Evaluating the Use of Pitavastatin to Reduce the Risk of Cardiovascular Disease in HIV-Infected Adults

There are few strategies to prevent CVD in people with HIV (PWH), 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 PWH. The purpose of this study was to evaluate the use of pitavastatin to reduce the risk of CVD in PWH on ART. This study enrolled PWH who were on any ART regimen (ART was not provided by the study) for at least 6 months before study entry and were at low to moderate risk of CVD using the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guideline thresholds for recommended statin initiation. Participants were randomly assigned to receive 4 mg of pitavastatin or placebo once a day for their entire study duration. Pitavastatin or placebo could be discontinued and clinically indicated statin therapy initiated at the discretion of the site investigator or the participant's care provider, with the intention of following the participant according to the intention-to-treat trial design. Study visits occurred at study entry and Months 1 and 4. Starting at Month 4, study visits occurred every 4 months for the rest of the study. Depending on when participants enrolled, they were in the study for a total of 4 to 8 years. Study visits included 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). Participants at US sites had the option of enrolling in a substudy (Effects of Pitavastatin on Coronary Artery Disease and Inflammatory Biomarkers: Mechanistic Substudy of REPRIEVE \[A5333s\]). The substudy evaluated the effect of pitavastatin on the progression of non-calcified coronary atherosclerotic plaque (NCP) and inflammatory biomarkers in PWH. Participants in the substudy attended study visits at study entry and Months 4 and 24. The visits included questionnaires and assessments, a blood collection, and a coronary computed tomography angiography (CCTA). The Mechanistic Substudy closed to accrual on February 6, 2018, when its accrual target of 800 participants had been reached. Sites that enrolled participants into the Mechanistic Substudy are indicated with asterisk (\*) at the end of the institution names in the Contacts and Locations section. Participants enrolled in REPRIEVE from select study sites, including international sites, through December, 2017, were included in the REPRIEVE Kidney Function Objectives Cohort to evaluate the effects of pitavastatin on parameters of kidney function in the setting of HIV. These objectives include evaluating high risk groups and mechanisms driving kidney function decline in the setting of HIV. Women and men enrolled in REPRIEVE after February, 2016 were included in an observational cohort (REPRIEVE Women's Objectives Cohort) facilitating assessment of sex-specific mechanisms of CVD risk and risk reduction among PWH. This effort also included 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 the risk of serious COVID-19 disease, we evaluated interrelated but independent key topics including epidemiology, host factors, and protective strategies. Starting from April 2020, COVID-19 assessment was completed at each study visit, and blood was collected for COVID-19 biomarkers. The data and safety monitoring board (DSMB) recommended stopping the trial for efficacy at the second planned review on March 30, 2023, and concluded that no unexpected safety concerns had been reported. Following the DSMB action, participants were asked to return for the final study visit. All final visits were completed by August 21, 2023. We here present the results based on the final trial database, including the full follow-up out to closeout visits.