The persistence of low CD4/CD8 ratio in chronic HIV-infection, despite ART suppression and normal CD4 levels, is associated with pre-therapy values of inflammation and thymic function

Autor: Vanesa Garrido-Rodríguez, Ángel Bulnes-Ramos, Israel Olivas-Martínez, María del Mar Pozo-Balado, Ana Isabel Álvarez-Ríos, Félix Gutiérrez, Rebeca Izquierdo, Federico García, Juan Manuel Tiraboschi, Francisco Vera-Méndez, Joaquim Peraire, Anna Rull, Yolanda María Pacheco
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Journal of Microbiology, Immunology and Infection, Vol 57, Iss 6, Pp 854-867 (2024)
Druh dokumentu: article
ISSN: 1684-1182
DOI: 10.1016/j.jmii.2024.08.007
Popis: Background: Persistence of a low CD4/CD8 ratio is associated with an increased morbimortality in people living with HIV (PLWH) under effective antiretroviral therapy. We aimed to explore the immunological significance of a persistently low CD4/CD8 ratio, even despite normal CD4 levels, and assess whether these features vary from those associated to a low nadir-CD4, another well-established predictor of disease progression. Methods: CD4-recovered PLWH were classified by CD4/CD8 ratio after three-years of ART (viral suppression, CD4≥500; R 1.2, n = 28). sj/β-TRECs ratio and inflammatory-related markers were quantified. PBMCs were immunophenotyped by CyTOF and functionally characterized by ELISPOT. Subjects were also reclassified depending on nadir-CD4 (N ≤ 350/N > 350). Results: R 1.2 (increased β2-microglobulin, D-dimers and IP-10 before ART). R 350, the main features were altered functional markers in CD4 T-cells, despite no differences in maturational subsets, together with a restricted T-cell cytokine secretion pattern. Conclusion: Persistence of low CD4/CD8 ratio in successfully-treated PLWH, with normal CD4 counts, is associated with baseline inflammation and low thymic function, and it features post-therapy alterations specific to CD8 T-cells. Differently, subjects recovered from low nadir-CD4 in this setting feature post-therapy alterations on CD4 T-cells. Hence, different mechanisms of disease progression could underlie these biomarkers, potentially requiring different clinical approaches.
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