February 13th, 2017

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

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:

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!

2 Responses to “How to Make Preventing Heart Disease in HIV Fun and Exciting: The REPRIEVE Trial”

  1. Schuyler Livingston says:

    I fear we will see a negative result with REPRIEVE because only fairly low risk patients will be referred (age 40-50, controlled HIV, without risk factors), and few events will occur.

  2. Michael Saag says:

    Nice piece, Paul. One interesting finding is the work by Heidi Crane is that among HIV individuals who experienced a documented (adjudicated) MIs, roughly half were Type 1 MI (classic atherosclerotic associated MI ) and half were Type II MIs (supply – demand mismatch), which occurred in younger HIV folks (http://jamanetwork.com/journals/jamacardiology/article-abstract/2594835).
    The question re use of statins should have most impact on Type I MIs…The REPRIEVE investigators will break down the Types of MIs as a primary outcome (almost certainly). It will be interesting to see what the REPRIEVE study reveals re protection of Type I vs Type II MIs.

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

Contributing Editor

NEJM Journal Watch
Infectious Diseases

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