REPRIEVE—A Large Trial for a Growing Problem among People with HIV

NIAID Now | May 29, 2019

A health worker selects a bottle of study drug at a South African clinic running the REPRIEVE trial, also known as A5332.

Credit: NIAID

Over the past decade, HIV clinicians report diagnosing fewer cases of life-threatening, opportunistic infections among patients taking medications that suppress the virus. The trend is a major testament to the progress made in responding to this once uniformly fatal disease. As a result, people with HIV are living longer than ever before. However, clinicians are seeing more instances of HIV-related cardiovascular disease, which has emerged as a leading cause of death among people with HIV. Studies have shown that a person with HIV is up to twice as likely as an HIV-negative person to experience a heart attack or stroke—even when the virus is well controlled with antiretroviral therapy, or ART.

Recognizing this disparity, researchers launched the Randomized Trial to Prevent Vascular Events in HIV, or REPRIEVE, in 2015 with support from NIAID and the National Heart, Lung and Blood Institute (NHLBI), both parts of NIH. The ambitious trial is testing the ability of a statin medication to reduce the risk of heart disease in men and women with HIV. Researchers completed the enrollment phase of the trial earlier this year, welcoming more than 7,500 participants in eleven countries. REPRIEVE investigators and NIAID collaborators discussed the design and goals of the trial in the June issue of the American Heart Journal. The article is now available online.

Researchers believe HIV increases a person’s risk for heart disease in part by persistently activating the immune system even when the virus is suppressed by ART. This chronic activation can lead to both a surplus of clotting compounds and inflamed blood vessels—both major risk factors for serious cardiovascular events like heart attack and stroke.  Statins work to lower heart disease risk by both lowering cholesterol levels and by targeting immune activation.  Since people with HIV experience persistent immune activation,  it is likely an even more important cause of heart disease than in people without HIV.

In the new publication, researchers write that REPRIEVE is the first major Phase 3 trial investigating a prevention strategy—a statin medication called pitavastatin—for heart disease in people with HIV. Pitavastatin is already approved by the U.S. Food and Drug Administration to prevent cardiovascular disease in older people; REPRIEVE will help determine whether early introduction of pitavastatin can further reduce cardiovascular events in people with HIV. This particular statin was chosen for the trial because it does not interact with HIV medications.

Importantly, investigators note that they will probe why women with HIV are even more likely to experience heart disease than male counterparts. This novel embedded study within REPRIEVE, called Follow YOUR Heart, will assess how sex differences influence the mechanisms, risk and treatment of heart disease in the context of HIV. Ultimately, physicians may be able to tailor the way they assess and treat the hearts of women living with HIV with evidence specific to both their patient’s sex and HIV status.

Learn more about the REPRIEVE trial.


S. Grinspoon et al. Rationale and Design of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE).  American Heart Journal DOI: 10.1016/j.ahj.2018.12.016 (2019).

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