title: Circulating interleukin-6 levels correlate with residual HIV viraemia and markers of immune dysfunction in treatment-controlled HIV-infected patients.
abstract: BACKGROUND
  Antiretroviral therapy (ART)-controlled HIV-infected patients have elevated levels of systemic inflammatory markers, C-reactive protein (CRP) and interleukin (IL)-6, which correlate with increased cardiovascular risk and/or mortality. Persistent low-level viral replication could be involved in this inflammatory state. We evaluated whether residual viral load (VL) correlated with the level of systemic inflammatory/immune markers in ART-controlled HIV-infected patients.
  
  
  METHODS
  We evaluated 122 antiretroviral-controlled patients with VL 1-500 copies/ml for circulating levels of high-sensitivity (hs)CRP, hsIL-6, IL-8, soluble (s)CD14 and soluble tumour necrosis factor (TNF) receptors, sTNFR1 and sTNFR2.
  
  
  RESULTS
  The patients were 80.3% men, the median age was 47 years, the median CD4(+) T-cell count was 519 cells/mm(3), the median nadir CD4(+) T-cell count was 180 cells/mm(3), the median VL was 28 copies/ml and the median body mass index was 23.3 kg/m(2). The median (range) values for IL-6, CRP, IL-8, sCD14, sTNFR1 and sTNFR2 were 0.685 pg/ml (0.15-5.46), 1.8 mg/l (0.2-9.7), 10.0 pg/ml (1.6-71.1), 1,174 ng/ml (214-3,145), 1,112 pg/ml (583-5,834) and 2,412 pg/ml (1,142-7,688), respectively. IL-6 values correlated positively with HIV VL (rho=0.217, P=0.017). The VL threshold value for significantly increased IL-6 was 31 copies/ml (P=0.023). IL-6 values correlated with markers of immune dysfunction: the CD4/CD8 ratio (rho=-0.248, P=0.011), CD4 nadir level (rho=-0.186, P=0.04) and nadir CD4/CD8 ratio (rho=-0.257, P=0.008). They negatively correlated with markers of immune activation sCD14 (rho=-0.236, P=0.011) and IL-8 (rho=-0.290, P=0.002). We found no correlation between VL and CRP or other markers of inflammation/immune dysfunction including sTNFR1, sTNFR2, sCD14 and IL-8.
  
  
  CONCLUSIONS
  We report here that low-range IL-6 levels correlated with low-range VL and inversely with sCD14 and IL-8. Our findings suggest that maintaining VL<30 copies/ml in HIV-infected patients might therefore reduce IL-6.
authors.affiliation: UPMC Université de Paris 06, UMR_S938, INSERM, CDR Saint-Antoine, Paris, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Bastard
authors.forename: Cathia
authors.initials: C
authors.lastname: Soulié
authors.forename: Soraya
authors.initials: S
authors.lastname: Fellahi
authors.forename: Stephanie
authors.initials: S
authors.lastname: Haïm-Boukobza
authors.forename: Anne
authors.initials: A
authors.lastname: Simon
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
authors.forename: Anne-Geneviève
authors.initials: AG
authors.lastname: Marcelin
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Capeau
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D016209:Interleukin-8 / Q000097:blood / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008297:Male; D008875:Middle Aged; D019562:Viral Load; D014766:Viremia / Q000276:immunology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D002097:C-Reactive Protein