A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19

Open label RCT (n=199) found no benefit with lopinavir–ritonavir treatment beyond standard care in hospitalized adult patients with severe Covid-19, in time to clinical improvement, 28 day mortality and percentages of patients with detectable viral RNA at various time points.

SPS commentary:

An editorial discusses why lopinavir–ritonavir isn’t effective; noting that two major factors may be in play. First, the authors chose a particularly challenging population. Second, lopinavir simply isn’t particularly potent against SARS-CoV-2. The concentration necessary to inhibit viral replication is relatively high as compared with the serum levels found in patients treated with lopinavir–ritonavir and currently know little about drug concentrations in the tissues where SARS-CoV-2 is replicating. Also the fact that this trial began within days after the virus was identified and that testing for infection was developed and deployed very rapidly means that test characteristics had not been fully defined. Notably, 35% of those who screened positive for SARS-CoV-2 by nasopharyngeal swab then tested negative at the day 1 visit by oropharyngeal swab. It concludes that despite the fact that lopinavir–ritonavir does not seem to be highly effective in patients with Covid-19, there are many important takeaways from this study. The investigators appropriately prioritized speed, designing a trial that could rapidly produce an answer and what has been learned from their work can help inform the design of new trials.


New England Journal of Medicine

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