Darunavir/cobicistat is associated with negative outcomes in HIV-negative patients with severe COVID-19 pneumonia.

Abstract

Background The aim of this study was to evaluate both positive outcomes, including reduction of respiratory support aid and duration of hospital stay, and negative ones, including mortality and a composite of invasive mechanical ventilation or death, in patients with COVID-19 pneumonia treated with or without oral darunavir/cobicistat (DRV/c, 800/150 mg/day) used in different treatment duration. Secondary objective was to evaluate the percentage of patients treated with DRV/c who were exposed to potentially severe drug-drug interactions (DDI) and died during hospitalization. Methods This observational retrospective study was conducted in consecutive patients with COVID-19 pneumonia admitted to a tertiary care hospital in Modena, Italy. Kaplan-Meier survival curves and Cox proportional hazards regression were used to compare patients receiving standard of care with or without DRV/c. Adjustment for key confounders was applied. Results 273 patients (115 on DRV/c) were included, 75.8% males, mean age was 64.6 (±13.2) years. Clinical improvement was similar between the groups, depicted by respiratory aid switch (p>0.05). The same was observed for duration of hospital stay [13.2 (±8.9) for DRV/c vs. 13.4 (±7.2) days, p=0.9]. Patients on DRV/c had higher rates of mortality (25.2% vs. 10.1%, p<0.0001), more pronounced in patients undergoing DRV/c for less than 5 days. The rate of composite outcome of mechanical ventilation and death was higher in the DRV/c group (37.4% vs. 25.3%, p=0.03). Multiple serious DDI associated with DRV/c were observed in the 19 patients who died. Conclusion DRV/c should not be recommended as a treatment option for COVID-19 pneumonia outside clinical trials.