A Trial of Lopinavir–Ritonavir in Covid-19

To the Editor: After a review of the findings of Cao et al. (published in the Journal online on March 18),1 many clinicians are abandoning the use of lopinavir–ritonavir for the treatment of Covid-19. We consider this action to be premature. It is crucial to realize that although this trial did not show that the time until clinical improvement was meaningfully better than standard care among patients with severe Covid-19 who received lopinavir–ritonavir, the trial was statistically underpowered to show this outcome. In addition, the analyses of secondary outcomes (which still require confirmation) suggested that lopinavir–ritonavir may be associated with substantial lowering of overall mortality (19% in patients in the lopinavir–ritonavir group vs. 25% in the standard-care group), the risk of severe adverse events (20% vs. 32%), and the risk of respiratory failure or acute respiratory distress syndrome (13% vs. 27%). Lopinavir–ritonavir has shown activity against SARS-CoV-12,3 and is available for immediate clinical use in many countries. Because there currently are no approved treatments for Covid-19,4 and because the pandemic diffusion of SARS-CoV-2 is causing shortages of alternative drugs, we should not yet abandon lopinavir–ritonavir. We therefore advocate that therapeutic guidelines retain lopinavir–ritonavir as a treatment option against Covid-19, pending completion of the World Health Organization SOLIDARITY trial.5