title: Pretreatment levels of soluble cellular receptors and interleukin-6 are associated with HIV disease progression in subjects treated with highly active antiretroviral therapy.
abstract: BACKGROUND
  To identify inflammatory pathways that may contribute to the pathogenesis of human immunodeficiency virus (HIV) disease, we explored associations between AIDS or death and different inflammatory markers, including selected soluble tumor necrosis factor superfamily receptors (sTNFRs) and ligands, interleukin (IL)-6, and CD8 T cell activation, in individuals treated with highly active antiretroviral therapy (HAART).
  
  
  METHODS
  A case-control study of subjects in AIDS Clinical Trials Group (ACTG) protocols 384 and 5015, who were matched according to the CD4 cell count and plasma viral load at baseline, was performed using conditional logistic regression.
  
  
  RESULTS
  Higher pretreatment concentrations of sTNFR-1, sCD27, sCD40L, and plasma IL-6 were associated with a new AIDS-defining illness or death in separate models adjusted for age, sex, hemoglobin, and the latest CD4 cell counts. In additional models that excluded case patients with opportunistic infections, sTNFR-1, sCD27, and sCD40L were each associated with a new AIDS-defining malignancy or death that developed at a median of 51 weeks after initiation of HAART, by which time the majority of subjects had a CD4 cell count of >200 cells/cm(3) and had achieved a plasma viral load of <50 copies/mL.
  
  
  CONCLUSIONS
  These data are compatible with a model in which these soluble inflammatory markers identify pathways that may contribute to the pathogenesis of HIV disease progression, pathways that might not be a direct consequence of ongoing HIV type 1 replication.
authors.affiliation: MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio 44109-1998, USA. rkalayjian@metrohealth.org
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kalayjian
authors.forename: Rhoderick N
authors.initials: RN
authors.lastname: Machekano
authors.forename: Nesrine
authors.initials: N
authors.lastname: Rizk
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Robbins
authors.forename: Rajesh T
authors.initials: RT
authors.lastname: Gandhi
authors.forename: Benigno A
authors.initials: BA
authors.lastname: Rodriguez
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pollard
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor
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