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Viruses 2017, 9(8), 197; doi:10.3390/v9080197

The Mechanisms for Within-Host Influenza Virus Control Affect Model-Based Assessment and Prediction of Antiviral Treatment

1
School of Mathematics and Statistics, The University of Melbourne, Melbourne, Victoria 3010, Australia
2
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria 3010, Australia
3
Modelling and Simulation, Infection and Immunity Theme, Murdoch Childrens Research Institute, The Royal Children’s Hospital, Parkville, Victoria 3052, Australia
*
Author to whom correspondence should be addressed.
Academic Editors: John Murray and Ruy Ribeiro
Received: 30 June 2017 / Revised: 18 July 2017 / Accepted: 24 July 2017 / Published: 26 July 2017
(This article belongs to the Special Issue Mathematical Modeling of Viral Infections)
View Full-Text   |   Download PDF [948 KB, uploaded 26 July 2017]   |  

Abstract

Models of within-host influenza viral dynamics have contributed to an improved understanding of viral dynamics and antiviral effects over the past decade. Existing models can be classified into two broad types based on the mechanism of viral control: models utilising target cell depletion to limit the progress of infection and models which rely on timely activation of innate and adaptive immune responses to control the infection. In this paper, we compare how two exemplar models based on these different mechanisms behave and investigate how the mechanistic difference affects the assessment and prediction of antiviral treatment. We find that the assumed mechanism for viral control strongly influences the predicted outcomes of treatment. Furthermore, we observe that for the target cell-limited model the assumed drug efficacy strongly influences the predicted treatment outcomes. The area under the viral load curve is identified as the most reliable predictor of drug efficacy, and is robust to model selection. Moreover, with support from previous clinical studies, we suggest that the target cell-limited model is more suitable for modelling in vitro assays or infection in some immunocompromised/immunosuppressed patients while the immune response model is preferred for predicting the infection/antiviral effect in immunocompetent animals/patients. View Full-Text
Keywords: model selection; target cell depletion; immune response; neuraminidase inhibitor; drug efficacy model selection; target cell depletion; immune response; neuraminidase inhibitor; drug efficacy
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Cao, P.; McCaw, J.M. The Mechanisms for Within-Host Influenza Virus Control Affect Model-Based Assessment and Prediction of Antiviral Treatment. Viruses 2017, 9, 197.

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