Comparative efficacy of repurposed drugs lopinavir-ritonavir and darunavir-ritonavir in hospitalised COVID-19 patients: insights from a tertiary centre cohort
BackgroundDrug repurposing has become a widely adopted strategy to minimise research time, costs, and associated risks. Combinations of protease inhibitors such as lopinavir and darunavir with ritonavir have been repurposed as treatments for COVID-19. Although lopinavir-ritonavir (LPV/r) and darunav...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2024.1496176/full |
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| author | Dóra Paróczai Dóra Paróczai András Bikov András Bikov Andreea Blidaru Emanuel Bobu Ana Lascu Ana Lascu Cristian Ion Mot Cristian Ion Mot Stefan Mihaicuta Stefan Mihaicuta Stefan Frent Stefan Frent |
| author_facet | Dóra Paróczai Dóra Paróczai András Bikov András Bikov Andreea Blidaru Emanuel Bobu Ana Lascu Ana Lascu Cristian Ion Mot Cristian Ion Mot Stefan Mihaicuta Stefan Mihaicuta Stefan Frent Stefan Frent |
| author_sort | Dóra Paróczai |
| collection | DOAJ |
| description | BackgroundDrug repurposing has become a widely adopted strategy to minimise research time, costs, and associated risks. Combinations of protease inhibitors such as lopinavir and darunavir with ritonavir have been repurposed as treatments for COVID-19. Although lopinavir-ritonavir (LPV/r) and darunavir-ritonavir (DRV/r) have shown in vitro efficacy against COVID-19, the results in human studies have been inconsistent. Therefore, our objective was to compare the efficacy of LPV/r and DRV/r in COVID-19 patients admitted to a tertiary centre in Romania.Research design and methodsA clinical dataset from 417 hospitalised patients was analysed. Patients were assigned to the LPV/r, DRV/r, or control (standard-of-care) group based on clinical decisions made by the attending infectious disease specialists, aligned with national treatment protocols. Kaplan-Meier and Cox proportional hazards regression analyses were conducted to compare in-hospital mortality and to identify factors associated with clinical improvement or fatal outcomes.ResultsBy day 10, more patients showed improvement with LPV/r and DRV/r (p=0.03 and 0.01, respectively), but only LPV/r was associated with improved survival compared to the control group (p=0.05). Factors associated with mortality included male gender (HR: 3.63, p=0.02), diabetes (HR: 2.49, p=0.03), oxygen saturation below 90% at admission (HR: 5.23, p<0.01), high blood glucose levels (HR: 3.68, p=0.01), age (HR: 1.04, p=0.02), and more than 25% lesion extension on chest CT scan (HR: 2.28, p=0.03).ConclusionsLPV/r, but not DRV/r, showed a survival benefit in patients hospitalised with COVID-19, but these findings deserve further investigation in a randomised clinical trial. |
| format | Article |
| id | doaj-art-d8a7a53111c047d5a66f5469f69e12cc |
| institution | Kabale University |
| issn | 2235-2988 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj-art-d8a7a53111c047d5a66f5469f69e12cc2025-01-16T06:10:51ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-01-011410.3389/fcimb.2024.14961761496176Comparative efficacy of repurposed drugs lopinavir-ritonavir and darunavir-ritonavir in hospitalised COVID-19 patients: insights from a tertiary centre cohortDóra Paróczai0Dóra Paróczai1András Bikov2András Bikov3Andreea Blidaru4Emanuel Bobu5Ana Lascu6Ana Lascu7Cristian Ion Mot8Cristian Ion Mot9Stefan Mihaicuta10Stefan Mihaicuta11Stefan Frent12Stefan Frent13Department of Medical Microbiology, University of Szeged, Szeged, HungaryAlbert Szent-Györgyi Health Center, Pulmonology Clinic, University of Szeged, Deszk, HungaryNorth West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, United KingdomDivision of Immunology, Immunity to Infection and Respiratory Medicine, University of Manchester, Manchester, United KingdomDepartment of Infectious Diseases, Infectious Diseases and Pulmonology Clinical Hospital, Timisoara, RomaniaDepartment of Pulmonology, University of Medicine and Pharmacy Timisoara, Timisoara, RomaniaDepartment of Functional Sciences, Discipline of Pathophysiology, Centre for Translational Research and Systems Medicine, University of Medicine and Pharmacy Timisoara, Timisoara, RomaniaInstitute for Cardiovascular Diseases of Timisoara, Clinic for Cardiovascular Surgery, Timisoara, RomaniaENT Department, Municipal Emergency Hospital Timisoara, Timisoara, Romania0Department of Surgery, University of Medicine and Pharmacy Timisoara, Timisoara, RomaniaDepartment of Infectious Diseases, Infectious Diseases and Pulmonology Clinical Hospital, Timisoara, Romania1Centre for Research and Innovation in Precision Medicine of Respiratory Diseases, Department of Pulmonology, University of Medicine and Pharmacy Timisoara, Timisoara, RomaniaDepartment of Infectious Diseases, Infectious Diseases and Pulmonology Clinical Hospital, Timisoara, Romania1Centre for Research and Innovation in Precision Medicine of Respiratory Diseases, Department of Pulmonology, University of Medicine and Pharmacy Timisoara, Timisoara, RomaniaBackgroundDrug repurposing has become a widely adopted strategy to minimise research time, costs, and associated risks. Combinations of protease inhibitors such as lopinavir and darunavir with ritonavir have been repurposed as treatments for COVID-19. Although lopinavir-ritonavir (LPV/r) and darunavir-ritonavir (DRV/r) have shown in vitro efficacy against COVID-19, the results in human studies have been inconsistent. Therefore, our objective was to compare the efficacy of LPV/r and DRV/r in COVID-19 patients admitted to a tertiary centre in Romania.Research design and methodsA clinical dataset from 417 hospitalised patients was analysed. Patients were assigned to the LPV/r, DRV/r, or control (standard-of-care) group based on clinical decisions made by the attending infectious disease specialists, aligned with national treatment protocols. Kaplan-Meier and Cox proportional hazards regression analyses were conducted to compare in-hospital mortality and to identify factors associated with clinical improvement or fatal outcomes.ResultsBy day 10, more patients showed improvement with LPV/r and DRV/r (p=0.03 and 0.01, respectively), but only LPV/r was associated with improved survival compared to the control group (p=0.05). Factors associated with mortality included male gender (HR: 3.63, p=0.02), diabetes (HR: 2.49, p=0.03), oxygen saturation below 90% at admission (HR: 5.23, p<0.01), high blood glucose levels (HR: 3.68, p=0.01), age (HR: 1.04, p=0.02), and more than 25% lesion extension on chest CT scan (HR: 2.28, p=0.03).ConclusionsLPV/r, but not DRV/r, showed a survival benefit in patients hospitalised with COVID-19, but these findings deserve further investigation in a randomised clinical trial.https://www.frontiersin.org/articles/10.3389/fcimb.2024.1496176/fullCOVID-19darunavirlopinavirpropensity score matchingritonavir |
| spellingShingle | Dóra Paróczai Dóra Paróczai András Bikov András Bikov Andreea Blidaru Emanuel Bobu Ana Lascu Ana Lascu Cristian Ion Mot Cristian Ion Mot Stefan Mihaicuta Stefan Mihaicuta Stefan Frent Stefan Frent Comparative efficacy of repurposed drugs lopinavir-ritonavir and darunavir-ritonavir in hospitalised COVID-19 patients: insights from a tertiary centre cohort Frontiers in Cellular and Infection Microbiology COVID-19 darunavir lopinavir propensity score matching ritonavir |
| title | Comparative efficacy of repurposed drugs lopinavir-ritonavir and darunavir-ritonavir in hospitalised COVID-19 patients: insights from a tertiary centre cohort |
| title_full | Comparative efficacy of repurposed drugs lopinavir-ritonavir and darunavir-ritonavir in hospitalised COVID-19 patients: insights from a tertiary centre cohort |
| title_fullStr | Comparative efficacy of repurposed drugs lopinavir-ritonavir and darunavir-ritonavir in hospitalised COVID-19 patients: insights from a tertiary centre cohort |
| title_full_unstemmed | Comparative efficacy of repurposed drugs lopinavir-ritonavir and darunavir-ritonavir in hospitalised COVID-19 patients: insights from a tertiary centre cohort |
| title_short | Comparative efficacy of repurposed drugs lopinavir-ritonavir and darunavir-ritonavir in hospitalised COVID-19 patients: insights from a tertiary centre cohort |
| title_sort | comparative efficacy of repurposed drugs lopinavir ritonavir and darunavir ritonavir in hospitalised covid 19 patients insights from a tertiary centre cohort |
| topic | COVID-19 darunavir lopinavir propensity score matching ritonavir |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2024.1496176/full |
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