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Viruses 2018, 10(11), 610; https://doi.org/10.3390/v10110610

Combination Therapy with Oseltamivir and Favipiravir Delays Mortality but Does Not Prevent Oseltamivir Resistance in Immunodeficient Mice Infected with Pandemic A(H1N1) Influenza Virus

Research Center in Infectious Diseases of the CHU of Québec and Laval University, 2705, Boul. Laurier (RC-709), Québec City, QC G1V 4G2, Canada
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Received: 28 September 2018 / Revised: 29 October 2018 / Accepted: 2 November 2018 / Published: 3 November 2018
(This article belongs to the Special Issue What’s New with Flu?)
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Abstract

Immunosuppressed individuals can shed influenza virus for prolonged periods of time, leading to the frequent emergence of antiviral resistance. We evaluated the benefits of oseltamivir and favipiravir combination therapy compared to single antiviral agents and monitored the emergence of drug-resistant variants in a pharmacologically immunosuppressed mouse model infected with the A(H1N1) pandemic influenza virus. C57BL/6 mice were immunosuppressed with cyclophosphamide and infected with a lethal dose of pandemic influenza A(H1N1) virus. Forty-eight hours post-infection, mice were treated with oseltamivir (20 mg/kg), favipiravir (20 or 50 mg/kg) or both agents BID for 5 or 10 days. Body weight losses, survival rates, lung viral titers, cytokine levels and emergence of resistant viruses were evaluated. Treatment of immunosuppressed mice with high (50 mg/kg) but not low (20 mg/kg) doses of favipiravir in combination with oseltamivir (20 mg/kg) significantly delayed mortality and reduced lung viral titers compared to treatment with a single drug regimen with oseltamivir but did not prevent the emergence of oseltamivir-resistant H275Y neuraminidase variants. Combination therapy with oseltamivir and favipiravir should be considered for evaluation in clinical trials. View Full-Text
Keywords: pandemic influenza virus; immunosuppression; combination therapy; oseltamivir; favipiravir; resistance; mice pandemic influenza virus; immunosuppression; combination therapy; oseltamivir; favipiravir; resistance; mice
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Baz, M.; Carbonneau, J.; Rhéaume, C.; Cavanagh, M.-H.; Boivin, G. Combination Therapy with Oseltamivir and Favipiravir Delays Mortality but Does Not Prevent Oseltamivir Resistance in Immunodeficient Mice Infected with Pandemic A(H1N1) Influenza Virus. Viruses 2018, 10, 610.

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