Patients with both HIV infection and heart failure whose antiretroviral regimen includes ritonavir-boosted protease inhibitors may be at greater risk for worsening of heart failure and cardiovascular death than patients with HIV taking nonprotease-inhibitor-based regimens. The study from Massachusetts General Hospital (MGH) investigators, which will appear in the August issue of the Journal of the American College of Cardiology, focused on patients who had been hospitalized for heart failure and were taking ritonavir-boosted protease inhibitors, which previous studies have associated with other vascular events.

“The use of protease inhibitors—specifically in combination with ritonavir—is an important treatment strategy for some persons with HIV,” says Tomas Neilan, MD, MPH, MGH Division of Cardiology, senior author of the JACC report. “While studies have demonstrated associations between some protease inhibitors and events such as heart attack and stroke, this is the first to note an effect of ritonavir-boosted protease inhibitor regimens on heart failure events.”

It has already been shown that persons with HIV have twice the risk of developing heart failure as do those without the infection; and as the number of persons with HIV who are over age 50 grows—largely because of the success of antiretroviral therapy—the rates of heart failure are projected to increase. In work previously published in JACC, Neilan’s group noted that individuals with both HIV and heart failure are at four times the risk of needing to be hospitalized for worsening heart failure symptoms and three times the risk of cardiovascular death. The current study was a step toward asking why heart failure outcomes were worse in HIV and was designed specifically to investigate the association between ritonavir-boosted protease inhibitor use and worse heart failure outcomes in persons with HIV.

The research team examined the records for 394 persons with HIV and heart failure who were receiving antiretroviral therapy and were admitted for worsening heart failure symptoms to the Bronx-Lebanon Hospital Center of Icahn School of Medicine at Mount Sinai in New York. During that hospital admission, the 145 patients whose antiretroviral therapy included ritonavir-boosted protease inhibitors were more likely than those not taking protease inhibitors to have elevated blood lipids, diabetes, coronary artery disease, elevated pulmonary artery pressure, and a reduced left ventricular emission fraction, a measure of the strength with which the heart beats.

In the 2 years after hospital admission, 35% of those taking ritonavir-boosted protease inhibitors died from cardiovascular causes, compared with 17% of those on nonprotease inhibitor antiretroviral regimens. Controlling for the severity of heart failure upon original hospitalization or for the specific type of protease inhibitors taken did not significantly change the association between ritonavir-boosted protease inhibitor treatment and cardiovascular death. Taking a protease inhibitor also doubled—from 34% to 68%—the risk that a patient would need to be readmitted to the hospital within 30 days of discharge.

Neilan and his colleagues note that, since this was a retrospective study conducted at a single institution among patients who had been hospitalized for heart failure—indicating they were already at elevated cardiovascular risk—larger studies, including patients receiving outpatient heart failure treatment, are required before the findings can be translated into clinical practice.

He says, “Persons with HIV and heart failure on any regimen warrant close monitoring with regular follow-up with their cardiologists and their HIV treatment providers, as well as tight control of cardiovascular risk factors such as hypertension, hyperlipidemia, and diabetes. We also need to better understand why persons with HIV have higher rates of heart failure and why their outcomes are worse. This study is a small step toward that better understanding.”