{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:38:56Z","timestamp":1790419136059,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2018,11,3]],"date-time":"2018-11-03T00:00:00Z","timestamp":1541203200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["229733"],"award-info":[{"award-number":["229733"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/v10110610","type":"journal-article","created":{"date-parts":[[2018,11,5]],"date-time":"2018-11-05T10:43:45Z","timestamp":1541414625000},"page":"610","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Combination Therapy with Oseltamivir and Favipiravir Delays Mortality but Does Not Prevent Oseltamivir Resistance in Immunodeficient Mice Infected with Pandemic A(H1N1) Influenza Virus"],"prefix":"10.3390","volume":"10","author":[{"given":"Mariana","family":"Baz","sequence":"first","affiliation":[{"name":"Research Center in Infectious Diseases of the CHU of Qu\u00e9bec and Laval University, 2705, Boul. Laurier (RC-709), Qu\u00e9bec City, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Carbonneau","sequence":"additional","affiliation":[{"name":"Research Center in Infectious Diseases of the CHU of Qu\u00e9bec and Laval University, 2705, Boul. Laurier (RC-709), Qu\u00e9bec City, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Rh\u00e9aume","sequence":"additional","affiliation":[{"name":"Research Center in Infectious Diseases of the CHU of Qu\u00e9bec and Laval University, 2705, Boul. Laurier (RC-709), Qu\u00e9bec City, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-H\u00e9l\u00e8ne","family":"Cavanagh","sequence":"additional","affiliation":[{"name":"Research Center in Infectious Diseases of the CHU of Qu\u00e9bec and Laval University, 2705, Boul. Laurier (RC-709), Qu\u00e9bec City, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Boivin","sequence":"additional","affiliation":[{"name":"Research Center in Infectious Diseases of the CHU of Qu\u00e9bec and Laval University, 2705, Boul. Laurier (RC-709), Qu\u00e9bec City, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,11,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1182\/blood-2009-11-255455","article-title":"How I treat influenza in patients with hematologic malignancies","volume":"115","author":"Casper","year":"2010","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1001\/archinte.161.3.441","article-title":"Excess mortality due to pneumonia or influenza during influenza seasons among persons with acquired immunodeficiency syndrome","volume":"161","author":"Lin","year":"2001","journal-title":"Arch. Intern. 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