HIV-infected subjects on antiretroviral therapy often fail to normalize the CD4/CD8 ratio despite CD4 count normalization. We aimed to analyze the biological significance of this finding.

Cross-sectional analysis in 20 HIV-infected subjects on stable triple-ART, plasma HIV RNA <40 copies/mL for at least 2 years and CD4 count >350 cells/mm³. Laboratory measurements included T-cell activation (HLADR⁺, CD38⁺) and senescence (CD57⁺), lipopolysaccharide (LPS), sCD14 and the HIV latent reservoir (number of latently infected memory CD4 cells carrying replication-competent virus).

CD4/CD8 ratio was positively correlated with CD4 nadir (r = 0.468, p = 0.038) and accumulated ART exposure (r = 0.554, p = 0.0011), and negatively with viral load before ART initiation (r = −0.547, p = 0.013), CD4⁺HLADR⁺CD38⁺ T-cells (r = −0.428, p = 0.086) and CD8⁺CD57⁺ T-cells (r = −0.431, p = 0.084). No associations with LPS, sCD14 or HIV latent reservoir were found. After the multivariate analyses, the CD4/CD8 ratio remained independently associated with CD4⁺HLADR⁺CD38⁺ T-cells and CD8⁺HLADR⁺ T-cells.

In our study in subjects on suppressive ART the CD4/CD8 ratio was independently associated with T-cell activation. Our results must be confirmed in larger studies, as this parameter might be a useful clinical tool to identify subjects with ongoing immune activation despite long-term viral suppression.