title: Evidence for innate immune system activation in HIV type 1-infected elite controllers.
abstract: BACKGROUND
  Elite controllers maintain high CD4(+) T-cell counts and suppress plasma human immunodeficiency virus (HIV) viremia in the absence of antiretroviral therapy (ART). It is unclear whether levels of biomarkers associated with coagulation, monocyte activation, and inflammation, which are linked to HIV-associated mortality, differ among elite controllers, ART recipients with suppressed viremia (plasma HIV type 1 RNA load, <50 copies/mL), and HIV-negative controls.
  
  
  METHODS
  A total of 68 elite controllers, 68 ART recipients with suppressed viremia, and 35 HIV-negative participants were evaluated. Levels of biomarkers in cryopreserved plasma were measured by enzyme-linked immunosorbent assay and electrochemiluminescence-based assay. Cryopreserved peripheral blood mononuclear cells were used to assess monocyte phenotype and function and interferon-inducible gene expression (IFIG). Nonparametric testing was used to compare median values among groups.
  
  
  RESULTS
  CD4(+) T-cell counts were similar between elite controllers and HIV-negative controls but significantly lower in ART recipients with suppressed viremia. Levels of C-reactive protein and interleukin 6 were higher and IFIG upregulated in both HIV-positive groups, compared with HIV-negative controls. D-dimer and soluble tissue factor levels were significantly elevated in elite controllers, compared with those in ART recipients with suppressed viremia and HIV-negative controls (P < .01). Monocytes from elite controllers (and ART recipients with suppressed viremia) expressed lower CCR2 and higher CX3CR1 levels than monocytes from HIV-negative controls. In addition, elite controllers had a significantly higher proportion of CD14(++)CD16(+) monocytes, compared with HIV-negative controls.
  
  
  CONCLUSIONS
  Elite controllers maintain control of plasma HIV viremia and have evidence of an activated innate immune response.
authors.affiliation: Clinical Research Directorate/Clinical Monitoring Research Program.
authors.forename: Sonya
authors.initials: S
authors.lastname: Krishnan
authors.forename: Eleanor M P
authors.initials: EM
authors.lastname: Wilson
authors.forename: Virginia
authors.initials: V
authors.lastname: Sheikh
authors.forename: Adam
authors.initials: A
authors.lastname: Rupert
authors.forename: Daniel
authors.initials: D
authors.lastname: Mendoza
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Richard
authors.initials: R
authors.lastname: Lempicki
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Migueles
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000097:blood*; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D015870:Gene Expression; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D018709:Statistics, Nonparametric; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D015415:Biomarkers; D016207:Cytokines; D005338:Fibrin Fibrinogen Degradation Products; D008070:Lipopolysaccharides; C036309:fibrin fragment D; D002097:C-Reactive Protein
keywords: Biomarkers; D-dimer; Elite Controllers; HIV; Monocytes; soluble Tissue Factor