Analyse et modélisation de l'effet de l'interleukine 7 sur les patients infectés par le VIH

Abstract : In HIV infected patients, antiretroviral therapy suppresses the viral replication which is followed in most patients by a restoration of the CD4+ T cells (CD4) pool. However, it is not the case for some patients called low immunological responders. Injections of interleukin-7 (IL7), a cytokine involved in the CD4 homeostasis, are considered in order to maintain the CD4 levels above 500 cells per microL, the level at which life expectancy is similar to that of the non-infected. INSPIRE trials evaluated the effect of repeated injections of IL7 on low immunological responders. We present a few mechanistic models of the effect of IL7 injections on CD4, which include random effects to account for inter-individual variability. Using these models with a Bayesian approach, the individual parameters of a new patient are sampled, which allows us to make predictions about its CD4 dynamics and thus to personalize the treatment. We propose four adaptive protocols that limit the time spent under 500 CD4 per microL, without increasing the number of injections. Those protocols are implemented into a Shiny app with an easy to use interface, and they could be tested during clinical trials. The viral reservoir, mainly made up of quiescent infected CD4, is the main obstacle to HIV eradication. IL7 injections induce an increase of the level of CD4, hence of the viral reservoir ; the question is then to determine if the injections induce new cell infections or if the reservoir increases in the same way as CD4. We conclude that while some patients presented marker dynamics consistent with the occurrence of new cell infections, this is not the case for the majority of patients. Confirmation of these events and characterization of potential at-risk patients requires additional measurable data in a clinical trial.
Document type :
Theses
Liste complète des métadonnées

https://hal.inria.fr/tel-01973123
Contributor : Laura Villain <>
Submitted on : Tuesday, January 8, 2019 - 10:38:37 AM
Last modification on : Wednesday, January 9, 2019 - 1:21:18 AM
Document(s) archivé(s) le : Tuesday, April 9, 2019 - 2:07:56 PM

File

these_laura_villain.pdf
Files produced by the author(s)

Identifiers

  • HAL Id : tel-01973123, version 1

Collections

Citation

Laura Villain. Analyse et modélisation de l'effet de l'interleukine 7 sur les patients infectés par le VIH. Applications [stat.AP]. Université de bordeaux, 2018. Français. ⟨tel-01973123⟩

Share

Metrics

Record views

71

Files downloads

89