Impact of Early Versus Late Antiretroviral Treatment Initiation on Naive T Lymphocytes in HIV-1-Infected Children and Adolescents – The-ANRS-EP59-CLEAC Study
BackgroundThe early initiation of antiretroviral therapy (ART) in HIV-1-infected infants reduces mortality and prevents early CD4 T-cell loss. However, the impact of early ART on the immune system has not been thoroughly investigated in children over five years of age or adolescents. Here, we descri...
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.662894/full |
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| author | Pierre Frange Pierre Frange Pierre Frange Thomas Montange Thomas Montange Jérôme Le Chenadec Damien Batalie Damien Batalie Ingrid Fert Ingrid Fert Catherine Dollfus Albert Faye Stéphane Blanche Anne Chacé Corine Fourcade Isabelle Hau Martine Levine Nizar Mahlaoui Valérie Marcou Marie-Dominique Tabone Florence Veber Alexandre Hoctin Thierry Wack Véronique Avettand-Fenoël Véronique Avettand-Fenoël Josiane Warszawski Josiane Warszawski Florence Buseyne Florence Buseyne |
| author_facet | Pierre Frange Pierre Frange Pierre Frange Thomas Montange Thomas Montange Jérôme Le Chenadec Damien Batalie Damien Batalie Ingrid Fert Ingrid Fert Catherine Dollfus Albert Faye Stéphane Blanche Anne Chacé Corine Fourcade Isabelle Hau Martine Levine Nizar Mahlaoui Valérie Marcou Marie-Dominique Tabone Florence Veber Alexandre Hoctin Thierry Wack Véronique Avettand-Fenoël Véronique Avettand-Fenoël Josiane Warszawski Josiane Warszawski Florence Buseyne Florence Buseyne |
| author_sort | Pierre Frange |
| collection | DOAJ |
| description | BackgroundThe early initiation of antiretroviral therapy (ART) in HIV-1-infected infants reduces mortality and prevents early CD4 T-cell loss. However, the impact of early ART on the immune system has not been thoroughly investigated in children over five years of age or adolescents. Here, we describe the levels of naive CD4 and CD8 T lymphocytes (CD4/CD8TN), reflecting the quality of immune reconstitution, as a function of the timing of ART initiation (early (<6 months) versus late (≥24 months of age)).MethodsThe ANRS-EP59-CLEAC study enrolled 27 children (5-12 years of age) and nine adolescents (13-17 years of age) in the early-treatment group, and 19 children (L-Ch) and 21 adolescents (L-Ado) in the late-treatment group. T lymphocytes were analyzed by flow cytometry and plasma markers were analyzed by ELISA. Linear regression analysis was performed with univariate and multivariate models.ResultsAt the time of evaluation, all patients were on ART and had a good immunovirological status: 83% had HIV RNA loads below 50 copies/mL and the median CD4 T-cell count was 856 cells/µL (interquartile range: 685-1236 cells/µL). In children, early ART was associated with higher CD8TN percentages (medians: 48.7% vs. 31.0%, P = 0.001), and a marginally higher CD4TN (61.2% vs. 53.1%, P = 0.33). In adolescents, early ART was associated with low CD4TN percentages and less differentiated memory CD8 T cells. CD4TN and CD8TN levels were inversely related to cellular activation and gut permeability.ConclusionIn children and adolescents, the benefits of early ART for CD8TN were clear after long-term ART. The impact of early ART on CD4TN appears to be modest, because pediatric patients treated late respond to HIV-driven CD4 T-lymphocyte loss by the de novo production of TN cells in the thymus. Our data also suggest that current immune activation and/or gut permeability has a negative impact on TN levels.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT02674867. |
| first_indexed | 2024-12-20T02:35:41Z |
| format | Article |
| id | doaj.art-d9809fbebb3b49b08035fd4ff70cc459 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T02:35:41Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d9809fbebb3b49b08035fd4ff70cc4592022-12-21T19:56:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-04-011210.3389/fimmu.2021.662894662894Impact of Early Versus Late Antiretroviral Treatment Initiation on Naive T Lymphocytes in HIV-1-Infected Children and Adolescents – The-ANRS-EP59-CLEAC StudyPierre Frange0Pierre Frange1Pierre Frange2Thomas Montange3Thomas Montange4Jérôme Le Chenadec5Damien Batalie6Damien Batalie7Ingrid Fert8Ingrid Fert9Catherine Dollfus10Albert Faye11Stéphane Blanche12Anne Chacé13Corine Fourcade14Isabelle Hau15Martine Levine16Nizar Mahlaoui17Valérie Marcou18Marie-Dominique Tabone19Florence Veber20Alexandre Hoctin21Thierry Wack22Véronique Avettand-Fenoël23Véronique Avettand-Fenoël24Josiane Warszawski25Josiane Warszawski26Florence Buseyne27Florence Buseyne28Immunologie, hématologie et rhumatologie pédiatrique, hôpital Necker–Enfants malades, AP–HP- Centre – Université de Paris, Paris, FranceLaboratoire de microbiologie clinique, hôpital Necker–Enfants malades, AP–HP-Centre – Université de Paris, Paris, FranceEHU 7328 PACT, Institut Imagine, Université de Paris, Paris, FranceUnité Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, Paris, FranceDépartement de Virologie, UMR CNRS 3569 Institut Pasteur, Paris, FranceDépartment d’épidémiologie, Centre de Recherche en Épidémiologie et Santé des Populations, INSERM U1018, Le Kremlin-Bicêtre, Villejuif, FranceUnité Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, Paris, FranceDépartement de Virologie, UMR CNRS 3569 Institut Pasteur, Paris, FranceUnité Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, Paris, FranceDépartement de Virologie, UMR CNRS 3569 Institut Pasteur, Paris, FranceHémato-oncologie pédiatrique, Hôpital Trousseau, AP-HP, Paris, FrancePédiatrie Générale, Hôpital Robert Debré, AP-HP, Paris, FranceImmunologie, hématologie et rhumatologie pédiatrique, hôpital Necker–Enfants malades, AP–HP- Centre – Université de Paris, Paris, FrancePédiatrie et néonatologie, Centre hospitalier intercommunal de Villeuneuve-Saint-Georges, Villeuneuve-Saint-Georges, France0Pédiatrie Générale, Hôpital Bicêtre, AP-HP, Paris, France1Pédiatrie Générale, Centre hospitalier intercommunal de Créteil, Créteil, France2Immuno-hématologie pédiatrique, Hôpital Robert Debré, AP-HP, Paris, FranceImmunologie, hématologie et rhumatologie pédiatrique, hôpital Necker–Enfants malades, AP–HP- Centre – Université de Paris, Paris, France3Médecine et réanimation néonatale, Hôpital Cochin, AP-HP-Centre – Université de Paris, Paris, FranceHémato-oncologie pédiatrique, Hôpital Trousseau, AP-HP, Paris, FranceImmunologie, hématologie et rhumatologie pédiatrique, hôpital Necker–Enfants malades, AP–HP- Centre – Université de Paris, Paris, FranceDépartment d’épidémiologie, Centre de Recherche en Épidémiologie et Santé des Populations, INSERM U1018, Le Kremlin-Bicêtre, Villejuif, FranceDépartment d’épidémiologie, Centre de Recherche en Épidémiologie et Santé des Populations, INSERM U1018, Le Kremlin-Bicêtre, Villejuif, FranceLaboratoire de microbiologie clinique, hôpital Necker–Enfants malades, AP–HP-Centre – Université de Paris, Paris, France4CNRS 8104/INSERM U1016, Institut Cochin, Université Paris Descartes, Paris, FranceDépartment d’épidémiologie, Centre de Recherche en Épidémiologie et Santé des Populations, INSERM U1018, Le Kremlin-Bicêtre, Villejuif, France5INED, Université Paris Sud, Le Kremlin-Bicêtre, Orsay, FranceUnité Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, Paris, FranceDépartement de Virologie, UMR CNRS 3569 Institut Pasteur, Paris, FranceBackgroundThe early initiation of antiretroviral therapy (ART) in HIV-1-infected infants reduces mortality and prevents early CD4 T-cell loss. However, the impact of early ART on the immune system has not been thoroughly investigated in children over five years of age or adolescents. Here, we describe the levels of naive CD4 and CD8 T lymphocytes (CD4/CD8TN), reflecting the quality of immune reconstitution, as a function of the timing of ART initiation (early (<6 months) versus late (≥24 months of age)).MethodsThe ANRS-EP59-CLEAC study enrolled 27 children (5-12 years of age) and nine adolescents (13-17 years of age) in the early-treatment group, and 19 children (L-Ch) and 21 adolescents (L-Ado) in the late-treatment group. T lymphocytes were analyzed by flow cytometry and plasma markers were analyzed by ELISA. Linear regression analysis was performed with univariate and multivariate models.ResultsAt the time of evaluation, all patients were on ART and had a good immunovirological status: 83% had HIV RNA loads below 50 copies/mL and the median CD4 T-cell count was 856 cells/µL (interquartile range: 685-1236 cells/µL). In children, early ART was associated with higher CD8TN percentages (medians: 48.7% vs. 31.0%, P = 0.001), and a marginally higher CD4TN (61.2% vs. 53.1%, P = 0.33). In adolescents, early ART was associated with low CD4TN percentages and less differentiated memory CD8 T cells. CD4TN and CD8TN levels were inversely related to cellular activation and gut permeability.ConclusionIn children and adolescents, the benefits of early ART for CD8TN were clear after long-term ART. The impact of early ART on CD4TN appears to be modest, because pediatric patients treated late respond to HIV-driven CD4 T-lymphocyte loss by the de novo production of TN cells in the thymus. Our data also suggest that current immune activation and/or gut permeability has a negative impact on TN levels.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT02674867.https://www.frontiersin.org/articles/10.3389/fimmu.2021.662894/fullHIV-1childrenadolescentsearly ARTT lymphocytenaive T lymphocyte |
| spellingShingle | Pierre Frange Pierre Frange Pierre Frange Thomas Montange Thomas Montange Jérôme Le Chenadec Damien Batalie Damien Batalie Ingrid Fert Ingrid Fert Catherine Dollfus Albert Faye Stéphane Blanche Anne Chacé Corine Fourcade Isabelle Hau Martine Levine Nizar Mahlaoui Valérie Marcou Marie-Dominique Tabone Florence Veber Alexandre Hoctin Thierry Wack Véronique Avettand-Fenoël Véronique Avettand-Fenoël Josiane Warszawski Josiane Warszawski Florence Buseyne Florence Buseyne Impact of Early Versus Late Antiretroviral Treatment Initiation on Naive T Lymphocytes in HIV-1-Infected Children and Adolescents – The-ANRS-EP59-CLEAC Study Frontiers in Immunology HIV-1 children adolescents early ART T lymphocyte naive T lymphocyte |
| title | Impact of Early Versus Late Antiretroviral Treatment Initiation on Naive T Lymphocytes in HIV-1-Infected Children and Adolescents – The-ANRS-EP59-CLEAC Study |
| title_full | Impact of Early Versus Late Antiretroviral Treatment Initiation on Naive T Lymphocytes in HIV-1-Infected Children and Adolescents – The-ANRS-EP59-CLEAC Study |
| title_fullStr | Impact of Early Versus Late Antiretroviral Treatment Initiation on Naive T Lymphocytes in HIV-1-Infected Children and Adolescents – The-ANRS-EP59-CLEAC Study |
| title_full_unstemmed | Impact of Early Versus Late Antiretroviral Treatment Initiation on Naive T Lymphocytes in HIV-1-Infected Children and Adolescents – The-ANRS-EP59-CLEAC Study |
| title_short | Impact of Early Versus Late Antiretroviral Treatment Initiation on Naive T Lymphocytes in HIV-1-Infected Children and Adolescents – The-ANRS-EP59-CLEAC Study |
| title_sort | impact of early versus late antiretroviral treatment initiation on naive t lymphocytes in hiv 1 infected children and adolescents the anrs ep59 cleac study |
| topic | HIV-1 children adolescents early ART T lymphocyte naive T lymphocyte |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.662894/full |
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