Controlling IL-7 injections in HIV-infected patients

DOI10.1007/S11538-018-0465-8zbMATH Open1400.92326arXiv1801.06227OpenAlexW2963667321WikidataQ90729938 ScholiaQ90729938MaRDI QIDQ1990146FDOQ1990146

Authors: Chloé Pasin, Laura Villain, Huilong Zhang, Rodolphe Thiébaut, F. Dufour 

Publication date: 24 October 2018

Published in: Bulletin of Mathematical Biology (Search for Journal in Brave)

Abstract: Immune interventions consisting in repeated injection are broadly used as they are thought to improve the quantity and the quality of the immune response. However, they also raised several questions that remains unanswered, in particular the number of injections to make or the delay to respect between different injections to acheive this goal. Practical and financial considerations add constraints to these questions, especially in the framework of human studies. We specifically focus here on the use of interleukine-7 (IL-7) injections in HIV-infected patients under antiretroviral treatment, but still unable to restore normal levels of CD4+ T lymphocytes. Clinical trials have already shown that repeated cycles of injections of IL-7 could help maintaining CD4+ T lymphocytes levels over the limit of 500 cells per microL, by affecting proliferation and survival of CD4+ T cells. We then aim at answering the question : how to maintain a patient's level of CD4+ T lymphocytes by using a minimum number of injections (ie optimizing the strategy of injections) ? Based on mechanistic models that were previously developed for the dynamics of CD4+ T lymphocytes in this context, we model the process by a piecewise deterministic Markov model. We then address the question by using some recently established theory on impulse control problem in order to develop a numerical tool determining the optimal strategy. Results are obtained on a reduced model, as a proof of concept : the method allows to defined an optimal strategy for a given patient. This method could applied to optimize injections schedules in clinical trials.

Full work available at URL: https://arxiv.org/abs/1801.06227

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zbMATH Keywords

dynamic programmingoptimal controlimmune therapy

Mathematics Subject Classification ID

Medical epidemiology (92C60) Dynamic programming (90C39) Applications of optimal control and differential games (49N90)

Cites Work

• Title not available (Why is that?)
• Optimal control in a model of dendritic cell transfection cancer immunotherapy
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• Mathematical models for immunology: current state of the art and future research directions
• Modeling CD4\(^+\) T cells dynamics in HIV-infected patients receiving repeated cycles of exogenous Interleukin 7

Cited In (2)

• On ``Reflections on the concept of optimality of single decision point treatment regimes
• Evaluating the use of generalized dynamic weighted ordinary least squares for individualized HIV treatment strategies

Uses Software

• Monolix

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