Protease Inhibitors and Cardiovascular Outcomes in Patients With HIV and Heart Failure

Abstract

BACKGROUND Incident heart failure (HF) is increased in persons with human immunodeficiency virus (PHIV). Protease inhibitors (PIs) are associated with adverse cardiac remodeling and vascular events; however, there are no data on the use of PIs in PHIV with HF. OBJECTIVES This study sought to compare characteristics, cardiac structure, and outcomes in PHIV with HF who were receiving PI-based versus non-PI (NPI) therapy. METHODS This was a retrospective single-center study of all 394 antiretroviral therapy–treated PHIV who were hospitalized with HF in 2011, stratified by PI and NPI. The primary outcome was cardiovascular (CV) mortality, and the secondary outcome was 30-day HF readmission rate. RESULTS Of the 394 PHIV with HF (47% female, mean age 60 ± 9.5 years, CD4 count 292 ± 206 cells/mm3),145 (37%) were prescribed a PI, whereas 249 (63%) were prescribed NPI regimens. All PI-based antiretroviral therapy contained boosted-dose ritonavir. PHIV who were receiving a PI had higher rates of hyperlipidemia, diabetes mellitus, and coronary artery disease (CAD); higher pulmonary artery systolic pressure (PASP); and lower left ventricular ejection fraction. In follow-up, PI 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. Predictors of CV mortality included PI use, CAD, PASP, and immunosuppression. Overall, PIs were associated with a 2-fold increased risk of CV mortality. CONCLUSIONS PI-based regimens in PHIV with HF are associated with dyslipidemia, diabetes, CAD, a lower left ventricular ejection fraction, and a higher PASP. In follow-up, PHIV with HF who are receiving a PI have increased CV mortality and 30-day HF readmission.

The potential role of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) single‐tablet regimen in the expanding spectrum of fixed‐dose combination therapy for HIV

“…Use of protease inhibitors has been associated with increased risk of myocardial infarction (MI), which was significantly increased with cumulative use of indinavir, lopinavir/r, and possibly DRV, although the latter remains controversial . Boosted protease inhibitors, specifically DRV, have also been associated with worsening outcomes in patients with heart failure . ABC and didanosine were also associated with a significantly increased risk of MI in some, but not all, cohort studies, and were not in RCTs .…”

Cardiovascular Considerations in Treating Patients With Coronavirus Disease 2019 (COVID-19)

“…29,30 A retrospective, single-center study suggests that ritonavir-boosted regimens may worsen cardiovascular outcomes in patients with HIV and heart failure. 31 Importantly, these data are not sufficient to restrict the use of lopinavir/ritonavir in patients with cardiovascular disease or heart failure given the life-threatening potential of COVID-19 and short-term (2 weeks) duration of treatment.…”

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“…This situation also applies to their behavior in the context of limited ability to follow the messages for preventive behavior: cognitive deficits or disorders of various degrees. Cardiovascular risks [96] and heart failure, possibly evoking from protease inhibitors (PI) [97], in people living with HIV pose particular challenges.…”