title: Interleukin 6 Is a Stronger Predictor of Clinical Events Than High-Sensitivity C-Reactive Protein or D-Dimer During HIV Infection.
abstract: BACKGROUND
  Interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and D-dimer levels are linked to adverse outcomes in human immunodeficiency virus (HIV) infection, but the strength of their associations with different clinical end points warrants investigation.
  
  
  METHODS
  Participants receiving standard of care in 2 HIV trials with measured biomarker levels were followed to ascertain all-cause death, non-AIDS-related death, AIDS, cardiovascular disease (CVD), and non-AIDS-defining malignancies. Hazard ratios (HRs) and 95% confidence intervals (CIs) of each end point for quartiles and log2-transformed IL-6, hsCRP, and D-dimer levels were calculated using Cox models. Marginal models modelling multiple events tested for equal effects of biomarker levels on different end points.
  
  
  RESULTS
  Among 4304 participants, there were 157 all-cause deaths, 117 non-AIDS-related deaths, 101 AIDS cases, 121 CVD cases, and 99 non-AIDS-defining malignancies. IL-6 was more strongly associated with most end points, compared with hsCRP. IL-6 appeared to be a stronger predictor than D-dimer for CVD and non-AIDS-defining malignancies, but 95% CIs overlapped. Independent associations of IL-6 were stronger for non-AIDS-related death (HR, 1.71; 95% CI, 1.43-2.04) and all-cause death (HR, 1.56; 95% CI, 1.33-1.84) and similar for CVD (HR, 1.35; 95% CI, 1.12-1.62) and non-AIDS-defining malignancies (HR, 1.30; 95% CI, 1.06-1.61). There was heterogeneity of IL-6 (P < .001) but not hsCRP (P = .15) or D-dimer (P = .20) as a predictor for different end points.
  
  
  CONCLUSIONS
  IL-6 is a stronger predictor of fatal events than of CVD and non-AIDS-defining malignancies. Adjuvant antiinflammatory and antithrombotic therapies should be tested in HIV-infected individuals.
authors.affiliation: Centre for Health and Infectious Diseases Research (CHIP), Department of Infectious Diseases, Rigshospitalet-University of Copenhagen, Denmark.
authors.forename: Álvaro H
authors.initials: ÁH
authors.lastname: Borges
authors.affiliation: Research Department of Infection and Population Health, University College London, United Kingdom;
authors.forename: Jemma L
authors.initials: JL
authors.lastname: O'Connor
authors.affiliation: Research Department of Infection and Population Health, University College London, United Kingdom;
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Phillips
authors.affiliation: Division of Biostatistics, School of Public Health.
authors.forename: James D
authors.initials: JD
authors.lastname: Neaton
authors.affiliation: School of Statistics, University of Minnesota, Minneapolis.
authors.forename: Birgit
authors.initials: B
authors.lastname: Grund
authors.affiliation: Division of Biostatistics, School of Public Health.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Neuhaus
authors.affiliation: Institute for Clinical Research Veterans Affairs Medical Center, Washington D.C.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Vjecha
authors.affiliation: HIV Unit, Division of Infectious Diseases, Geneva University Hospitals, Switzerland;
authors.forename: Alexandra
authors.initials: A
authors.lastname: Calmy
authors.affiliation: The Kirby Institute for Infection and Immunity in Society, University of New South Wales, and St. Vincent's Hospital, Sydney, Australia.
authors.forename: Kersten K
authors.initials: KK
authors.lastname: Koelsch
authors.affiliation: Centre for Health and Infectious Diseases Research (CHIP), Department of Infectious Diseases, Rigshospitalet-University of Copenhagen, Denmark.
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
mesh_terms: D000328:Adult; D000933:Antifibrinolytic Agents; D002097:C-Reactive Protein / Q000032:analysis*; D015331:Cohort Studies; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D015658:HIV Infections / Q000175:diagnosis* / Q000473:pathology*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012680:Sensitivity and Specificity; D016019:Survival Analysis
chemical_list: D000933:Antifibrinolytic Agents; D005338:Fibrin Fibrinogen Degradation Products; D015850:Interleukin-6; C036309:fibrin fragment D; D002097:C-Reactive Protein
keywords: D-dimer; HIV; IL-6; cancer; cardiovascular disease; hsCRP; inflammation