Journal of Microbiology, Immunology and Infection (Dec 2024)

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

  • 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

Journal volume & issue
Vol. 57, no. 6
pp. 854 – 867

Abstract

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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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