Darunavir-cobicistat versus lopinavir-ritonavir in the treatment of COVID-19 infection (DOLCI): A multicenter observational study

Abstract

Background Coronavirus Disease 2019 (COVID-19) is an evolving pandemic that urged the need to investigate various antiviral therapies. This study was conducted to compare efficacy and safety outcomes of darunavir-cobicistat versus lopinavir-ritonavir in treating patients with COVID-19 pneumonia. Methods and findings This retrospective, multicenter, observational study was conducted on adult patients hospitalized in one of the COVID-19 facilities in Qatar. Patients were included if they received darunavir-cobicistat or lopinavir-ritonavir for at least three days as part of their COVID-19 treatments. Data were collected from patients’ electronic medical records. The primary outcome was a composite endpoint of time to clinical improvement and/or virological clearance. Descriptive and inferential statistics were used at alpha level of 0.05. A total of 400 patients was analyzed, of whom 100 received darunavir-cobicistat and 300 received lopinavir-ritonavir. Majority of patients were male (92.5%), with a mean (SD) time from symptoms onset to start of therapy of 7.57 days (4.89). Patients received lopinavir-ritonavir had significantly faster time to clinical improvement and/or virological clearance than patients received darunavir-cobicistat (4 days [IQR 3–7] vs. 6.5 days [IQR 4–12]; HR 1.345 [95%CI: 1.070–1.691], P = 0.011). Patients received lopinavir-ritonavir had significantly faster time to clinical improvement (5 days [IQR 3–8] vs. 8 days [IQR 4–13]; HR 1.520 (95%CI: 1.2–1.925), P = 0.000), and slower time to virological clearance than darunavir-cobicistat (25 days [IQR 15–33] vs. 21 days [IQR 12.8–30]; HR 0.772 (95%CI: 0.607–0.982), P = 0.035). No significant difference in the incidence or severity of adverse events between groups. The study was limited to its retrospective nature and the possibility of covariates, which was accounted for by multivariate analyses. Conclusion In patients with COVID-19 pneumonia, early treatment with lopinavir-ritonavir was associated with faster time to clinical improvement and/or virological clearance than darunavir-cobicistat. Future trials are warranted to confirm these findings. Trial registration ClinicalTrials.gov number, NCT04425382.

Lopinavir-ritonavir versus darunavir-ritonavir for hospitalized COVID-19 patients

“…Additionally, a subgroup analysis of data from this study showed a lower risk of death in patients with mild disease treated with LPV/r [38]. Another observational study comparing the e cacy of early administered DRV/c versus LPV/r unravelled that LPV/r was associated with faster time to recovery and virological clearance, but not DRV/c [39]. These ndings can be also attributed to the unfavourable toxic side-effects of DRV/c [40].…”

COVID‐19: An Overview of SARS‐CoV‐2 Variants—The Current Vaccines and Drug Development

“…A small randomized clinical trial in China involving mild COVID-19 patients treated with darunavir/cobicistat for five days on top of interferon-alpha 2b inhalation or interferon alpha 2b inhalation alone did not demonstrate any increase in the proportion of negative conversion compared to standard of care alone [ 123 ]. Also, an observational study in Qatar involving adult patients hospitalized for COVID-19 found that early treatment with lopinavir-ritonavir resulted in faster clinical improvement and/or virological clearance than darunavir/cobicistat [ 125 ]. Furthermore, a large cohort study of Italian patients hospitalized in 33 hospitals found that while the use of lopinavir/ritonavir did not change the death rate, the use of darunavir/cobicistat increased mortality [ 126 ].…”

Drugs for COVID-19: An Update

“…An updated systematic review examined whether the use of LPV/r could be more favorable compared to the standard therapies regarding the length of stay, time for positive-to-negative conversion of SARS-CoV-2 and mortality in hospitalized patients with COVID-19, concluding that LPV/r had no significant advantage and also registered a significant increase in the occurrence of side effects [ 40 ]. However, Elmekaty et al [ 41 ] showed that early treatment with LPV/r is associated with a faster clinical improvement and/or virological clearance than the darunavir/cobicistat therapy in patients with COVID-19 pneumonia, and that the safety profile was quite comparable. Finally, Wong et al [ 42 ] discourage the use of LPV/r for pediatric COVID-19 cases because of their negative clinical outcomes, reporting a longer time for clinical improvement, seroconversion, hospital discharge, together with a higher risk of a hyperinflammation.…”