned enrollment, with 805 participants.

Conclusion: This study represents the first large, randomized, CCTA-based assessment of the effects of a primary prevention strategy for CVD on high-risk CAD, immune activation and inflammation among PWH. The study will assess pitavastatin's effects on coronary plaque, and the interrelationship of these changes with biomarkers of immune activation and inflammation in PWH to determine mechanisms of CVD prevention and improved outcomes in this population.

Trial registration: ClinicalTrials.gov NCT02344290.

Publication types

  • Clinical Trial Protocol
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-HIV Agents / therapeutic use
  • Biomarkers / blood
  • Computed Tomography Angiography
  • Coronary Angiography
  • Coronary Artery Disease / complications*
  • Coronary Artery Disease / immunology
  • Coronary Artery Disease / prevention & control*
  • Double-Blind Method
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Inflammation / prevention & control*
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic / diagnostic imaging
  • Plaque, Atherosclerotic / prevention & control
  • Primary Prevention
  • Prospective Studies
  • Quinolines / therapeutic use*
  • Risk Factors


  • Anti-HIV Agents
  • Biomarkers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Quinolines
  • pitavastatin

Associated data

  • ClinicalTrials.gov/NCT02344290