This is a randomized trial to prevent vascular events in HIV, tests whether a daily dose of a statin will reduce the risk of cardiovascular disease among HIV-infected individuals (for whom statins are not already recommended according to 2013 US Cholesterol Treatment Guidelines).
Brief Summary: REPRIEVE (A5332) is a large double-blind, randomized, placebo-controlled study of pitavastatin or placebo for about 84 months (N = 590 (Thailand: RIHES 178 + HIV-NAT 412); n total = 7557). The trial is testing the effect of statin therapy on preventing heart disease and death in HIV-infected persons on HIV medications who do not meet guidelines for starting statins.
Known as the Randomized Trial to Prevent Vascular Events in HIV, or REPRIEVE, the multicenter international clinical trial is the largest trial to date focused on HIV-related cardiovascular disease. REPRIEVE will test whether statin administration can reduce the risk for major adverse cardiovascular events, such as heart attacks, strokes, and heart disease, in people with HIV infection. Researchers hypothesize that statins should reduce plaque development and improve cardiovascular outcomes in people with HIV. The ultimate objective of the trial is to inform the best clinical approach to preventing cardiovascular disease in people infected with HIV. The trial is supported by the National Institutes of Health’s National Heart, Lung, and Blood Institute (NHLBI) and National Institute of Allergy and Infectious Diseases (NIAID).
This study is currently not recruiting any more participants. We are following and monitoring 412 participants at our site.
Rationale: HIV-infected persons face an increased risk of CVD morbidity and mortality, yet no preventive strategies for CVD risk reduction have been proven for this population. Among HIV-infected individuals, immune activation may contribute in unique ways to atherosclerosis and ensuing cardiovascular events. Statins affect both traditional CVD risk factors (LDL cholesterol) and have pleiotropic effects to reduce inflammation and immune activation. Thus, statins may target the unique mechanisms of cardiovascular disease in HIV.
Why are we doing this study/ what is the benefit?
As Statins affect both traditional CVD risk factors (LDL cholesterol) and have pleiotropic effects to reduce inflammation and immune activation so we want to provide statin (study drug) to participants who are living with HIV for prevention of CVD risk but we also keep monitoring for the safety after taking the study drug. However, it is also possible that participants may receive no benefit from being in this study either because the drug may not work or because the participants are assigned to placebo
There were four presentations at CROI 2021 from the REPRIEVE Trial:
ASSESSMENT OF OBESITY AND METABOLIC PROFILE BY INTEGRASE INHIBITOR USE IN REPRIEVE
The investigators found that INSTI-based regimens were associated with:
- Higher BMI
- Higher waist circumference
- Higher odds of obesity
The investigators found that INSTI-based regimens were not associated with:
- Higher fasting blood sugar
- Higher fasting LDL cholesterol
- Higher odds of metabolic syndrome (includes metabolic changes of increased blood sugar, abdominal size, blood pressure, cholesterol levels)
- Higher odds of high blood pressure
These findings provide some reassurance that higher weight associated with INSTIs is generally not associated with increased cardiovascular risk for most participants. More studies that follow participants on INSTIs over time are needed to confirm these results.
DIET QUALITY BY GLOBAL BURDEN OF DISEASE REGION IN PEOPLE WITH HIV IN THE REPRIEVE TRIAL
The key findings were:
- Overall REAP score was optimal in only 13% of participants.
- The REAP Score was suboptimal or poor in 38% and 4% of participants, respectively.
- Participants residing in South Asia had the highest overall REAP score (better diet quality) and 61% of participants’ diet in this region was classified as optimal.
The investigators found that higher REAP score was associated with:
- Older age
- Less frequent alcohol use
- South East/East Asia and South Asia region of residence
The investigators found that lower REAP score was associated with:
- Sub-Saharan Africa region of residence
- Black or African American race (in High Income and sub-Saharan Africa regions)
In summary, among participants in REPRIEVE, there were substantial variations in diet quality reported by geographic region. Diet was suboptimal or poor for 42% of participants. Poor diet is an important risk factor for heart disease, which can be improved among a large proportion of people with HIV.
FACTORS ASSOCIATED WITH SYSTEMIC IMMUNE ACTIVATION IN A GLOBAL HIV COHORT
Results showed that female sex, living in a high-income region or in South Asia, and having a lower body mass index (a measure comparing weight to height) related to higher levels of soluble CD14, while male sex, living in a high-income region and having higher body mass index related to higher levels of oxidized LDL.
Future investigations may help us understand:
- Ways that medications such as statins (which lower cholesterol in the blood) and changes in behavior (for example, healthy diet) influence levels of inflammation markers.
- Whether lowering levels of these key inflammation markers helps protect against heart disease among people with HIV, possibly with different effects in females and males.
CORONARY ARTERY DISEASE, TRADITIONAL RISK AND INFLAMMATION AMONG PWH IN REPRIEVE
Results showed that 49% of participants had some coronary artery plaque and 35% had some coronary artery calcium. Overall, the degree of plaque was not severe. The extent of plaque increased, as expected, with atherosclerotic cardiovascular (ASCVD) risk score, a calculation of one’s risk of having a heart problem like heart attack or stroke. Markers of inflammation were associated with plaque even after adjusting for ASCVD risk score. Despite the fact that coronary plaque was relatively common, most often it did not block a significant proportion of the coronary artery.
These findings may help pave the way for the development of strategies to reduce or prevent further build-up of coronary artery plaque and thus improve heart health among people with HIV.
