Vanesa Garrido‐RodríguezÁngel Bulnes‐RamosIsrael Olivas-MartínezMaría del Mar Pozo‐BaladoFrancisco TejerinaFélix GutiérrezCristina Marco‐SánchezJuan TiraboschiAntonia María Castillo-NavarroEnrique Bernal2026-03-222026-03-22202510.3389/fimmu.2025.1617674https://doi.org/10.3389/fimmu.2025.1617674https://andeanlibrary.org/handle/123456789/77826A 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.enCD4-CD8 RatioEffectorCD8Immune systemHomeostasisCytotoxic T cellPhenotypeHuman immunodeficiency virus (HIV)MetabolismBiologyarticle