<?xml version="1.0" encoding="utf-8"?>
<TEI xmlns="http://www.tei-c.org/ns/1.0" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:hal="http://hal.archives-ouvertes.fr/" xmlns:gml="http://www.opengis.net/gml/3.3/" xmlns:gmlce="http://www.opengis.net/gml/3.3/ce" version="1.1" xsi:schemaLocation="http://www.tei-c.org/ns/1.0 http://api.archives-ouvertes.fr/documents/aofr-sword.xsd">
  <teiHeader>
    <fileDesc>
      <titleStmt>
        <title>HAL TEI export of hal-03063888v2</title>
      </titleStmt>
      <publicationStmt>
        <distributor>CCSD</distributor>
        <availability status="restricted">
          <licence target="https://creativecommons.org/publicdomain/zero/1.0/">CC0 1.0 - Universal</licence>
        </availability>
        <date when="2026-05-17T18:20:02+02:00"/>
      </publicationStmt>
      <sourceDesc>
        <p part="N">HAL API Platform</p>
      </sourceDesc>
    </fileDesc>
  </teiHeader>
  <text>
    <body>
      <listBibl>
        <biblFull>
          <titleStmt>
            <title xml:lang="en">Controlling IL-7 injections in HIV-infected patients</title>
            <author role="aut">
              <persName>
                <forename type="first">Chloé</forename>
                <surname>Pasin</surname>
              </persName>
              <idno type="halauthorid">1074563-0</idno>
              <affiliation ref="#struct-220073"/>
              <affiliation ref="#struct-219689"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">François</forename>
                <surname>Dufour</surname>
              </persName>
              <email type="md5">41b313e5d0ffec098d0bd58cbd4c43de</email>
              <email type="domain">math.u-bordeaux.fr</email>
              <idno type="idhal" notation="string">francois-dufour</idno>
              <idno type="idhal" notation="numeric">12044</idno>
              <idno type="halauthorid" notation="string">33506-12044</idno>
              <idno type="ORCID">https://orcid.org/0000-0001-6653-2024</idno>
              <idno type="IDREF">https://www.idref.fr/127261680</idno>
              <affiliation ref="#struct-55994"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Laura</forename>
                <surname>Villain</surname>
              </persName>
              <idno type="halauthorid">133105-0</idno>
              <affiliation ref="#struct-219689"/>
              <affiliation ref="#struct-220073"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Huilong</forename>
                <surname>Zhang</surname>
              </persName>
              <email type="md5">21bdb6de9618c8cfa669cc718e734867</email>
              <email type="domain">math.u-bordeaux1.fr</email>
              <idno type="idhal" notation="numeric">855584</idno>
              <idno type="halauthorid" notation="string">145043-855584</idno>
              <affiliation ref="#struct-55994"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Rodolphe</forename>
                <surname>Thiébaut</surname>
              </persName>
              <email type="md5">242f217052cdd1b15e9288ab507c175b</email>
              <email type="domain">u-bordeaux.fr</email>
              <idno type="idhal" notation="string">rodolphe-thiebaut</idno>
              <idno type="idhal" notation="numeric">175125</idno>
              <idno type="halauthorid" notation="string">32082-175125</idno>
              <idno type="ORCID">https://orcid.org/0000-0002-5235-3962</idno>
              <idno type="IDREF">https://www.idref.fr/071580735</idno>
              <affiliation ref="#struct-220073"/>
              <affiliation ref="#struct-219689"/>
            </author>
            <editor role="depositor">
              <persName>
                <forename>Chloé</forename>
                <surname>Pasin</surname>
              </persName>
              <email type="md5">fb771b70045cd47ea5639a78a6cb1663</email>
              <email type="domain">u-bordeaux.fr</email>
            </editor>
            <funder ref="#projanr-37855"/>
          </titleStmt>
          <editionStmt>
            <edition n="v2" type="current">
              <date type="whenSubmitted">2018-11-23 15:34:56</date>
              <date type="whenModified">2025-04-10 10:23:56</date>
              <date type="whenReleased">2018-11-23 18:47:22</date>
              <date type="whenProduced">2018-08-02</date>
              <date type="whenEndEmbargoed">2018-11-23</date>
              <ref type="file" target="https://inria.hal.science/hal-03063888v2/document">
                <date notBefore="2018-11-23"/>
              </ref>
              <ref type="file" subtype="author" n="1" target="https://inria.hal.science/hal-03063888v2/file/main.pdf" id="file-1933170-1962171">
                <date notBefore="2018-11-23"/>
              </ref>
              <ref type="externalLink" target="http://arxiv.org/pdf/1801.06227"/>
            </edition>
            <edition n="v1">
              <date type="whenSubmitted">2020-12-14 11:59:01</date>
            </edition>
            <respStmt>
              <resp>contributor</resp>
              <name key="663519">
                <persName>
                  <forename>Chloé</forename>
                  <surname>Pasin</surname>
                </persName>
                <email type="md5">fb771b70045cd47ea5639a78a6cb1663</email>
                <email type="domain">u-bordeaux.fr</email>
              </name>
            </respStmt>
          </editionStmt>
          <publicationStmt>
            <distributor>CCSD</distributor>
            <idno type="halId">hal-03063888</idno>
            <idno type="halUri">https://inria.hal.science/hal-03063888</idno>
            <idno type="halBibtex">pasin:hal-03063888</idno>
            <idno type="halRefHtml">&lt;i&gt;Bulletin of Mathematical Biology&lt;/i&gt;, 2018, &lt;a target="_blank" href="https://dx.doi.org/10.1007/s11538-018-0465-8"&gt;&amp;#x27E8;10.1007/s11538-018-0465-8&amp;#x27E9;&lt;/a&gt;</idno>
            <idno type="halRef">Bulletin of Mathematical Biology, 2018, &amp;#x27E8;10.1007/s11538-018-0465-8&amp;#x27E9;</idno>
            <availability status="restricted">
              <licence target="https://about.hal.science/hal-authorisation-v1/">HAL Authorization<ref corresp="#file-1933170-1962171"/></licence>
            </availability>
          </publicationStmt>
          <seriesStmt>
            <idno type="stamp" n="CNRS">CNRS - Centre national de la recherche scientifique</idno>
            <idno type="stamp" n="INRIA">INRIA - Institut National de Recherche en Informatique et en Automatique</idno>
            <idno type="stamp" n="IMB">Institut de Mathématiques de Bordeaux</idno>
            <idno type="stamp" n="INRIA-BORDEAUX">INRIA Bordeaux - Sud-Ouest</idno>
            <idno type="stamp" n="INSMI">CNRS-INSMI - INstitut des Sciences Mathématiques et de leurs Interactions</idno>
            <idno type="stamp" n="INRIA_TEST">INRIA - Institut National de Recherche en Informatique et en Automatique</idno>
            <idno type="stamp" n="UPEC" corresp="CV_UPEC">Université Paris-Est Créteil Val-de-Marne</idno>
            <idno type="stamp" n="TESTALAIN1">TESTALAIN1</idno>
            <idno type="stamp" n="TESTBORDEAUX">TESTBORDEAUX</idno>
            <idno type="stamp" n="INRIA2">INRIA 2</idno>
            <idno type="stamp" n="TDS-MACS">Réseau de recherche en Théorie des Systèmes Distribués, Modélisation, Analyse et Contrôle des Systèmes</idno>
            <idno type="stamp" n="TEST-HALCNRS">Collection test HAL CNRS</idno>
            <idno type="stamp" n="ANR">ANR</idno>
            <idno type="stamp" n="U1219" corresp="INSERM">Bordeaux Population Health</idno>
            <idno type="stamp" n="INRIAARTDOI">INRIAARTDOI</idno>
            <idno type="stamp" n="UNIVERSITE-BORDEAUX">Université de Bordeaux</idno>
            <idno type="stamp" n="TEST-UPEC-ODD" corresp="UPEC">TEST UPEC ODD</idno>
          </seriesStmt>
          <notesStmt>
            <note type="audience" n="2">International</note>
            <note type="popular" n="0">No</note>
            <note type="peer" n="1">Yes</note>
          </notesStmt>
          <sourceDesc>
            <biblStruct>
              <analytic>
                <title xml:lang="en">Controlling IL-7 injections in HIV-infected patients</title>
                <author role="aut">
                  <persName>
                    <forename type="first">Chloé</forename>
                    <surname>Pasin</surname>
                  </persName>
                  <idno type="halauthorid">1074563-0</idno>
                  <affiliation ref="#struct-220073"/>
                  <affiliation ref="#struct-219689"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">François</forename>
                    <surname>Dufour</surname>
                  </persName>
                  <email type="md5">41b313e5d0ffec098d0bd58cbd4c43de</email>
                  <email type="domain">math.u-bordeaux.fr</email>
                  <idno type="idhal" notation="string">francois-dufour</idno>
                  <idno type="idhal" notation="numeric">12044</idno>
                  <idno type="halauthorid" notation="string">33506-12044</idno>
                  <idno type="ORCID">https://orcid.org/0000-0001-6653-2024</idno>
                  <idno type="IDREF">https://www.idref.fr/127261680</idno>
                  <affiliation ref="#struct-55994"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Laura</forename>
                    <surname>Villain</surname>
                  </persName>
                  <idno type="halauthorid">133105-0</idno>
                  <affiliation ref="#struct-219689"/>
                  <affiliation ref="#struct-220073"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Huilong</forename>
                    <surname>Zhang</surname>
                  </persName>
                  <email type="md5">21bdb6de9618c8cfa669cc718e734867</email>
                  <email type="domain">math.u-bordeaux1.fr</email>
                  <idno type="idhal" notation="numeric">855584</idno>
                  <idno type="halauthorid" notation="string">145043-855584</idno>
                  <affiliation ref="#struct-55994"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Rodolphe</forename>
                    <surname>Thiébaut</surname>
                  </persName>
                  <email type="md5">242f217052cdd1b15e9288ab507c175b</email>
                  <email type="domain">u-bordeaux.fr</email>
                  <idno type="idhal" notation="string">rodolphe-thiebaut</idno>
                  <idno type="idhal" notation="numeric">175125</idno>
                  <idno type="halauthorid" notation="string">32082-175125</idno>
                  <idno type="ORCID">https://orcid.org/0000-0002-5235-3962</idno>
                  <idno type="IDREF">https://www.idref.fr/071580735</idno>
                  <affiliation ref="#struct-220073"/>
                  <affiliation ref="#struct-219689"/>
                </author>
              </analytic>
              <monogr>
                <idno type="halJournalId" status="VALID">11380</idno>
                <idno type="issn">0092-8240</idno>
                <idno type="eissn">1522-9602</idno>
                <title level="j">Bulletin of Mathematical Biology</title>
                <imprint>
                  <publisher>Springer Verlag</publisher>
                  <date type="datePub">2018-08-02</date>
                </imprint>
              </monogr>
              <idno type="doi">10.1007/s11538-018-0465-8</idno>
            </biblStruct>
          </sourceDesc>
          <profileDesc>
            <langUsage>
              <language ident="en">English</language>
            </langUsage>
            <textClass>
              <keywords scheme="author">
                <term xml:lang="en">Dynamic programming</term>
                <term xml:lang="en">Immune therapy</term>
                <term xml:lang="en">Optimal control</term>
              </keywords>
              <classCode scheme="halDomain" n="math.math-oc">Mathematics [math]/Optimization and Control [math.OC]</classCode>
              <classCode scheme="halDomain" n="sdv.imm">Life Sciences [q-bio]/Immunology</classCode>
              <classCode scheme="halTypology" n="ART">Journal articles</classCode>
              <classCode scheme="halOldTypology" n="ART">Journal articles</classCode>
              <classCode scheme="halTreeTypology" n="ART">Journal articles</classCode>
            </textClass>
            <abstract xml:lang="en">
              <p>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 unan-swered, 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 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/µL, by affecting proliferation and survival of CD4 + T cells. We then aim at answering the question : how to maintain a patients level of CD4 + 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 CD4+ T lymphocytes in this context, we model the process by a piecewise deter-ministic Markov model. We then address the question by using some recently 2 Chloé Pasin et al. 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.</p>
            </abstract>
          </profileDesc>
        </biblFull>
      </listBibl>
    </body>
    <back>
      <listOrg type="structures">
        <org type="laboratory" xml:id="struct-220073" status="VALID">
          <orgName>Vaccine Research Institute [Créteil, France]</orgName>
          <orgName type="acronym">VRI</orgName>
          <desc>
            <address>
              <addrLine>61 avenue du Général de Gaulle 94010 Créteil Cedex France</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.recherche-vaccinvih.fr/</ref>
          </desc>
          <listRelation>
            <relation active="#struct-420786" type="direct"/>
          </listRelation>
        </org>
        <org type="researchteam" xml:id="struct-219689" status="VALID">
          <idno type="RNSR">201321095C</idno>
          <idno type="ROR">https://ror.org/026t7px13</idno>
          <orgName>Statistics In System biology and Translational Medicine</orgName>
          <orgName type="acronym">SISTM</orgName>
          <date type="start">2016-01-01</date>
          <date type="end">2027-12-31</date>
          <desc>
            <address>
              <addrLine>200, avenue de la Vieille Tour 33405 Talence cedex 146 Rue Léo Saignat33076 Bordeaux cedex</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.inria.fr/equipes/sistm</ref>
          </desc>
          <listRelation>
            <relation active="#struct-104751" type="direct"/>
            <relation active="#struct-300009" type="indirect"/>
            <relation active="#struct-476572" type="direct"/>
            <relation active="#struct-259761" type="indirect"/>
            <relation active="#struct-302259" type="indirect"/>
            <relation name="U1219" active="#struct-303623" type="indirect"/>
          </listRelation>
        </org>
        <org type="researchteam" xml:id="struct-55994" status="OLD">
          <idno type="RNSR">200718997Y</idno>
          <orgName>Quality control and dynamic reliability</orgName>
          <orgName type="acronym">CQFD</orgName>
          <date type="start">2009-01-01</date>
          <date type="end">2020-12-31</date>
          <desc>
            <address>
              <addrLine>200, avenue de la Vieille Tour 33405 Talence cedex</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.inria.fr/equipes/cqfd</ref>
          </desc>
          <listRelation>
            <relation active="#struct-27730" type="direct"/>
            <relation active="#struct-259761" type="indirect"/>
            <relation active="#struct-409745" type="indirect"/>
            <relation name="UMR5251" active="#struct-441569" type="indirect"/>
            <relation active="#struct-104751" type="direct"/>
            <relation active="#struct-300009" type="indirect"/>
          </listRelation>
        </org>
        <org type="institution" xml:id="struct-420786" status="VALID">
          <idno type="IdRef">028021037</idno>
          <idno type="ISNI">0000000121497878</idno>
          <idno type="ROR">https://ror.org/05ggc9x40</idno>
          <orgName>Université Paris-Est Créteil Val-de-Marne - Paris 12</orgName>
          <orgName type="acronym">UPEC UP12</orgName>
          <date type="start">1970-01-01</date>
          <desc>
            <address>
              <addrLine>61 avenue du Général de Gaulle - 94010 Créteil cedex</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.u-pec.fr/</ref>
          </desc>
        </org>
        <org type="laboratory" xml:id="struct-104751" status="VALID">
          <idno type="RNSR">200818243Z</idno>
          <idno type="ROR">https://ror.org/03tjcj052</idno>
          <orgName>Centre Inria de l'Université de Bordeaux</orgName>
          <desc>
            <address>
              <addrLine>200, avenue de la Vieille Tour, 33405 Talence</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.inria.fr/bordeaux/</ref>
          </desc>
          <listRelation>
            <relation active="#struct-300009" type="direct"/>
          </listRelation>
        </org>
        <org type="institution" xml:id="struct-300009" status="VALID">
          <idno type="ROR">https://ror.org/02kvxyf05</idno>
          <orgName>Institut National de Recherche en Informatique et en Automatique</orgName>
          <orgName type="acronym">Inria</orgName>
          <desc>
            <address>
              <addrLine>Domaine de VoluceauRocquencourt - BP 10578153 Le Chesnay Cedex</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.inria.fr/en/</ref>
          </desc>
        </org>
        <org type="laboratory" xml:id="struct-476572" status="VALID">
          <idno type="IdRef">197398162</idno>
          <idno type="RNSR">201622170H</idno>
          <idno type="ROR">https://ror.org/00xzzba89</idno>
          <orgName>Bordeaux population health</orgName>
          <orgName type="acronym">BPH</orgName>
          <desc>
            <address>
              <addrLine>Université de Bordeaux - Case 11 - 146 rue Léo Saignat  33076 Bordeaux cedex</addrLine>
              <country key="FR"/>
            </address>
          </desc>
          <listRelation>
            <relation active="#struct-259761" type="direct"/>
            <relation active="#struct-302259" type="direct"/>
            <relation name="U1219" active="#struct-303623" type="direct"/>
          </listRelation>
        </org>
        <org type="institution" xml:id="struct-259761" status="VALID">
          <idno type="IdRef">175206562</idno>
          <idno type="ROR">https://ror.org/057qpr032</idno>
          <orgName>Université de Bordeaux</orgName>
          <orgName type="acronym">UB</orgName>
          <desc>
            <address>
              <addrLine>35, place Pey Berland - 33076 Bordeaux</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.u-bordeaux.fr/</ref>
          </desc>
        </org>
        <org type="institution" xml:id="struct-302259" status="VALID">
          <orgName>Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)</orgName>
          <desc>
            <address>
              <country key="FR"/>
            </address>
          </desc>
        </org>
        <org type="institution" xml:id="struct-303623" status="VALID">
          <idno type="IdRef">026388278</idno>
          <idno type="ROR">https://ror.org/02vjkv261</idno>
          <orgName>Institut National de la Santé et de la Recherche Médicale</orgName>
          <orgName type="acronym">INSERM</orgName>
          <desc>
            <address>
              <addrLine>101, rue de Tolbiac, 75013 Paris</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.inserm.fr</ref>
          </desc>
        </org>
        <org type="laboratory" xml:id="struct-27730" status="VALID">
          <idno type="IdRef">155051342</idno>
          <idno type="ISNI">0000000123024783</idno>
          <idno type="RNSR">200711916B</idno>
          <idno type="ROR">https://ror.org/05m3r1b84</idno>
          <orgName>Institut de Mathématiques de Bordeaux</orgName>
          <orgName type="acronym">IMB</orgName>
          <date type="start">2003-01-01</date>
          <desc>
            <address>
              <addrLine>351 cours de la Libération 33405 TALENCE CEDEX</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.math.u-bordeaux.fr/IMB/</ref>
          </desc>
          <listRelation>
            <relation active="#struct-259761" type="direct"/>
            <relation active="#struct-409745" type="direct"/>
            <relation name="UMR5251" active="#struct-441569" type="direct"/>
          </listRelation>
        </org>
        <org type="institution" xml:id="struct-409745" status="VALID">
          <orgName>Institut Polytechnique de Bordeaux</orgName>
          <orgName type="acronym">Bordeaux INP</orgName>
          <desc>
            <address>
              <addrLine>Avenue des facultés33405 Talence</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">https://www.bordeaux-inp.fr/fr</ref>
          </desc>
        </org>
        <org type="regroupinstitution" xml:id="struct-441569" status="VALID">
          <idno type="IdRef">02636817X</idno>
          <idno type="ISNI">0000000122597504</idno>
          <idno type="ROR">https://ror.org/02feahw73</idno>
          <orgName>Centre National de la Recherche Scientifique</orgName>
          <orgName type="acronym">CNRS</orgName>
          <date type="start">1939-10-19</date>
          <desc>
            <address>
              <country key="FR"/>
            </address>
            <ref type="url">https://www.cnrs.fr/</ref>
          </desc>
        </org>
      </listOrg>
      <listOrg type="projects">
        <org type="anrProject" xml:id="projanr-37855" status="VALID">
          <idno type="anr">ANR-10-LABX-0077</idno>
          <idno type="program">Laboratoires d'excellence</idno>
          <orgName>VRI</orgName>
          <desc>Initiative for the creation of a Vaccine Research Institute</desc>
          <date type="start">2010</date>
        </org>
      </listOrg>
    </back>
  </text>
</TEI>