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

Eman Zeyad I Elmekaty, Rim Alibrahim, Rania Hassanin, Sitelbanat Eltaib, Ahmed Elsayed, Fatima Rustom, Mohamed Izham Mohamed Ibrahim, Mohammed Abu Khattab, Hussam Al Soub, Muna Al Maslamani, Abdullatif Al-Khal, Eman Zeyad I Elmekaty, Rim Alibrahim, Rania Hassanin, Sitelbanat Eltaib, Ahmed Elsayed, Fatima Rustom, Mohamed Izham Mohamed Ibrahim, Mohammed Abu Khattab, Hussam Al Soub, Muna Al Maslamani, Abdullatif Al-Khal

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.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Kaplan-Meier curve for the time…
Fig 1. Kaplan-Meier curve for the time to primary outcomes.
(A) Time to clinical improvement. (B) Time to viral clearance. (C) Time to first composite of primary outcome.

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