July 27, 2018
2 min read

Protease inhibitor therapy increases risk for CV events in HIV, HF

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Tomas G. Neilan

Patients with HF and HIV who were treated with protease inhibitors had an increased risk for CAD, dyslipidemia, diabetes, lower left ventricular ejection fraction and higher pulmonary artery systolic pressure, according to a study published in the Journal of the American College of Cardiology.

“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,” Tomas G. Neilan, MD, MPH, associate professor of medicine at Massachusetts General Hospital, said in a press release. “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.”

HF hospitalization

Raza Alvi, MD, research fellow in radiology at Massachusetts General Hospital, and colleagues analyzed data from 394 patients with HIV who were hospitalized for an acute primary diagnosis of acute decompensated HF in 2011. Patients were either treated with protease inhibitor (n = 145; mean age, 59 years; 45% women) or non-protease inhibitor therapy (n = 249; mean age, 60 years; 48% women). Those who recently underwent cardiac surgery, without HIV, and patients who were not prescribed antiretroviral therapy were excluded from the study.

Patient were then categorized by HF type: HF with reduced ejection fraction, HF with borderline ejection fraction and HF with preserved ejection fraction.

Covariates that were assessed included traditional HF risk factors, LVEF, medication use at hospital discharge and socioeconomic status.

The primary outcome was CV mortality, which was defined as death from arrhythmias, HF, sudden cardiac death and/or acute ischemic events. The secondary outcome was 30-day HF hospitalization readmission rate.

A boosted dose of ritonavir was used in all protease inhibitor regimens.

Compared with patients not treated with a protease inhibitor, those who received the treatment had increased rates of diabetes (44% vs. 31%; P = .012), hyperlipidemia (52% vs. 35%; P < .001) and CAD (52% vs. 33%; P < .001). These patients also had higher pulmonary artery pressure (48 mm Hg vs. 9 mm Hg; P < .001) and lower LVEF (44% vs. 49%; P = .003).

Increased CV events

During follow-up, patients treated with protease inhibitors had increased rates for readmission (68% vs. 34%; P < .001) and CV mortality (35% vs. 17%; P < .001) vs. those who were not treated with protease inhibitors. These effects were seen throughout all types of HF.

Factors associated with CV mortality included CAD, protease inhibitor use, immunosuppression and pulmonary artery systolic pressure. Protease inhibitor therapy increased the risk for CV mortality by twofold.

“Further research is needed to determine whether [protease inhibitor]-based regimens, either individual regimens or as a class effect, contribute pathophysiologically to processes leading to worse outcomes in HF (eg, myocardial fat and fibrosis) and whether these findings can be replicated in prospective cohorts,” Alvi and colleagues wrote.

“Data on medication adherence and viral suppression should be carefully collected because not only is medication adherence an important predictor of health outcomes among [persons with] HIV, but also differences by drug class may serve as important confounders for cardiovascular endpoints,” Robert S. Rosenson, MD, director of cardiometabolic disorders at Icahn School of Medicine at Mount Sinai, and Rupert Kaul, MD, PhD, professor at University of Toronto, wrote in a related editorial. – by Darlene Dobkowski

Disclosures: Alvi reports he received support from NIH/NHLBI. Neilan reports he received support from the Kohlberg Foundation, an American Heart Association Fellow to Faculty Award, NIH/NHLBI and NIH/Harvard Center for AIDS Research and served on the advisory board for Takeda. Rosenson and Kaul report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.