Public Release: 

Protease inhibitors may increase risk of death in people with HIV and heart failure

Ritonavir-boosted protease inhibitors associated with doubled risk of hospital readmission within 30 days, cardiovascular death within two years

Massachusetts General Hospital

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 non-protease-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 two years after hospital admission, 35 percent of those taking ritonavir-boosted protease inhibitors died from cardiovascular causes, compared with 17 percent of those on non-protease-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 percent - 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."


Neilan is an associate professor of Medicine at Harvard Medical School. The lead author of the JACC paper is Raza Alvi, MD, MGH Cardiology and Bronx-Lebanon Hospital Center. Additional co-authors are Anne Neilan, MD, MPH, and Virginia Triant, MD, MPH, MGH Division of Infectious Diseases; Adam Rokicki and Connor Mulligan, MGH Cardiology; Magid Awadalla, MD, and Dahlia Banerji, MD, MGH Radiology; Maryam Afshar, MD, Bronx-Lebanon Hospital Center; Noor Tariq, MD, Yale New Haven Hospital; and Markella Zanni, MD, Harvard Medical School.

Support for the study includes National Heart, Lung and Blood Institute grants 1R01 HL130539-01A1, 1R01 HL137562-01A1 and 5T32 HL076136; National Institutes of Health/Harvard Center for AIDS Research grant P30 AI060354; American Heart Association Fellow to Faculty Award 12FTF12060588 and a grant from the Kohlberg Foundation.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $900 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, genomic medicine, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, photomedicine and transplantation biology. The MGH topped the 2015 Nature Index list of health care organizations publishing in leading scientific journals and earned the prestigious 2015 Foster G. McGaw Prize for Excellence in Community Service. In August 2017 the MGH was once again named to the Honor Roll in the U.S. News & World Report list of "America's Best Hospitals."

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