Understanding the within-host dynamics of influenza A virus: from theory to clinical implications.
Mathematical models have provided important insights into acute viral dynamics within individual patients. In this paper, we study the simplest target cell-limited models to investigate the within-host dynamics of influenza A virus infection in humans. Despite the biological simplicity of the models, we show how these can be used to understand the severity of the infection and the key attributes of possible immunotherapy and antiviral drugs for the treatment of infection at different times post infection. Through an analytic approach, we derive and estimate simple summary biological quantities that can provide novel insights into the infection dynamics and the definition of clinical endpoints. We focus on nine quantities, including the area under the viral load curve, peak viral load, the time to peak viral load and the level of cell death due to infection. Using Markov chain Monte Carlo methods, we fitted the models to data collected from 12 untreated volunteers who participated in two clinical studies that tested the antiviral drugs oseltamivir and zanamivir. Based on the results, we also discuss various difficulties in deriving precise estimates of the parameters, even in the very simple models considered, when experimental data are limited to viral load measures and/or there is a limited number of viral load measurements post infection.
Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, UK c.hadjichrysanthou@imperial.ac.uk.
Christoforos
0000-0001-6166-5899
C
Hadjichrysanthou
Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, UK.
Emilie
E
Cauët
Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, UK.
Emma
E
Lawrence
Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, UK.
Carolin
C
Vegvari
Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, UK Janssen Prevention Center, Leiden, The Netherlands.
Frank
F
de Wolf
Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, UK.
Roy M
RM
Anderson
D000998:Antiviral Agents / Q000627:therapeutic use*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000188:drug therapy* / Q000276:immunology*; D018448:Models, Immunological; D053139:Oseltamivir / Q000652:urine*; D019562:Viral Load / Q000187:drug effects / Q000276:immunology
D000998:Antiviral Agents; D053139:Oseltamivir
acute viral infection; immune control; influenza A; viral kinetics; within-host modelling