title: Soluble markers of inflammation and coagulation but not T-cell activation predict non-AIDS-defining morbid events during suppressive antiretroviral treatment.
abstract: BACKGROUND
  Defining the association of non-AIDS-defining events with inflammation and immune activation among human immunodeficiency virus (HIV)-infected persons with antiretroviral therapy (ART)-associated virological suppression is critical to identifying interventions to decrease the occurrence of these events.
  
  
  METHODS
  We conducted a case-control study of HIV-infected subjects who had achieved virological suppression within 1 year after ART initiation. Cases were patients who experienced non-AIDS-defining events, defined as myocardial infarction, stroke, non-AIDS-defining cancer, non-AIDS-defining serious bacterial infection, or death. Controls were matched to cases on the basis of age, sex, pre-ART CD4(+) T-cell count, and ART regimen. Peripheral blood mononuclear cells and plasma specimens obtained at the visit before ART initiation (hereafter, baseline), the visit approximately 1 year after ART initiation (hereafter, year 1), and the visit immediately preceding the non-AIDS-defining event (hereafter, pre-event) were analyzed for activated CD4(+) and CD8(+) T cells, plasma interleukin 6 (IL-6) level, soluble tumor necrosis factor receptor I (sTNFR-I) level, sTNFR-II level, soluble CD14 level, kynurenine-to-tryptophan (KT) ratio, and D-dimer level. Conditional logistic regression analysis was used to study the association between biomarkers and outcomes, with adjustment for potential confounders.
  
  
  RESULTS
  Higher IL-6 level, sTNFR-I level, sTNFR-II level, KT ratio, and D-dimer level at year 1 were associated with the occurrence of a non-AIDS-defining event. Significant associations were also seen between non-AIDS-defining events and values of these biomarkers in specimens obtained at baseline and the pre-event time points. Effects remained significant after control for confounders. T-cell activation was not significantly related to outcomes.
  
  
  CONCLUSIONS
  Interventional trials to decrease the incidence of non-AIDS-defining events among HIV-infected persons with virological suppression should consider targeting the pathways represented by these soluble markers. Clinical Trials Registration. NCT00001137.
authors.affiliation: Department of Medicine.
authors.forename: Allan R
authors.initials: AR
authors.lastname: Tenorio
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Bosch
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Supriya
authors.initials: S
authors.lastname: Krishnan
authors.affiliation: Division of Infectious Diseases and HIV Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio.
authors.forename: Benigno
authors.initials: B
authors.lastname: Rodriguez
authors.affiliation: Positive Health Program, Department of Medicine, San Francisco General Hospital, University of California;
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hunt
authors.affiliation: Department of Immunology and Microbiology, Rush University Medical Center, Chicago, Illinois.
authors.forename: Jill
authors.initials: J
authors.lastname: Plants
authors.affiliation: Division of Infectious Diseases and HIV Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio.
authors.forename: Arjun
authors.initials: A
authors.lastname: Seth
authors.affiliation: Division of Infectious Diseases, University of Colorado Hospital, Aurora.
authors.forename: Cara C
authors.initials: CC
authors.lastname: Wilson
authors.affiliation: Positive Health Program, Department of Medicine, San Francisco General Hospital, University of California;
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.affiliation: Division of Infectious Diseases and HIV Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.affiliation: Department of Immunology and Microbiology, Rush University Medical Center, Chicago, Illinois.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Landay
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D001777:Blood Coagulation / Q000502:physiology*; D016022:Case-Control Studies; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D013601:T-Lymphocytes / Q000502:physiology*; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D012367:RNA, Viral
keywords: ART; HIV; Non-AIDS morbidity; immune activation; inflammation