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                <surname>Amokrane</surname>
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                <forename type="first">Florence</forename>
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                <forename type="first">Josiane</forename>
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                <forename type="first">Pierre</forename>
                <surname>Frange</surname>
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                <forename>Florence</forename>
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            <funder>The ANRS CLEAC study was supported by the ANRS (French National Agency for Research on AIDS and Viral Hepatitis).</funder>
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            <idno type="stamp" n="UVSQ">Université de Versailles Saint-Quentin-en-Yvelines</idno>
            <idno type="stamp" n="UNIV-PARIS-SACLAY">Université Paris-Saclay</idno>
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                <title xml:lang="en">Initiating antiretroviral treatment early in infancy has long-term benefits on the HIV reservoir in late childhood and adolescence</title>
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                  <persName>
                    <forename type="first">Véronique</forename>
                    <surname>Avettand-Fenoel</surname>
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                    <forename type="first">Adeline</forename>
                    <surname>Melard</surname>
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                  <idno type="halauthorid">1637946-0</idno>
                  <affiliation ref="#struct-1004701"/>
                  <affiliation ref="#struct-557826"/>
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                    <forename type="first">Assia</forename>
                    <surname>Samri</surname>
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                  <persName>
                    <forename type="first">Catherine</forename>
                    <surname>Dollfus</surname>
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                  <idno type="halauthorid">254262-0</idno>
                  <affiliation ref="#struct-360410"/>
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                    <forename type="first">Stéphane</forename>
                    <surname>Blanche</surname>
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                  <idno type="halauthorid">117446-0</idno>
                  <affiliation ref="#struct-557826"/>
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                    <forename type="first">Albert</forename>
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                    <forename type="first">Kahina</forename>
                    <surname>Amokrane</surname>
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                  <persName>
                    <forename type="first">Brigitte</forename>
                    <surname>Autran</surname>
                  </persName>
                  <idno type="halauthorid">224141-0</idno>
                  <affiliation ref="#struct-542033"/>
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                <author role="aut">
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                    <forename type="first">Florence</forename>
                    <surname>Buseyne</surname>
                  </persName>
                  <email type="md5">5ca8b91ab9998ec670f23f4e727dab3b</email>
                  <email type="domain">pasteur.fr</email>
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                <author role="aut">
                  <persName>
                    <forename type="first">Josiane</forename>
                    <surname>Warszawski</surname>
                  </persName>
                  <idno type="halauthorid">254259-0</idno>
                  <affiliation ref="#struct-1004701"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Pierre</forename>
                    <surname>Frange</surname>
                  </persName>
                  <idno type="halauthorid">963890-0</idno>
                  <affiliation ref="#struct-557826"/>
                  <affiliation ref="#struct-487749"/>
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                <author role="aut">
                  <persName>
                    <forename type="first">Anrs-Ep59-Cleac</forename>
                    <surname>Study</surname>
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                  <idno type="halauthorid">2230281-0</idno>
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                <idno type="issn">1058-4838</idno>
                <idno type="eissn">1537-6591</idno>
                <title level="j">Clinical Infectious Diseases</title>
                <imprint>
                  <publisher>Oxford University Press (OUP)</publisher>
                  <date type="datePub">2021-01-04</date>
                </imprint>
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              <idno type="doi">10.1093/cid/ciaa1931</idno>
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              <keywords scheme="author">
                <term xml:lang="en">protective HLA</term>
                <term xml:lang="en">early ART</term>
                <term xml:lang="en">HIV DNA</term>
                <term xml:lang="en">adolescents</term>
                <term xml:lang="en">children</term>
              </keywords>
              <classCode scheme="halDomain" n="sdv.imm.ia">Life Sciences [q-bio]/Immunology/Adaptive immunology</classCode>
              <classCode scheme="halDomain" n="sdv.mp.vir">Life Sciences [q-bio]/Microbiology and Parasitology/Virology</classCode>
              <classCode scheme="halDomain" n="sdv.mhep.me">Life Sciences [q-bio]/Human health and pathology/Emerging diseases</classCode>
              <classCode scheme="halDomain" n="sdv.mhep.mi">Life Sciences [q-bio]/Human health and pathology/Infectious diseases</classCode>
              <classCode scheme="halDomain" n="sdv.mhep.ped">Life Sciences [q-bio]/Human health and pathology/Pediatrics</classCode>
              <classCode scheme="halTypology" n="ART">Journal articles</classCode>
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              <classCode scheme="halTreeTypology" n="ART">Journal articles</classCode>
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            <abstract xml:lang="en">
              <p>BackgroundEarly combined antiretroviral therapy (cART) limits the total HIV-DNA load in children. However, data on its impact in older children and adolescents remain scarce. This study aims to compare HIV reservoirs in children (5-12 years) and adolescents (13-17 years) who started cART before 6 months (early (E-)group) or after 2 years old (late (L-)group). MethodsThe ANRS-EP59-CLEAC study prospectively enrolled 76 HIV-1 perinatally-infected patients who reached HIV-RNA&amp;lt;400 copies/mL less than 24 months after cART initiation, regardless of subsequent viral suppression (E-group: 27 children, 9 adolescents; L-group: 19 children, 21 adolescents). Total and integrated HIV-DNA were quantified in blood and in CD4+ T cell subsets. A substudy assessed HIV reservoir inducibility after ex vivo peripheral blood mononuclear cells (PBMCs) stimulation.ResultsTotal HIV-DNA levels were lower in early- than late-treated patients (Children: 2.14 vs 2.87 log cp/million PBMCs, p&amp;lt;0.0001; Adolescents: 2.25 vs 2.74log, p&amp;lt;0.0001). Low reservoir was independently associated with treatment precocity, protective HLA and low cumulative viremia since cART initiation. The 60 participants with undetectable integrated HIV-DNA started cART earlier than the other patients (4 vs 54 months, p=0.03). In those with sustained virological control, transitional memory and effector memory CD4+T cells were less infected in the E-group than in the L-group (p=0.03 and 0.02, respectively). Viral inducibility of reservoir cells after normalization to HIV-DNA levels was similar between the groups.ConclusionsEarly cART results in a smaller blood HIV reservoir until adolescence, but all tested participants had an inducible reservoir. This deserves cautious consideration for HIV remission strategies.</p>
            </abstract>
            <particDesc>
              <org type="consortium">The ANRS CLEAC study group: Hôpital Armand Trousseau, Paris: Mary-France Courcoux, Catherine Dollfus, Marie-Dominique Tabone, Geneviève Vaudre; Hôpital Bicêtre, Le Kremlin-Bicêtre: Corinne Fourcade, Josiane Warsazawski, Jérôme Lechenadec, Olivia Dialla, Laura Nailler, Lamya Ait Si Selmi, Isabelle Leymarie, Thierry Wack, Alexandre Hoctin, Razika Feraon-Nanache; Centre hospitalier intercommunal de Créteil: Isabelle Hau; Hôpital Delafontaine, Saint-Denis: Cécile Gakobwa; Hôpital Necker-Enfants Malades, Paris: Véronique Avettand-Fenoël, Stéphane Blanche, Marine Fillion, Pierre Frange, Nizar Mahlaoui, Adeline Mélard,Florence Veber, Marie-Christine Mourey; Maternité Port-Royal, Paris: Valérie Marcou; Hôpital Robert Debré, Paris: Albert Faye, Martine Lévine, Sandrine Richard; Pitié-Salpêtrière, Paris: Brigitte Autran, Assia Samri, Mariama Diallo;  Hôpital Saint-Louis: Sophie Caillat-Zucman, Kahina Amokrane, Rayna Ivanova-Derin,  Centre hospitalier intercommunal de Villeneuve-Saint-Georges: Anne Chacé; Institut Pasteur Paris: Florence Buseyne, Thomas Montange, Damien Batalie, Ingrid Fert, Asier Saez-Cirion, Valérie Monceaux, Daniel Scott-Algara; ANRS: Lucie Marchand, Delphine Lebrasseur, Axel Levier.</org>
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