2026-04-19T13:35:55Zhttps://recercat.cat/oai/request
oai:recercat.cat:2445/2236612025-11-19T22:46:06Zcom_2072_1057col_2072_478916col_2072_478917
RECERCAT author Garrido Rodríguez, Vanesa author Bulnes Ramos, Ángel author Olivas Martínez, Israel author Mar Pozo Balado, María del author Tejerina-Picado, Francisco author Gutiérrez, Félix author Marco Sánchez, Cristina author Tiraboschi, Juan Manuel author Castillo Navarro, Antonia author Bernal, Enrique author García Guerrero, María C. author Puertas Castro, Ma. Carmen author Peraire, Joaquim author Rull, Anna author Martínez Picado, Francisco Javier author Pacheco, Yolanda María author CoRIS cohort 2025-11-19T22:46:05Z 2025-11-19T22:46:05Z 2025-10-15T07:16:51Z2025-10-15T07:16:51Z2025-09-082025-10-14T09:11:04Z http://hdl.handle.net/2445/223661 Background: People living with chronic HIV (PLWH) show immune dysfunction, despite viral suppression and normal CD4 recovery, particularly those with low CD4/CD8 ratios. Subjacent cellular alterations of such a reliable marker of clinical progression remain elusive. Methods: Categorization by CD4/CD8 ratio after three year of therapy (R < 0.8/R > 1.2, n = 28/n = 24) and post-hoc reclassification by nadir-CD4 (N <= 350/N > 350) were performed in PLWH achieving viral suppression and CD4 >= 500. CD4 T cell-associated viral reservoir, as well as metabolism-related gene expression, glucose uptake ability, relative telomere length (RTL), and thymic output for CD4 and CD8 T cells, were determined. Results: Patients with a CD4/CD8 ratio < 0.8 exhibited reduced CD8 T-cell glucose uptake ability after stimulation (p = 0.007) and trends to shorter RTL (p = 0.093) and to larger CD4-associated viral reservoir (p = 0.068) than R > 1.2. Differently, patients with nadir <= 350 exhibited altered CD4 and CD8 T-cell expression of metabolism-related genes, although no differences in glucose uptake ability, and shorter RTL in both cell subsets, but similar viral reservoir to patients with nadir >350. Remarkably, viral reservoir and both CD4 and CD8 thymic output showed inverse associations (r = -0.623, p = 0.01 and r = -0.661, p = 0.038, respectively). Conclusion: A low CD4/CD8 ratio in chronic PLWH stands on a larger viral reservoir in CD4 T cells and metabolic alterations in CD8 T cells, probably related to its exhaustion and compromised effector functionality, and thymic output could contribute to such alterations. Patients with lower nadir-CD4 showed a resting-like CD4 phenotype and a metabolically active CD8 subset, without further viral reservoir extension. Persistence of low CD4/CD8 ratio and low nadir-CD4 counts seems to rely on different immune damage. cc-by (c) Garrido Rodríguez, Vanesa et al., 2025 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Cèl·lules T Immunopatologia VIH (Virus) T cells Immunopathology HIV (Viruses) Unveiling altered CD8 T-cell metabolism and homeostatic proliferation behind a low CD4/CD8 ratio in ART-suppressed HIV individuals with normal CD4 recovery info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion