Controlling IL-7 injections in HIV-infected patients

Autor: Rodolphe Thiébaut, Huilong Zhang, Chloé Pasin, Laura Villain, François Dufour
Přispěvatelé: Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Quality control and dynamic reliability (CQFD), Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Bordeaux - Sud-Ouest, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Université de Bordeaux (UB)
Jazyk: angličtina
Rok vydání: 2018
Předmět:
CD4-Positive T-Lymphocytes
0301 basic medicine
Computer science
HIV Infections
Bioinformatics
Quantitative Biology - Quantitative Methods
01 natural sciences
010104 statistics & probability
Hiv infected patients
Mathematics - Optimization and Control
Quantitative Methods (q-bio.QM)
General Environmental Science
Human studies
General Neuroscience
Combined Modality Therapy
Markov Chains
Recombinant Proteins
SISTM
3. Good health
Optimal control
Computational Theory and Mathematics
[SDV.IMM]Life Sciences [q-bio]/Immunology
Immunotherapy
[MATH.MATH-OC]Mathematics [math]/Optimization and Control [math.OC]
General Agricultural and Biological Sciences
Algorithms
Anti-HIV Agents
General Mathematics
Immunology
Dose-Response Relationship
Immunologic
Context (language use)
Markov model
Dynamic programming
Reduced model
Drug Administration Schedule
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
FOS: Mathematics
Antiretroviral treatment
Humans
Computer Simulation
0101 mathematics
Pharmacology
Interleukin-7
Models
Immunological
Mathematical Concepts
CD4 Lymphocyte Count
Clinical trial
030104 developmental biology
Immune therapy
Optimization and Control (math.OC)
FOS: Biological sciences
[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Zdroj: Bulletin of Mathematical Biology
Bulletin of Mathematical Biology, Springer Verlag, 2018, ⟨10.1007/s11538-018-0465-8⟩
Bulletin of Mathematical Biology, 2018, ⟨10.1007/s11538-018-0465-8⟩
Bulletin of Mathematical Biology, Springer Verlag, 2018, 80 (9), pp.2349-2377. ⟨10.1007/s11538-018-0465-8⟩
Bulletin of Mathematical Biology, Springer Verlag, 2018
ISSN: 0092-8240
1522-9602
DOI: 10.1007/s11538-018-0465-8⟩
Popis: Immune interventions consisting in repeated injections are broadly used as they are thought to improve the quantity and the quality of the immune response. However, they also raise several questions that remain unanswered, in particular the number of injections to make or the delay to respect between different injections to achieve 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 interleukin-7 (IL-7) injections in HIV-infected patients under antiretroviral treatment, but still unable to restore normal levels of [Formula: see text] T lymphocytes. Clinical trials have already shown that repeated cycles of injections of IL-7 could help maintaining [Formula: see text] T lymphocytes levels over the limit of 500 cells/[Formula: see text]L, by affecting proliferation and survival of [Formula: see text] T cells. We then aim at answering the question: how to maintain a patients level of [Formula: see text] T lymphocytes by using a minimum number of injections (i.e., optimizing the strategy of injections)? Based on mechanistic models that were previously developed for the dynamics of [Formula: see text] 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 define an optimal strategy for a given patient. This method could be applied to optimize injections schedules in clinical trials.
Databáze: OpenAIRE
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