HIV immunological non-responders are characterized by extensive immunosenescence and impaired lymphocyte cytokine production capacity
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Le résumé fourni par la source
Introduction Immunological non-responders (INR) are people living with HIV (PLHIV) who fail to fully restore CD4+ T-cell counts despite complete viral suppression with antiretroviral therapy (ART). INR are at higher risk for non-HIV related morbidity and mortality. Previous research suggest persistent qualitative defects. Methods The 2000HIV study (clinical trials NTC03994835) enrolled 1895 PLHIV, divided in a discovery and validation cohort. PLHIV with CD4 T-cell count <350 cells/mm 3 after ≥2 years of suppressive ART were defined as INR and were compared to immunological responders (IR) with CD4 T-cell count >500 cells/mm 3 . Logistic and rank based regression were used to analyze clinical data, extensive innate and adaptive immunophenotyping, and ex vivo monocyte and lymphocyte cytokine production after stimulation with various stimuli. Results The discovery cohort consisted of 62 INR and 1224 IR, the validation cohort of 26 INR and 243 IR. INR were older, had more advanced HIV disease before starting ART and had more frequently a history of non-AIDS related malignancy. INR had lower absolute CD4+ T-cell numbers in all subsets. Activated (HLA-DR+, CD38+) and exhausted (PD1+) subpopulations were proportionally increased in CD4 T-cells. Monocyte and granulocyte immunophenotypes were comparable. INR lymphocytes produced less IL-22, IFN-γ, IL-10 and IL-17 to stimuli. In contrast, monocyte cytokine production did not differ. The proportions of CD4+CD38+HLA-DR+ and CD4+PD1+ subpopulations showed an inversed correlation to lymphocyte cytokine production. Conclusions INR compared to IR have hyperactivated and exhausted CD4+ T-cells in combination with lymphocyte functional impairment, while innate immune responses were comparable. Our data provide a rationale to consider the use of anti-PD1 therapy in INR.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- HIV immunological non-responders are characterized by extensive immunosenescence and impaired lymphocyte cytokine production capacity
- Date Crossref
- 08/05/2024
- Éditeur
- Frontiers Media SA
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Radboud University Nijmegen Donders Institute for Brain pays non établi dans la noticeUniversité ou école supérieure
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Radboud University Medical Center Department of Internal Medicine pays non établi dans la noticeOrganisme public
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OLVG pays non établi dans la noticeÉtablissement de santé
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Elisabeth-TweeSteden Ziekenhuis pays non établi dans la noticeÉtablissement de santé
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Erasmus MC pays non établi dans la noticeÉtablissement de santé
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Erasmus University Rotterdam Department of Internal Medicine pays non établi dans la noticeUniversité ou école supérieure
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Iuliu Hațieganu University of Medicine and Pharmacy Department of Medical Genetics pays non établi dans la noticeUniversité ou école supérieure
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University of Bonn Department of Immunology and Metabolism pays non établi dans la noticeUniversité ou école supérieure
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Department of Internal Medicine and Infectious Diseases pays non établi dans la noticeInstitution
Donders Institute for Brain — Radboud University Nijmegen, Department of Internal Medicine — Radboud University Medical Center et OLVG, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.