Darunavir/Cobicistat Is Associated with Negative Outcomes in HIV-Negative Patients with Severe COVID-19 Pneumonia

Abstract

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 coronavirus disease 2019 (COVID-19) pneumonia treated with or without oral darunavir/cobicistat (DRV/c, 800/150 mg/day) used in different treatment durations. The secondary objective was to evaluate the percentage of patients treated with DRV/c who were exposed to potentially severe drug-drug interactions (DDIs) and died during hospitalization. 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. Two hundred seventy-three 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 > .05). The same was observed for duration of hospital stay [13.2 (-8.9) for DRV/c vs. 13.4 (-7.2) days for no-DRV/c, p = .9]. Patients on DRV/c had higher rates of mortality (25.2% vs. 10.1%, p < .0001. The rate of composite outcome of mechanical ventilation and death was higher in the DRV/c group (37.4% vs. 25.3%, p = .03). Multiple serious DDI associated with DRV/c were observed in the 19 patients who died. DRV/c should not be recommended as a treatment option for COVID-19 pneumonia outside clinical trials.

Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study

“…Use of DRV/c in COVID-19 patients has been associated with severe drug-drug interactions with concomitant medications that may contribute to death ( 35 ). Interestingly, we found an increased relative risk for death associated with DRV/c in older patients (more likely taking other drugs), in patients who experienced at hospital highest degree of COVID-19 severity (more likely taking other drugs) and in patients taking hydroxychloroquine, tocilizumab, sarilumab, remdesivir, or corticosteroids.…”

Drug Repurposing Against SARS-CoV-1, SARS-CoV-2 and MERS-CoV

“…Clinical efficacy of a 5-day treatment by the combination Darunavir/cobicistat was assessed and did not show any benefit compared to the standard of care [ 86 ]. Adverse events are controversial according to the studies, one of them showing that it was associated with negative outcomes in HIV-negative patients with severe COVID-19 pneumonia [ 86 , 87 ].…”

Evidence of the Clinical Efficacy of Antiviral Agents against SARS-CoV-2

“…Meanwhile, only two clinical studies have reported on the effects of DRV/c, and both indicated no significant evidence of improvement with DVR/c [55] (Table 5). In fact, this combination may be dangerous when treating hospitalized COVID-19 patients, as an exploratory retrospective study emphasized its lack of efficacy and highlighted the higher ventilation and mortality rates compared to controls [56].…”