We explored the associations of the CD4/CD8 ratio with markers of immunoactivation, immunosenescence and T-cell subsets, in 37 vertically HIV-infected children and adolescents. CD4/CD8 ratio inversion was associated with higher frequencies of activated, senescent and activated/exhausted CD4and CD8 T-cells, and a skewed T-cell phenotype from naïve toward effector memory which persisted after the multivariate analysis. Thus, the CD4/CD8 ratio may identify subjects with higher immunoactivation despite ART.