How to Make Preventing Heart Disease in HIV Fun and Exciting: The REPRIEVE Trial

February 13, 2017

Paul E. Sax, M.D.

Paul E. Sax, M.D., is director of the HIV Program and Division of Infectious Diseases at Brigham and Women's Hospital in Boston.

The people researching cardiovascular disease in HIV have quite the challenge.

Because when you think about it for a second, we HIV treaters are a pretty spoiled bunch when it comes to therapeutic success.

We saw the transformation of a terrifying, incurable, and rapidly progressive disease (AIDS) into something that can be managed for decades -- usually with just a pill or two each day.

Or, if you prefer a quantitative description, here's the slide Tony Fauci uses when he cites my friend Rochelle Walensky's 2006 landmark paper in his talks:

AIDS drugs have saved 3 million years of life in the United States

Remember, these impressive numbers were estimated before we had the great advances in antiretroviral therapy in the late 2000s. The benefits are undoubtedly even greater over the last decade, since virtually everyone who takes HIV medications regularly now is virologically suppressed.

Pretty much any medical intervention for a non-HIV problem might seem a bit ho-hum compared to the miracle of antiretroviral therapy, meaning the people researching non-HIV related problems have their work cut out for them to get our attention. This is despite the fact that these non-HIV problems (especially the problems of aging) are more important than ever.

So when Steve Grinspoon contacted me recently about mentioning the REPRIEVE study on this site in honor of "Heart Month", I readily agreed. Steve is leading this large NIH-funded trial, which asks this important question:

If people with HIV are intrinsically greater risk of heart disease, would they benefit from taking a statin drug even if we would not ordinarily prescribe it based on standard risk assessments?

REPRIEVE is actively enrolling at clinics and hospitals around the world, including at our site here in Boston.

As demonstrated in multiple studies (and reviewed here), people with HIV do appear to be at higher risk for heart disease even when their virus is well controlled with ART. "Lifestyle" issues (especially smoking), current and past immunosuppression, duration of uncontrolled viral replication, cardiotoxic drugs, and immune activation and inflammation all likely play a role. Related to the issue of inflammation, Steve's research group just published a paper demonstrating that abnormal arterial inflammation -- a risk factor for coronary disease -- continues despite effective ART, at least in the short term.

So why not just recommend a statin for all people with HIV above a certain age? While it's theoretically possible that statins will improve this abnormal inflammatory state, we don't know that statins will provide a clinical benefit. And perhaps not all people with HIV are at higher CV risk -- the most recent look at MI incidence in the Kaiser HIV cohort did not find an excess risk in a group of very healthy (high CD4, modern ART regimens, low rates of smoking) HIV patients compared to HIV negative controls.

Which brings us back to REPRIEVE -- statins might be beneficial, they might not, and there's enough equipoise that it's appropriate to conduct a real randomized trial.

Eligible patients must have stable HIV, be older than 40, and not have a high risk for heart attacks or stroke (otherwise they should be on a statin). If you want to check, you can enter patient information into the American College of Cardiology/American Heart Association heart risk calculator. Those with a 10-year risk of heart disease or stroke < 15% may be eligible, depending on LDL cholesterol levels.

Participants are then randomized to pitavastatin (chosen because it doesn't interact with any HIV drugs) or placebo. The primary endpoint is time to atherosclerosis-related clinical event.

I think it's an excellent study, not just because I've known Steve for ages and he's been a leading figure researching metabolic complications of HIV disease longer than just about anyone. A clinical trial that evaluates a critical non-HIV related complication makes abundant sense in a population where infectious complications are increasingly rare. The results will have great importance to patients, in particular the increasing proportion over the age of 50 (which now exceeds 50% in many urban areas).

Plus, if I mention REPRIEVE here, maybe I'll get him to read this blog -- which he obviously had never done before he called me. "I've been really busy," he said.

Too busy to read Fun With Old Medical Images? To weigh in on whether ID doctors are the worst dressed specialists? To talk about doctors named Morgan? Or if we should wear white coats?

"Really busy"? -- not sure I'm buying that excuse!

Get email notifications every time HIV Care Today is updated.

This article was provided by NEJM Journal Watch. NEJM Journal Watch is a publication of the Massachusetts Medical Society.
See Also
Rosuvastatin Slows Subclinical Atherosclerosis in HIV Group With Normal LDL-Cholesterol
This Week in HIV Research: Reducing Cardiovascular Risk; and Monitoring Renal Function With PrEP
This Week in HIV Research: HIV-Related Inflammation May Be Irreversible; and Genetically Engineered T-Cells Resist HIV

No comments have been made.

Add Your Comment:
(Please note: Your name and comment will be public, and may even show up in
Internet search results. Be careful when providing personal information! Before
adding your comment, please read's Comment Policy.)

Your Name:

Your Location:

(ex: San Francisco, CA)

Your Comment:

Characters remaining:


The content on this page is free of advertiser influence and was produced by our editorial team. See our content and advertising policies.