Combination Therapy With Neuraminidase and Polymerase Inhibitors in Nude Mice Infected With Influenza Virus.
J Infect Dis
; 217(6): 887-896, 2018 03 05.
Article
em En
| MEDLINE
| ID: mdl-29186472
ABSTRACT
Background:
Treatment of immunocompromised, influenza virus-infected patients with the viral neuraminidase inhibitor oseltamivir often leads to the emergence of drug-resistant variants. Combination therapy with compounds that target different steps in the viral life cycle may improve treatment outcomes and reduce the emergence of drug-resistant variants.Methods:
Here, we infected immunocompromised nude mice with an influenza A virus and treated them with neuraminidase (oseltamivir, laninamivir) or viral polymerase (favipiravir) inhibitors, or combinations thereof.Results:
Combination therapy for 28 days increased survival times compared with monotherapy, but the animals died after treatment was terminated. Mono- and combination therapies did not consistently reduce lung virus titers. Prolonged viral replication led to the emergence of neuraminidase inhibitor-resistant variants, although viruses remained sensitive to favipiravir. Overall, favipiravir provided greater benefit than neuraminidase inhibitors.Conclusions:
Collectively, our data demonstrate that combination therapy in immunocompromised hosts increases survival times, but does not suppress the emergence of neuraminidase inhibitor-resistant variants.
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Base de dados:
MEDLINE
Assunto principal:
Pirazinas
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Infecções por Orthomyxoviridae
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Inibidores Enzimáticos
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Vírus da Influenza A Subtipo H1N1
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Oseltamivir
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Zanamivir
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Amidas
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article