title: The CD4/CD8 ratio in HIV-infected subjects is independently associated with T-cell activation despite long-term viral suppression.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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/mm(3). 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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Infectious Diseases Department, Hospital Universitario Ramón y Cajal, Madrid, Spain. serranovillar@gmail.com
authors.forename: Sergio
authors.initials: S
authors.lastname: Serrano-Villar
authors.forename: Carolina
authors.initials: C
authors.lastname: Gutiérrez
authors.forename: Alejandro
authors.initials: A
authors.lastname: Vallejo
authors.forename: Beatriz
authors.initials: B
authors.lastname: Hernández-Novoa
authors.forename: Laura
authors.initials: L
authors.lastname: Díaz
authors.forename: María
authors.initials: M
authors.lastname: Abad Fernández
authors.forename: Nadia
authors.initials: N
authors.lastname: Madrid
authors.forename: Fernando
authors.initials: F
authors.lastname: Dronda
authors.forename: Javier
authors.initials: J
authors.lastname: Zamora
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Muñoz-Fernández
authors.forename: Santiago
authors.initials: S
authors.lastname: Moreno
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D018988:Bacterial Translocation; D016516:CD4-CD8 Ratio; D017322:Clinical Trials, Phase II as Topic; D003430:Cross-Sectional Studies; D003510:Cyclohexanes / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000382:microbiology; D054884:Host-Pathogen Interactions; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D015999:Multivariate Analysis; D011760:Pyrrolidinones / Q000627:therapeutic use; D000068898:Raltegravir Potassium; D012307:Risk Factors; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology*; D014230:Triazoles / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D003510:Cyclohexanes; D011760:Pyrrolidinones; D014230:Triazoles; D000068898:Raltegravir Potassium; D000077592:Maraviroc