Impact of different oseltamivir regimens on treating influenza A virus infection and resistance emergence: insights from a modelling study.

Several studies have proven oseltamivir to be efficient in reducing influenza viral titer and symptom intensity. However, the usefulness of oseltamivir can be compromised by the emergence and spread of drug-resistant virus. The selective pressure exerted by different oseltamivir therapy regimens hav...

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Autores principales:	Laetitia Canini, Jessica M Conway, Alan S Perelson, Fabrice Carrat
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/f2ebde7008224f69b26c31cf4112a0fa
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spelling	oai:doaj.org-article:f2ebde7008224f69b26c31cf4112a0fa2021-11-18T05:52:57ZImpact of different oseltamivir regimens on treating influenza A virus infection and resistance emergence: insights from a modelling study.1553-734X1553-735810.1371/journal.pcbi.1003568https://doaj.org/article/f2ebde7008224f69b26c31cf4112a0fa2014-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24743564/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Several studies have proven oseltamivir to be efficient in reducing influenza viral titer and symptom intensity. However, the usefulness of oseltamivir can be compromised by the emergence and spread of drug-resistant virus. The selective pressure exerted by different oseltamivir therapy regimens have received little attention. Combining models of drug pharmacokinetics, pharmacodynamics, viral kinetics and symptom dynamics, we explored the efficacy of oseltamivir in reducing both symptoms (symptom efficacy) and viral load (virological efficacy). We simulated samples of 1000 subjects using previously estimated between-subject variability in viral and symptom dynamic parameters to describe the observed heterogeneity in a patient population. We simulated random mutations conferring resistance to oseltamivir. We explored the effect of therapy initiation time, dose, intake frequency and therapy duration on influenza infection, illness dynamics, and emergence of viral resistance. Symptom and virological efficacies were strongly associated with therapy initiation time. The proportion of subjects shedding resistant virus was 27-fold higher when prophylaxis was initiated during the incubation period compared with no treatment. It fell to below 1% when treatment was initiated after symptom onset for twice-a-day intakes. Lower doses and prophylaxis regimens led to lower efficacies and increased risk of resistance emergence. We conclude that prophylaxis initiated during the incubation period is the main factor leading to resistance emergence.Laetitia CaniniJessica M ConwayAlan S PerelsonFabrice CarratPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 10, Iss 4, p e1003568 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Laetitia Canini Jessica M Conway Alan S Perelson Fabrice Carrat Impact of different oseltamivir regimens on treating influenza A virus infection and resistance emergence: insights from a modelling study.
description	Several studies have proven oseltamivir to be efficient in reducing influenza viral titer and symptom intensity. However, the usefulness of oseltamivir can be compromised by the emergence and spread of drug-resistant virus. The selective pressure exerted by different oseltamivir therapy regimens have received little attention. Combining models of drug pharmacokinetics, pharmacodynamics, viral kinetics and symptom dynamics, we explored the efficacy of oseltamivir in reducing both symptoms (symptom efficacy) and viral load (virological efficacy). We simulated samples of 1000 subjects using previously estimated between-subject variability in viral and symptom dynamic parameters to describe the observed heterogeneity in a patient population. We simulated random mutations conferring resistance to oseltamivir. We explored the effect of therapy initiation time, dose, intake frequency and therapy duration on influenza infection, illness dynamics, and emergence of viral resistance. Symptom and virological efficacies were strongly associated with therapy initiation time. The proportion of subjects shedding resistant virus was 27-fold higher when prophylaxis was initiated during the incubation period compared with no treatment. It fell to below 1% when treatment was initiated after symptom onset for twice-a-day intakes. Lower doses and prophylaxis regimens led to lower efficacies and increased risk of resistance emergence. We conclude that prophylaxis initiated during the incubation period is the main factor leading to resistance emergence.
format	article
author	Laetitia Canini Jessica M Conway Alan S Perelson Fabrice Carrat
author_facet	Laetitia Canini Jessica M Conway Alan S Perelson Fabrice Carrat
author_sort	Laetitia Canini
title	Impact of different oseltamivir regimens on treating influenza A virus infection and resistance emergence: insights from a modelling study.
title_short	Impact of different oseltamivir regimens on treating influenza A virus infection and resistance emergence: insights from a modelling study.
title_full	Impact of different oseltamivir regimens on treating influenza A virus infection and resistance emergence: insights from a modelling study.
title_fullStr	Impact of different oseltamivir regimens on treating influenza A virus infection and resistance emergence: insights from a modelling study.
title_full_unstemmed	Impact of different oseltamivir regimens on treating influenza A virus infection and resistance emergence: insights from a modelling study.
title_sort	impact of different oseltamivir regimens on treating influenza a virus infection and resistance emergence: insights from a modelling study.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/f2ebde7008224f69b26c31cf4112a0fa
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Impact of different oseltamivir regimens on treating influenza A virus infection and resistance emergence: insights from a modelling study.

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