<?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-03161958v2</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="2026-05-25T01:30:53+02:00"/>
      </publicationStmt>
      <sourceDesc>
        <p part="N">HAL API Platform</p>
      </sourceDesc>
    </fileDesc>
  </teiHeader>
  <text>
    <body>
      <listBibl>
        <biblFull>
          <titleStmt>
            <title xml:lang="en">Adaptive protocols based on predictions from a mechanistic model of the effect of IL7 on CD4 counts</title>
            <author role="aut">
              <persName>
                <forename type="first">Laura</forename>
                <surname>Villain</surname>
              </persName>
              <email type="md5">c6401e5039224501bfd3e2d1310d0413</email>
              <email type="domain">inria.fr</email>
              <idno type="idhal" notation="numeric">832637</idno>
              <idno type="halauthorid" notation="string">133105-832637</idno>
              <affiliation ref="#struct-219689"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Daniel</forename>
                <surname>Commenges</surname>
              </persName>
              <email type="md5">103005b79db5cad1459d2c3e50e1a69d</email>
              <email type="domain">isped.u-bordeaux2.fr</email>
              <idno type="idhal" notation="numeric">838345</idno>
              <idno type="halauthorid" notation="string">129220-838345</idno>
              <affiliation ref="#struct-55677"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Chloé</forename>
                <surname>Pasin</surname>
              </persName>
              <email type="md5">7cca091bdf4642764664b281eb6e2f62</email>
              <email type="domain">inria.fr</email>
              <idno type="idhal" notation="numeric">1039517</idno>
              <idno type="halauthorid" notation="string">1074563-1039517</idno>
              <affiliation ref="#struct-219689"/>
            </author>
            <author role="aut">
              <persName>
                <forename type="first">Mélanie</forename>
                <surname>Prague</surname>
              </persName>
              <email type="md5">623e9e9cd93474748f5b45f3f33fda76</email>
              <email type="domain">inria.fr</email>
              <idno type="idhal" notation="string">mprague</idno>
              <idno type="idhal" notation="numeric">11146</idno>
              <idno type="halauthorid" notation="string">15545-11146</idno>
              <idno type="ORCID">https://orcid.org/0000-0001-9809-7848</idno>
              <idno type="IDREF">https://www.idref.fr/175063427</idno>
              <affiliation ref="#struct-219689"/>
            </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-259761"/>
              <affiliation ref="#struct-219689"/>
            </author>
            <editor role="depositor">
              <persName>
                <forename>Laura</forename>
                <surname>Villain</surname>
              </persName>
              <email type="md5">e80de253f28aa6111066d75b1bac9e1c</email>
              <email type="domain">gmail.com</email>
            </editor>
          </titleStmt>
          <editionStmt>
            <edition n="v2" type="current">
              <date type="whenSubmitted">2019-01-08 10:55:48</date>
              <date type="whenModified">2025-03-17 19:47:49</date>
              <date type="whenReleased">2019-01-08 11:31:53</date>
              <date type="whenProduced">2018-09-26</date>
              <date type="whenEndEmbargoed">2019-01-08</date>
              <ref type="file" target="https://inria.hal.science/hal-03161958v2/document">
                <date notBefore="2019-01-08"/>
              </ref>
              <ref type="file" subtype="author" n="1" target="https://inria.hal.science/hal-03161958v2/file/adaptive-protocols.pdf" id="file-1973045-1995996">
                <date notBefore="2019-01-08"/>
              </ref>
              <ref type="externalLink" target="https://hal.inria.fr/hal-01973045/file/adaptive-protocols.pdf"/>
            </edition>
            <edition n="v1">
              <date type="whenSubmitted">2021-03-08 10:59:43</date>
            </edition>
            <respStmt>
              <resp>contributor</resp>
              <name key="580714">
                <persName>
                  <forename>Laura</forename>
                  <surname>Villain</surname>
                </persName>
                <email type="md5">e80de253f28aa6111066d75b1bac9e1c</email>
                <email type="domain">gmail.com</email>
              </name>
            </respStmt>
          </editionStmt>
          <publicationStmt>
            <distributor>CCSD</distributor>
            <idno type="halId">hal-03161958</idno>
            <idno type="halUri">https://inria.hal.science/hal-03161958</idno>
            <idno type="halBibtex">villain:hal-03161958</idno>
            <idno type="halRefHtml">&lt;i&gt;Statistics in Medicine&lt;/i&gt;, 2018, 38 (2), pp.221-235. &lt;a target="_blank" href="https://dx.doi.org/10.1002/sim.7957"&gt;&amp;#x27E8;10.1002/sim.7957&amp;#x27E9;&lt;/a&gt;</idno>
            <idno type="halRef">Statistics in Medicine, 2018, 38 (2), pp.221-235. &amp;#x27E8;10.1002/sim.7957&amp;#x27E9;</idno>
            <availability status="restricted">
              <licence target="https://about.hal.science/hal-authorisation-v1/">HAL Authorization<ref corresp="#file-1973045-1995996"/></licence>
            </availability>
          </publicationStmt>
          <seriesStmt>
            <idno type="stamp" n="INRIA">INRIA - Institut National de Recherche en Informatique et en Automatique</idno>
            <idno type="stamp" n="INRIA-BORDEAUX">INRIA Bordeaux - Sud-Ouest</idno>
            <idno type="stamp" n="INRIA_TEST">INRIA - Institut National de Recherche en Informatique et en Automatique</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="U1219" corresp="INSERM">Bordeaux Population Health</idno>
            <idno type="stamp" n="INRIAARTDOI">INRIAARTDOI</idno>
            <idno type="stamp" n="UNIVERSITE-BORDEAUX">Université de Bordeaux</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">Adaptive protocols based on predictions from a mechanistic model of the effect of IL7 on CD4 counts</title>
                <author role="aut">
                  <persName>
                    <forename type="first">Laura</forename>
                    <surname>Villain</surname>
                  </persName>
                  <email type="md5">c6401e5039224501bfd3e2d1310d0413</email>
                  <email type="domain">inria.fr</email>
                  <idno type="idhal" notation="numeric">832637</idno>
                  <idno type="halauthorid" notation="string">133105-832637</idno>
                  <affiliation ref="#struct-219689"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Daniel</forename>
                    <surname>Commenges</surname>
                  </persName>
                  <email type="md5">103005b79db5cad1459d2c3e50e1a69d</email>
                  <email type="domain">isped.u-bordeaux2.fr</email>
                  <idno type="idhal" notation="numeric">838345</idno>
                  <idno type="halauthorid" notation="string">129220-838345</idno>
                  <affiliation ref="#struct-55677"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Chloé</forename>
                    <surname>Pasin</surname>
                  </persName>
                  <email type="md5">7cca091bdf4642764664b281eb6e2f62</email>
                  <email type="domain">inria.fr</email>
                  <idno type="idhal" notation="numeric">1039517</idno>
                  <idno type="halauthorid" notation="string">1074563-1039517</idno>
                  <affiliation ref="#struct-219689"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Mélanie</forename>
                    <surname>Prague</surname>
                  </persName>
                  <email type="md5">623e9e9cd93474748f5b45f3f33fda76</email>
                  <email type="domain">inria.fr</email>
                  <idno type="idhal" notation="string">mprague</idno>
                  <idno type="idhal" notation="numeric">11146</idno>
                  <idno type="halauthorid" notation="string">15545-11146</idno>
                  <idno type="ORCID">https://orcid.org/0000-0001-9809-7848</idno>
                  <idno type="IDREF">https://www.idref.fr/175063427</idno>
                  <affiliation ref="#struct-219689"/>
                </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-259761"/>
                  <affiliation ref="#struct-219689"/>
                </author>
              </analytic>
              <monogr>
                <idno type="halJournalId" status="VALID">19150</idno>
                <idno type="issn">0277-6715</idno>
                <idno type="eissn">1097-0258</idno>
                <title level="j">Statistics in Medicine</title>
                <imprint>
                  <publisher>Wiley-Blackwell</publisher>
                  <biblScope unit="volume">38</biblScope>
                  <biblScope unit="issue">2</biblScope>
                  <biblScope unit="pp">221-235</biblScope>
                  <date type="datePub">2018-09-26</date>
                </imprint>
              </monogr>
              <idno type="doi">10.1002/sim.7957</idno>
            </biblStruct>
          </sourceDesc>
          <profileDesc>
            <langUsage>
              <language ident="en">English</language>
            </langUsage>
            <textClass>
              <keywords scheme="author">
                <term xml:lang="en">Adaptive protocols</term>
                <term xml:lang="en">HIV</term>
                <term xml:lang="en">Interleukine 7</term>
                <term xml:lang="en">Mechanistic models</term>
              </keywords>
              <classCode scheme="halDomain" n="stat.ap">Statistics [stat]/Applications [stat.AP]</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>In human immunodeficiency virus-infected patients, antiretroviral therapy suppresses the viral replication, which is followed in most patients by a restoration of CD4+ T cells pool. For patients who fail to do so, repeated injections of exogenous interleukin 7 (IL7) are experimented. The IL7 is a cytokine that is involved in the T cell homeostasis and the INSPIRE study has shown that injections of IL7 induced a proliferation of CD4+ T cells. Phase I/II INSPIRE 2 and 3 studies have evaluated a protocol in which a first cycle of three IL7 injections is followed by a new cycle at each visit when the patient has less than 550 CD4 cells/í µí¼L. Restoration of the CD4 concentration has been demonstrated, but the long-term best adaptive protocol is yet to be determined. A mechanistic model of the evolution of CD4 after IL7 injections has been developed, which is based on a system of ordinary differential equations and includes random effects. Based on the estimation of this model, we use a Bayesian approach to forecast the dynamics of CD4 in new patients. We propose four prediction-based adaptive protocols of injections to minimize the time spent under 500 CD4 cells/í µí¼L for each patient, without increasing the number of injections received too much. We show that our protocols significantly reduce the time spent under 500 CD4 over a period of two years, without increasing the number of injections. These protocols have the potential to increase the efficiency of this therapy.</p>
            </abstract>
          </profileDesc>
        </biblFull>
      </listBibl>
    </body>
    <back>
      <listOrg type="structures">
        <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="laboratory" xml:id="struct-55677" status="OLD">
          <orgName>Epidémiologie et Biostatistique [Bordeaux]</orgName>
          <desc>
            <address>
              <addrLine>146, rue Léo-Saignat 33076 Bordeaux</addrLine>
              <country key="FR"/>
            </address>
          </desc>
          <listRelation>
            <relation active="#struct-91134" type="direct"/>
            <relation name="U897" 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="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-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="institution" xml:id="struct-91134" status="OLD">
          <orgName>Université Bordeaux Segalen - Bordeaux 2</orgName>
          <desc>
            <address>
              <addrLine>146 rue Léo Saignat - 33076 Bordeaux cedex</addrLine>
              <country key="FR"/>
            </address>
            <ref type="url">http://www.univ-bordeauxsegalen.fr/</ref>
          </desc>
        </org>
      </listOrg>
    </back>
  </text>
</TEI>