Study FAQ

Previous studies have shown that HIV-infected individuals are at higher risk for heart disease than individuals without HIV. The REPRIEVE trial is testing a strategy to reduce the risk of heart disease –including heart attack and stroke – among people with HIV. In people with HIV, cardiovascular disease risk is thought to be influenced by traditional risk factors – such as cigarette smoking, high blood pressure, diabetes, and high cholesterol – and also by factors unique to HIV, such as chronic inflammation.

Will pitavastatin lower heart disease risk in both women and men with HIV?

Does pitavastatin help slow or prevent kidney disease in people with HIV?

How are people with HIV impacted by COVID-19?

What are the potential effects of a daily dose of pitavastatin and/or ART regimens on COVID-19?

Does a daily dose of pitavastatin lower the risk of heart-related disease among people with HIV?

Is COVID-19 a heart disease risk factor?

Statins are medications that lower cholesterol levels in the blood and have also been shown to have anti-inflammatory effects. Statins have already been shown to reduce the risk of heart disease in the general population among individuals at high risk for heart disease based on traditional risk factors. At the conclusion of REPRIEVE, we will know whether statins reduce the risk of heart disease among HIV-infected individuals with low to moderate traditional risk scores.

Participants were randomized (like flipping a coin) to take either:

• Pitavastatin calcium (Livalo) 4 mg, one pill daily
• Placebo for pitavastatin calcium (Livalo), one pill daily
Pitavastatin calcium (Livalo) is a statin that has been approved by the US Food and Drug Administration for the treatment of high cholesterol, even though not all participants in the trial have high levels of cholesterol, as per the trial design. Advice on healthy diet and exercise is given to all participants in the trial. Pitavastatin calcium (Livalo) has been shown to be safe in individuals taking antiretroviral (ART) medications.

REPRIEVE has enrolled over 7500 people with HIV into the trial.

Participants have visits approximately every 4 months during the trial. Trial participation for individual participants will be on average 6 years.

The REPRIEVE trial is being conducted at research sites in United States, Canada, Thailand, South Africa, Brazil, Peru, Haiti, Zimbabwe, Botswana, Uganda, and India. Over 100 research sites enrolled participants into REPRIEVE. A map is posted providing links to participating sites, as well as contact information for the site.

There are 6 substudies that are part of the REPRIEVE trial, including 2 additional study objectives included in REPRIEVE, they are:

• The REPRIEVE Mechanistic Substudy (ACTG A5333s)
• Pitavastatin to REduce Physical Function Impairment and FRailty in HIV (PREPARE) (ACTG #A5361s)
• Sex-Specific Mechanisms of Cardiovascular Disease Risk and Risk Reduction
• Evaluate the Effect of Pitavastatin on Kidney Function in HIV-infected Persons
• Clonal hematopoiesis of indeterminate potential, incident cardiovascular outcomes
• Mechanisms of Cardiac Dysfunction in HIV and the Effect of Statins: A Cardiac MRI Study

The Mechanistic Substudy of REPRIEVE (ACTG A5333s) is trying to understand ways in which statin therapy may achieve this goal. Some possible ways include:

1. lowering cholesterol levels
2. lowering the degree of inflammation
3. stabilizing fatty plaques in the blood vessels surrounding the heart, preventing these plaques from rupturing.

805 participants enrolled in the REPRIEVE substudy and the last visit was completed summer of 2020. Substudy participants had some additional tests and monitoring, including CT scan of the heart’s blood vessels.

Pitavastatin to REduce Physical Function Impairment and FRailty in HIV (PREPARE) [ACTG #A5361s]

PREPARE is an observational study of muscle strength and function among HIV-infected adults who are receiving pitavastatin or placebo as part of the REPRIEVE study (A5332) and are also enrolled in the Mechanistic substudy (A5333s). 600 REPRIEVE participants are also participating in the PREPARE substudy.

Sex-Specific Mechanisms of Cardiovascular Disease Risk and Risk Reduction

This objective is exploring among participants in REPRIEVE, differences in immune activation in relation to heart disease events. Another important part of this objective is to assure increased participation among women in REPRIEVE.

Evaluation of the Effects of Pitavastatin on Kidney Function in HIV-infected Persons

To evaluate the effects of pitavastatin on clinical and subclinical kidney function and to investigate the relationship between CKD and CVD.

Clonal Hematopoiesis of Indeterminate Potential, Incident Cardiovascular Outcomes

The objective is to estimate the prevalence of & characterize risk factors for CHIP in PWH, associate CHIP w/ incident clinical outcomes in PWH, and discover mechanistic relationships of CHIP w/ HIV-associated outcomes.

Mechanisms of Cardiac Dysfunction in HIV and the Effect of Statins: A Cardiac MRI Study

The objective is to characterize the epidemiology and pathobiology of COVID, especially regarding CVD and PWH, identify host factors influencing risk with respect to COVID and related CV outcomes, and determine whether statin therapy protects against COVID and/or mitigates severity.

REPRIEVE is funded by the National Heart Lung and Blood Institute (NHLBI) at the National Institutes of Health (NIH), with significant support and collaboration from the National Institute of Allergy and Infectious Diseases (NIAID) through its Division of AIDS (DAIDS). In addition, Kowa Pharmaceuticals America, Inc. is donating pitavastatin and providing support for the study. Gilead Sciences, Inc. and ViiV Healthcare are also providing support. The REPRIEVE trial is a collaboration of government agencies, academic centers, research institutes and industry support working in partnership to determine if pitavastatin can reduce the risk of cardiovascular disease in people with HIV infection who are taking HIV medications.

REPRIEVE is examining whether statin therapy protects against or decreases the severity of COVID-19 in the REPRIEVE global cohort. REPRIEVE trial leadership recently received a grant from the NIH National Heart Lung and Blood Institute to carry out this investigation.