Scientists have long known that people living with HIV have an increased risk of heart disease.statin However, the drug pitavastatin may offer a solution.
In a Phase 3 clinical trial, people with HIV who took pitavastatin, a drug that lowers cholesterol, were 35% less likely to have a serious heart complication such as heart attack, heart failure or stroke. The findings were published Sunday in the New England Journal of Medicine and were presented at a meeting of the International AIDS Society in Brisbane, Australia.
This report provides promising new ways for people living with HIV to better manage their heart health.
HIV (Human Immunodeficiency Virus) attacks and weakens the body’s immune system, leaving patients vulnerable to other (often fatal) diseases. There is no cure, but treatment with antiretroviral drugs can help control the disease and lead a more normal life.
But Dr. Patrice Desvigne-Nickens, a physician at the Department of Cardiovascular Sciences at the National Heart, Lung and Blood Institute, who was involved in the trial, said people with HIV have up to twice the risk of heart disease and cardiovascular complications compared to the general population. Cardiac complications occur much earlier and are more fatal for HIV-infected people.
Scientists don’t know the exact reason, but experts believe it may be the result of HIV’s high and persistent inflammation and chronic immune activation.
“This is becoming a big problem for the HIV community,” said Stephen Grinspoon, Ph.D., professor of medicine at Harvard Medical School and lead author of the study. “Despite receiving effective antiretroviral therapy, they still have heart attacks and strokes. They don’t have HIV-specific comorbidities. They have heart disease.”
The study, named the REPRIEVE trial, recruited more than 7,700 participants worldwide, aged 40 to 75, all of whom were HIV-infected, currently taking antiretroviral medications, and assessed as having low to moderate risk of heart disease.
Each participant was randomly assigned to take pitavastatin or a placebo tablet daily. In this double-blind setting, neither the patient nor the attending physician knew which treatment they were receiving.
Pitavastatin belongs to a class of medicines called statin It reduces the amount of cholesterol made by the liver and helps the liver break down cholesterol in the blood. As a result, the drug lowers low-density lipoprotein (LDL) cholesterol (“bad cholesterol,” as Desvigne Nickens puts it) that builds up in blood vessels and can cause heart problems.
It was specifically selected for HIV trials because it does not interact with antiretroviral drugs and is “amazingly perfect,” Desvigne-Nickens said. The drug is also widely available at a “relatively cheap” price, Grinspoon noted.
However, pitavastatin is not usually given to patients at “low to moderate” risk of heart disease, such as those with HIV. The American Heart Association and American College of Cardiology standard risk assessments include criteria such as age, sex, and ethnicity, but do not include HIV-related cardiovascular risk factors.
This omission creates a blind spot for HIV patients who have low risk assessment scores and are not prescribed pitavastatin, yet still have a disproportionately high incidence of heart disease.
“In the absence of data, the risk is in the low to moderate range and primary preventive drug strategies are generally not recommended,” Grinspoon said. “Here he REPRIEVE fits very well.”
In the trial, researchers found that HIV-positive patients taking pitavastatin were about 35% less likely to experience “adverse” cardiovascular events such as heart attacks than controls. A 21 percent reduction in cardiovascular events and deaths in patients was also observed, Desvigne-Nickens said.
But if pitavastatin simply lowered LDL cholesterol levels, the cardiovascular risk reduction would be only 17%, Grinspoon calculated. This is less than half the risk reduction in the trial.
As a result, the report suggests that statin therapy does more than just lower LDL levels. It also reduces immune activation and inflammation that puts her HIV-positive at risk for heart disease in the first place.
And the researchers found similar treatment effects among various subgroups, including women and the international population. Overall, researchers found a consistent reduction in cardiovascular risk.
For Desvigne-Nickens, it was a “slam dunk.”
“This is incredibly positive,” Desvigne Nickens said. “It was incredible that this drug exceeded our expectations.”
In fact, the study was stopped early after about five years per participant. After reviewing data from the middle three-quarters of the REPRIEVE trial, an independent safety panel had enough data to know the drug was “very effective,” she explained. This exceeded expectations.
“This 35% reduction was so compelling that we were able to stop the trial,” said Desvigne Nickens. “They knew the answer. They knew this drug would be very effective in reducing these adverse cardiac events.”
“Usually this is only done when results are very strong,” Grinspoon added.
Participants taking pitavastatin also developed diabetes, a known side effect of statins, at a slightly higher rate: 5% versus 4% in controls. Grinspoon noted that pitavastatin is similarly effective in reducing cardiovascular risk in people with diabetes.
He doubts many physicians will start incorporating the findings into clinical practice. And he hopes the results of the study will encourage regulators to consider incorporating pitavastatin into the standard of care for people living with HIV.
“It’s very generalizable and rigorous in terms of its randomized, placebo-controlled, double-blind design,” he says. “And based on the large group of people targeted, I think it could be considered of sufficient importance to be incorporated into the guidelines. I think the community would agree that these guidelines would be incorporated.”
The researchers’ optimism stems from the varied scope of the trials. The study was conducted in 12 countries, including several countries in sub-Saharan Africa, Asia, South America, and the Caribbean, where HIV prevalence is high.
Thirty percent of the study participants were female and 65% were non-Caucasian, Grinspoon explained, a striking comparison to studies that have historically ignored these populations.
“We thought it was important to make the trial more global and diverse,” he added. “This is truly a global trial. Now I can say that this is a big test for all other groups as well.”
The researchers also hope that pitavastatin won’t become an undue burden on people taking antiretroviral drugs. As an available and affordable daily drug, it could be an easy addition to the medication routines of HIV-positive people who may already be on “complex medications,” Desvigne-Nickens said.
“We show that adding one tablet daily to antiretroviral therapy can prevent heart disease,” Grinspoon said. “Now we have evidence that something works for people to whom nothing is normally recommended.”