Cardiovascular disease: the next great challenge for HIV care

On the first World AIDS Day in 1988, the outlook was bleak for people living with this strange, new, and deadly disease. Few could imagine the amazing progress to come in HIV treatment that has allowed millions of people around the world to live longer and healthier lives. The remarkable successes in treating HIV have led to a new challenge: Age-related chronic conditions have become a growing problem among people living with HIV in the United States and are poised to become a serious problem globally.

This World AIDS Day, as we focus on ending the transmission of HIV and finding a cure, it’s also important to help protect the millions of people ages 50 and older around the world living with HIV from age-related chronic conditions.

In this population, cardiovascular disease has emerged as a particularly troubling health problem. HIV-positive individuals are up to twice as likely to have heart attacks or strokes or develop other forms of cardiovascular disease than those not infected with the virus. That’s an alarming statistic, since cardiovascular disease is the leading cause of death for men and women in the United States. Despite its substantial impact, cardiovascular care is not always on the radar of HIV care providers.

Before the approval of the first effective anti-HIV drug, azidothymidine (AZT), in 1987, most people infected with HIV lived only a few years before dying of AIDS. Since then, the average age of Americans living with HIV has increased dramatically. Today, nearly half of people with HIV in the U.S. are age 50 or older. A similar shift has been happening around the world since 2007, a welcome trend that can be chalked up to effective HIV treatment and slowing transmission rates.

With these major advancements come parallel increases in non-AIDS conditions, like cardiovascular disease, diabetes, and kidney disease, over a lifetime of HIV infection. People living with HIV demonstrate increased inflammation and activation of the immune system — two precursors to heart disease — even when medications effectively suppress HIV in the body.

I have been studying the connection between HIV infection and cardiovascular disease for well over a decade. In one of the first research studies I oversaw, I vividly remember being struck by the amount of coronary plaque — cholesterol-filled inflammatory debris clogging the inside of arteries that nourish the heart — among young HIV patients who did not have any symptoms of heart disease. This plaque can become unstable and rupture, leading to sudden chest pain, heart attack, and stroke.

Over the past decade, rising rates of heart attack, stroke, and plaque buildup among individuals living with HIV caught the attention of the research community. Recent large epidemiological studies have confirmed what my colleagues and I were seeing in the clinic. Individuals with HIV have a 50 percent to 100 percent increase in the rate of cardiovascular events (heart attacks and strokes) compared to HIV-negative individuals and, on average, people living with HIV experience cardiovascular events at younger ages. Women and people of color are disproportionately affected by these complications.

Today, cardiovascular disease is among the leading causes of death among people with HIV. The HIV research community faces a critical need to better understand the mechanism of HIV-related cardiovascular disease and other age-related complications and urgently develop effective treatment strategies for them.

To that end, the ongoing Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) trial, for which I am a principal investigator, offers a major step in addressing the unacceptable burden of heart disease among those living with HIV. The trial, supported by the National Institutes of Health, provides an important opportunity to develop a cardiovascular disease prevention strategy uniquely tailored for this vulnerable population.

REPRIEVE will test whether taking a statin medication can prevent cardiovascular events like heart attacks and strokes in people with HIV by simultaneously lowering cholesterol and reducing inflammation. The trial will enroll 6,500 participants across approximately 130 sites in the U.S., Canada, Brazil, South Africa, Thailand, Botswana, Peru, Haiti, Uganda, Zimbabwe, and India. With sites all over the world, REPRIEVE — the largest study to date on HIV and cardiovascular disease — will reflect the diversity of the global population affected by HIV.

This ambitious trial aims to fill a huge gap in the care of older people living with HIV. This community needs strategies to prevent heart attacks, strokes, and other complications that we are likely to see with increasing frequency as people with HIV age. The results of REPRIEVE could improve the health of this population for years to come.

These age-related complications of HIV could not have been recognized without past victories in HIV and AIDS research that led to longer lives. But we can’t stop there — we now have an obligation to deliver new research victories to ensure that these longer lives are as healthy as they can possibly be.

Steven K. Grinspoon, M.D., is director of the Program in Nutritional Metabolism at Massachusetts General Hospital; professor of medicine and director of the Nutrition Obesity Research Center at Harvard Medical School; and co-principal investigator of the REPRIEVE Clinical Coordinating Center.