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Antiviral Combo Fails to Help in Covid-19

Wednesday, March 25, 2020 // Uncategorized

The following is a summary from Journal Watch, a publication which provides summaries of important medical studies from AUTHORITATIVE medical journals around the world. The reason authoritative was in CAPS is that a lot of the articles that patients send me are from obscure journals that I’ve never heard of or articles that have never even been published. This study is from the most recent New England Journal of Medicine (NEJM) which is considered one of the best. This is a small study which needs to be confirmed in a larger study which is planned. It is an open label study. This means that it was not blinded. Both the participants and researchers knew who was taking the drug combination. It was randomized. Half the patients were assigned by chance to one group and half to the other.
March 24, 2020

Lopinavir-Ritonavir Was Not Effective for COVID-19
Neil M. Ampel, MD reviewing Cao B et al. N Engl J Med 2020 Mar 18 Baden LR and Rubin EJ. N Engl J Med 2020 Mar 18

In an open-label randomized study in Wuhan, China, 14 days of lopinavir-ritonavir therapy did not differ from standard care regarding clinical improvement or decrease in viral RNA load.

Currently, there are no drugs documented to be effective to treat patients with COVID-19 arising from coronavirus SARS-CoV-2 infection. However, lopinavir (a protease inhibitor clinically available for HIV-1 infection) has shown in vitro activity against SARS-CoV, and a study of lopinavir plus the protease inhibitor ritonavir demonstrated clinical efficacy for human severe acute respiratory syndrome (SARS). To evaluate whether lopinavir-ritonavir would be effective for COVID-19, investigators conducted an open-label randomized trial at a single hospital in Wuhan, China, beginning on January 18, 2020. They assigned 199 adult patients with SARS-CoV-2 infection, radiographically confirmed pneumonia, and an oxygen saturation of <94% or a partial pressure of oxygen <300 mm Hg to receive standard care alone or with oral lopinavir-ritonavir (400 mg–100 mg) twice daily for 14 days.

Lopinavir-ritonavir recipients and those receiving standard care did not differ significantly in time to clinical improvement (median, 16 days), duration of intensive care unit stay, days of mechanical ventilation, or days of oxygen support. Patients who received lopinavir-ritonavir had lower 28-day mortality (19% vs. 25%), but the between-group difference was not significant. SARS-CoV-2 RNA concentrations in throat swabs obtained over time did not differ between the two groups.

COMMENT
This swiftly performed, well-executed study should serve as a model for other therapeutic trials aimed at the ongoing pandemic. As editorialists note, lopinavir-ritonavir is broadly available and, if it had been demonstrably effective, would have represented an immediate oral therapy for COVID-19. Unfortunately, that was not the case. While mortality was somewhat lower with this medication, the effect was neither striking nor significant. Despite these results, the WHO is launching a large study that includes lopinavir-ritonavir in one of the arms (Science 2020 Mar 22; [e-pub]). However, based on the structure of the SARS-CoV-2 protease, many experts in the field think HIV protease inhibitors are unlikely to be active.

EDITOR DISCLOSURES AT TIME OF PUBLICATION
Disclosures for Neil M. Ampel, MD at time of publication
Leadership Positions in Professional Societies Coccidioidomycosis Study Group (President)
CITATION(S):
Cao B et al. Lopinavir–ritonavir in adults hospitalized with severe Covid-19. N Engl J Med 2020 Mar 18; [e-pub]. (https://doi.org/10.1056/NEJMoa2001282)

Baden LR and Rubin EJ. Covid-19 — The search for effective therapy. N Engl J Med 2020 Mar 18; [e-pub]. (https://doi.org/10.1056/NEJMe2005477)

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