title: Oseltamivir-zanamivir combination therapy is not superior to zanamivir monotherapy in mice infected with influenza A(H3N2) and A(H1N1)pdm09 viruses.
abstract: The efficacy of oseltamivir-zanamivir combination therapy compared to that of monotherapy was evaluated in mice infected with influenza A(H3N2) or A(H1N1)pdm09 viruses. For A(H3N2) virus, zanamivir monotherapy and oseltamivir-zanamivir combination showed significant reduction of mean weight loss compared to oseltamivir. Zanamivir monotherapy also conferred decreased mortality, weight loss and lung viral titers (LVT) compared to oseltamivir for A(H1N1)pdm09 wild-type virus. Intermediate benefits were observed for the oseltamivir-zanamivir combination. For the oseltamivir-resistant A(H1N1)pdm09 H275Y virus, the efficacy of oseltamivir-zanamivir was comparable to that of zanamivir and significantly higher than that of oseltamivir in terms of survival, weight loss and LVT.
authors.affiliation: Research Center in Infectious Diseases of the CHUQ-CHUL, Québec City, QC, Canada; Laval University, Québec City, QC, Canada.
authors.forename: Andrés
authors.initials: A
authors.lastname: Pizzorno
authors.affiliation: Research Center in Infectious Diseases of the CHUQ-CHUL, Québec City, QC, Canada; Laval University, Québec City, QC, Canada.
authors.forename: Yacine
authors.initials: Y
authors.lastname: Abed
authors.affiliation: Research Center in Infectious Diseases of the CHUQ-CHUL, Québec City, QC, Canada; Laval University, Québec City, QC, Canada.
authors.forename: Chantal
authors.initials: C
authors.lastname: Rhéaume
authors.affiliation: Research Center in Infectious Diseases of the CHUQ-CHUL, Québec City, QC, Canada; Laval University, Québec City, QC, Canada. Electronic address: Guy.Boivin@crchul.ulaval.ca.
authors.forename: Guy
authors.initials: G
authors.lastname: Boivin
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001835:Body Weight; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000379:methods; D053118:Influenza A Virus, H1N1 Subtype / Q000302:isolation & purification*; D053122:Influenza A Virus, H3N2 Subtype / Q000302:isolation & purification*; D008168:Lung / Q000821:virology; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000821:virology; D053139:Oseltamivir / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome; D019562:Viral Load; D053243:Zanamivir / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir; D053243:Zanamivir
keywords: Combination; Influenza; Neuraminidase inhibitors; Oseltamivir; Resistance; Zanamivir