Plasma concentration and safety of lopinavir/ritonavir in patients with Covid-19: a retrospective cohort study

Chouchana, L.; Boujaafar, S.; Gana, I.; Preta, L.-H.; Regard, L.; Legendre, P.; Azoulay, C.; Canouï, E.; Zerbit, J.; Carlier, N.; Terrier, B.; Kerneis, S.; Batista, R.; Treluyer, J.-M.; Zheng, Y.; Benaboud, S.

Background: There is an urgent need of active treatment for coronavirus disease 2019 (Covid-19). Although efficacy have not been proven, lopinavir/ritonavir 400 mg/100 mg twice daily has been proposed as a treatment of moderate to severe Covid-19. Previously published cohorts showed Covid-19 is associated with major inflammation. To date, no data are available regarding lopinavir/ritonavir plasma concentration and its safety in Covid-19 patients. Methods: Real-world Covid-19 experience based on a retrospective cohort study Results: On the cohort of 31 patients treated by lopinavir/ritonavir for Covid-19, we observed very high lopinavir plasma concentrations, increased of 4.6-fold (IQR 2.9-6.4), with regards to average plasma concentrations in HIV treatment. All except two patients were above the upper limit of the concentration ranges of HIV treatment. In this cohort, about one over four to five patients prematurely stopped lopinavir/ritonavir therapy due to a moderate adverse drug reaction, mainly hepatic and gastrointestinal disorders. Conclusion: Patients with Covid-19 pneumonitis treated with lopinavir/ritonavir have plasma concentrations dramatically higher than expected. Owing to that high plasma concentration may be required for antiviral activity against SARS-CoV-2, it appears that lopinavir dosage should not be reduced in the absence of adverse effect. About 80% of the patients well tolerated lopinavir/ritonavir therapy under these plasma concentrations. However, cautious is necessary as drug repurposing can be associated with a new drug safety profile.