Evaluating the Use of Pitavastatin to Reduce the Risk of Cardiovascular Disease in HIV-Infected Adults
Condition: HIV Infections; Cardiovascular Diseases
MeSH terms: Cardiovascular Diseases
Study type: Interventional
Phase: Phase 3

Summary: 
      People infected with HIV are at risk for cardiovascular disease (CVD). This study will
      evaluate the use of pitavastatin to reduce the risk of CVD in adults infected with HIV who
      are on antiretroviral therapy (ART).

      The REPRIEVE trial consists of two parallel identical protocols:

        -  REPRIEVE (A5332) is funded by the NHLBI, with additional infrastructure support provided
           by the NIAID, and is conducted in U.S and select international sites (approximately 120
           sites in 11 countries).

        -  REPRIEVE (EU5332) is co-sponsored by NEAT ID and MGH, and is conducted at 13 sites in
           Spain.
    

Detailed description: 
      Currently, there are few strategies to prevent CVD in HIV-infected people, even though they
      are at high risk for developing CVD. Statin medications are used to lower cholesterol and may
      be effective at reducing the risk of CVD in people infected with HIV. The purpose of this
      study is to evaluate the use of pitavastatin to reduce the risk of CVD in adults infected
      with HIV who are on ART.

      This study will enroll adults infected with HIV who are on any ART regimen (ART is not
      provided by the study) for at least 6 months before study entry considered low-to-moderate
      risk using the 2013 American College of Cardiology (ACC)/American Heart Association (AHA)
      guideline thresholds for recommended statin initiation. Total study duration will be
      approximately 96 months from the time the first participant is enrolled.

      Participants will be randomly assigned to receive 4 mg of pitavastatin or placebo once a day
      for the entire time they are enrolled in the study. Study visits will occur at study entry
      (Day 0) and Months 1 and 4. Starting at Month 4, study visits will occur every 4 months for
      the rest of the study. Depending on when participants enroll, they will be in the study for a
      total of 3 to 8 years. Study visits will include medical and medication history reviews,
      physical examinations, blood collections, assessments and questionnaires, urine collections
      (for some participants), and an electrocardiogram (ECG) (at study entry only).

      Some participants will have the option of enrolling in a substudy (Effects of Pitavastatin on
      Coronary Artery Disease and Inflammatory Biomarkers: Mechanistic Substudy of REPRIEVE
      [A5333s]). The substudy will evaluate the effect of pitavastatin on the progression of
      non-calcified coronary atherosclerotic plaque (NCP) and inflammatory biomarkers in adults
      infected with HIV. Participants in the substudy will attend study visits at study entry and
      Months 4 and 24. The visits will include questionnaires and assessments, a blood collection,
      and a coronary computed tomography angiography (CCTA). NOTE: The Mechanistic Substudy of
      REPRIEVE (A5333s) closed to accrual on 02/06/18.

      Participants enrolled in REPRIEVE from select study sites, including international sites,
      through December, 2017, are included in the REPRIEVE Kidney Function Objectives Cohort to
      evaluate the effects of pitavastatin on parameters of kidney function in the setting of HIV
      infection. The analyses will also include an assessment of high risk groups and mechanisms
      driving kidney function decline in the setting of HIV infection.

      Women and men enrolled in REPRIEVE after February, 2016 are included in an observational
      cohort (REPRIEVE Women's Objectives Cohort) facilitating assessment of sex-specific
      mechanisms of CVD risk and risk reduction among adults with HIV. This effort also includes an
      evidence-based recruitment campaign to enhance women's participation in REPRIEVE.

      In response to the SARS-Cov-2 pandemic, a supplemental objective was added in 2020. To better
      understand how COVID-19 affects PWH and if pitavastatin may reduce risk, we will evaluate
      interrelated but independent key topics including epidemiology, host factors, and protective
      strategies. Starting from April 2020, COVID-19 assessment is completed at each study visit,
      and blood is collected for COVID-19 biomarkers.
    

Intervention name(s): Pitavastatin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): One tablet (4 mg) taken once daily, orally with or without food; One tablet taken once daily, orally with or without food
Intervention MeSH terms: Pitavastatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: HIV; Cardiovascular Disease; Myocardial Infarction; Inflammation; Statin; Computerized Tomography; Cholesterol; COVID-19