Heart disease, also known as cardiovascular disease (CVD), is higher by 50%–100% among people living with HIV. The reasons for this include traditional factors that elevate risk such as cigarette smoking, abnormal cholesterol levels, diabetes mellitus, and high blood pressure. But there may be other factors in people living with HIV, such as inflammation, that also play a significant role. The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) was conducted to address gaps in the prevention of CVD among people living with HIV and investigate a primary prevention strategy that could be safely and widely employed. Specifically, the trial aimed to employ a strategy that would be effective to prevent disease among the large group of people living with HIV who have low-to-moderate predicted CVD risk, who were nonetheless experiencing CVD at an increased rate. REPRIEVE utilized pitavastatin, a cholesterol lowering medicine that does not interfere with HIV treatment. REPRIEVE enrolled 7769 people with HIV in 12 countries across diverse regions through partnerships with many sponsors/investigators including the National Heart Lung and Blood Institute, the National Institute of Allergy and Infectious Diseases, and ACTG.
REPRIEVE demonstrated a 36% reduction in the primary endpoint of major adverse cardiovascular events (MACE) over 5.6 years. MACE was defined as myocardial infarction (heart attack), stroke, cardiovascular death, coronary revascularization (bypass surgery and stents), significant peripheral artery disease, hospitalization for unstable angina, or death from an undetermined cause. These results led to changes in guidelines issued by DHHS, AHA/ACC, HIVMA, European AIDS Society, British HIV Association, and IAS-USA among others who now recommend the use of statins in people with a 5% or higher estimated risk of developing cardiovascular disease.
A number of important findings have been generated from REPRIEVE, including:
- A study led by Kathleen Fitch helps us understand why some people develop diabetes mellitus when taking a statin. Metabolic risk factors including obesity, disorders of body metabolism and pre-diabetes are significant contributors to the development of diabetes irrespective of statin use. People who did not have these risk factors had a low chance of developing diabetes, even when taking a statin. These findings highlight the importance of addressing metabolic risk factors among people living with HIV to prevent diabetes (Fitch, Annals of Internal Medicine, 2024).
- Michael Lu led the mechanistic study that measured statin effects on noncalcified plaque (material that builds up in blood vessels to block them) over two years. This sub-study enrolled over 800 participants and demonstrated a significant reduction of higher-risk noncalcified plaque volume and reduction in plaque progression. Among those with plaque at study entry, noncalcified plaque volume was reduced by 12% (Lu, JAMA Cardiology, 2024).
- Steven Grinspoon and Markella Zanni reported that the most common risk assessment for heart disease, the Pooled Cohort Equation, underestimated the risk of developing MACE, particularly in women and those who identify as Black in high-income countries. The performance of the risk score in high-income countries improved when the score was multiplied by a factor of 2.8 for Black women, 2.6 for women who are not Black, and 1.25 for Black men (Grinspoon, Zanni, Lancet HIV, 2025).
- Carl Fichtenbaum presented data confirming a higher risk of MACE in people previously exposed to or currently taking abacavir leading to updated guidelines using this medication to treat HIV (Fichtenbaum, IAS 2024).
- Martin Kolossvary published data that is helping us unravel how statin therapy affects plaque in the heart’s blood vessels. A factor (gene) known as PCOLCE was increased in people taking pitavastatin in the REPRIEVE mechanistic sub-study. Increases in PCOLCE were associated with a decrease in noncalcified plaque, leading to the stabilization of plaques (Kolossvary, JAMA Cardiology, 2024).
“REPRIEVE has helped us learn a lot about heart disease in people with HIV. We are indebted to the study participants, investigators and staff that made this study possible. We look forward to learning much more about heart disease and how to mitigate its consequences in the coming years.” said Principal Investigator Steven Grinspoon.
For a list of all 47 REPRIEVE publications and lay summaries to date, visit www.reprievetrial.org/learnmore/reprieve-publications/.