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Modélisation dynamique de l'interaction hôte-pathogène appliquée à la primo-infection à VIH

Abstract : Primary HIV infection, which corresponds to the first weeks of infection, is a crucial phase which determines partly the clinical progression. The dynamics of HIV viral load and CD4 count during this phase is complex. First, as it is asymptotic in most of the cases, the primary HIV infection is not observed. Moreover, the date of infection is generally unknown and the evolution of markers with respect to the time of infection is difficult. Dynamical models based on systems of ordinary differential equations (ODE) allow to take into account complex non-linear between HIV and the immune system. Moreover, their mechanistic characteristic can be useful through the understanding of physiopathology or the effect of an intervention. However, the estimation of this kind of models is complex and several methods are currently available. We propose here a method of estimation for ODE models taking into account the uncertainty of the date of infection. This method is applied to real dataset of 761 seroconverters from the CASCADE Collaboration during their first year of follow-up. Dynamical models have many parameters on which we can include random effects and explanatory variables. The selection of the best model can be time-consuming if we consider the computation's time issues met during estimation. We develop score tests for exploring complex models with an application to HIV dynamics models. Finally, we compare different biological models of primary HIV infection to predict the dynamics of plasma viral load and CD4 count.
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https://tel.archives-ouvertes.fr/tel-00433430
Contributor : Julia Drylewicz <>
Submitted on : Thursday, November 19, 2009 - 12:37:15 PM
Last modification on : Friday, October 23, 2020 - 4:36:40 PM
Long-term archiving on: : Thursday, June 17, 2010 - 6:57:09 PM

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Julia Drylewicz. Modélisation dynamique de l'interaction hôte-pathogène appliquée à la primo-infection à VIH. Sciences du Vivant [q-bio]. Université Victor Segalen - Bordeaux II, 2009. Français. ⟨tel-00433430⟩

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