Protease Inhibitors and Cardiovascular Outcomes in HIV and HF

Study Questions:

What are the characteristics, cardiac structure, and outcomes in persons with human immunodeficiency virus (HIV) with heart failure (HF) who were receiving protease inhibitor-based versus nonprotease inhibitor therapy?


The study authors conducted a retrospective single-center study of all 394 antiretroviral therapy–treated persons with HIV who were hospitalized with HF in 2011, stratified by protease inhibitor and nonprotease inhibitor therapy. The cohort was stratified by HF with reduced ejection fraction (HFrEF) (left ventricular ejection fraction [LVEF] <40%), HF with borderline ejection fraction (HFbEF) (LVEF 40-49%), and HF with preserved ejection fraction (HFpEF) (LVEF ≥50%). The primary outcome was cardiovascular (CV) mortality (defined as death resulting from HF, sudden cardiac death, arrhythmias, and/or acute ischemic events), and the secondary outcome was 30-day HF readmission rate.


Of the 394 persons with HIV with HF (47% female, mean age 60 ± 9.5 years, CD4 count 292 ± 206 cells/mm3), 145 (37%) were prescribed a protease inhibitor, whereas 249 (63%) were prescribed nonprotease inhibitor regimens. All protease inhibitor-based antiretroviral therapy contained boosted-dose ritonavir. Persons with HIV who were receiving a protease inhibitor had higher rates of dyslipidemia, diabetes mellitus, and coronary artery disease (CAD); higher pulmonary artery systolic pressure (PASP); and lower LVEF. In follow-up, protease inhibitor use was associated with increased CV mortality (35% vs. 17%; p < 0.001) and 30-day HF readmission (68% vs. 34%; p < 0.001), effects seen in all HF types.

Among the persons with HIV hospitalized with HFrEF, the CV mortality rate was higher among the individuals who were taking a protease inhibitor versus a nonprotease inhibitor (36% vs. 21%; p = 0.021). Among the persons with HIV hospitalized with HFpEF, the CV mortality rate was higher in the individuals taking a protease inhibitor versus a nonprotease inhibitor (33% vs. 15%; p = 0.004); and among the persons with HIV hospitalized with HFbEF, the CV mortality rate was also higher in the individuals who were taking a protease inhibitor versus a nonprotease inhibitor (35% vs. 4%; p = 0.01). Increased 30-day HF readmission rate with protease inhibitors were noted when groups were analyzed according to the type of HF: HFrEF with a protease inhibitor versus HFrEF not with a protease inhibitor (70% vs. 55%; p < 0.001); HFpEF with a protease inhibitor versus HFpEF with a nonprotease inhibitor (66% vs. 22%; p < 0.001); and HFbEF with a protease inhibitor versus HFbEF with an nonprotease inhibitor (65% vs. 23%; p = 0.01). Predictors of CV mortality included protease inhibitor use, CAD, PASP, and immunosuppression. Overall, protease inhibitors were associated with a twofold increased risk of CV mortality.


The authors concluded that protease inhibitor-based regimens in persons with HIV with HF are associated with dyslipidemia, diabetes, CAD, a lower LVEF, and a higher PASP. In follow-up, persons with HIV with HF who are receiving a protease inhibitor have increased CV mortality and 30-day HF readmission.


HIV, itself, is associated with 50-100% increased CV risk even after controlling for traditional risk factors (Eur Heart J 2014;35:1373-81). Although this was a single-center retrospective study, the finding that therapy for such patients may accelerate atherosclerosis and increase mortality is of concern. It is estimated that 1.1 million people in the US are infected, and more than 37,000 new cases are diagnosed every year. With the increasing burden of CV disease in HIV patients, it is time to examine a recent call to develop the subspecialty of ‘Cardio-Virology’ to serve this population (Am J Med 2018;131:726-7).

Clinical Topics: Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Atherosclerotic Disease (CAD/PAD), Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Pulmonary Hypertension

Keywords: Anti-Retroviral Agents, Arrhythmias, Cardiac, Atherosclerosis, Blood Pressure, CD4 Lymphocyte Count, Coronary Artery Disease, Death, Sudden, Cardiac, Diabetes Mellitus, Dyslipidemias, Heart Failure, HIV Infections, Hypertension, Pulmonary, Primary Prevention, Protease Inhibitors, Risk Factors, Ritonavir, Stroke Volume

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