The CD4/CD8 ratio in HIV-infected subjects is independently associated with T-cell activation despite long-term viral suppression

• Published in: The Journal of infection Vol. 66; no. 1; pp. 57 - 66
• Main Authors: Serrano-Villar, Sergio, Gutiérrez, Carolina, Vallejo, Alejandro, Hernández-Novoa, Beatriz, Díaz, Laura, Abad Fernández, María, Madrid, Nadia, Dronda, Fernando, Zamora, Javier, Muñoz-Fernández, María Ángeles, Moreno, Santiago
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.01.2013; Elsevier
• Subjects: Adult; Anti-Retroviral Agents - therapeutic use; antiretroviral therapy; Bacterial Translocation; Biological and medical sciences; CD4 antigen; CD4 count; CD4-CD8 Ratio; CD57 antigen; CD8 antigen; Clinical Trials, Phase II as Topic; Cross-Sectional Studies; Cyclohexanes - therapeutic use; Female; General aspects; Histocompatibility antigen HLA; HIV; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - microbiology; HIV-1 latent reservoir; Host-Pathogen Interactions; Human immunodeficiency virus; Human viral diseases; Humans; Immune activation; Immune response; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunological memory; Immunopathology; Immunosenescence; Infectious Disease; Infectious diseases; Latent infection; Lipopolysaccharides; Lymphocyte Activation; Lymphocytes T; Male; Medical sciences; Middle Aged; Multivariate Analysis; Pyrrolidinones - therapeutic use; Raltegravir Potassium; Risk Factors; RNA; Senescence; Statistics, Nonparametric; T-Lymphocytes - immunology; Triazoles - therapeutic use; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; HIV; CD4/CD8 ratio; Immunosenescence; Immune activation; HIV-1 latent reservoir; CD4 count; Bacterial translocation; Infection; Immunopathology; Immunological investigation; Viral disease; T-Lymphocyte; AIDS; Immune deficiency; Long term
• ISSN: 0163-4453; 1532-2742; 1532-2742
• DOI: 10.1016/j.jinf.2012.09.013

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.