title: Reclassification of risk of death with the knowledge of D-dimer in a cohort of treated HIV-infected individuals.
abstract: OBJECTIVE
  To evaluate the change in categories of risk of death by adding D-dimer to conventional mortality risk factors.
  
  
  METHODS
  Cohort study.
  
  
  METHODS
  Data on HIV-infected participants receiving standard combination antiretroviral therapy in two clinical trials (Evaluation of Subcutaneous Proleukin in a Randomized International Trial and Strategic Management of antiretroviral therapy), who had baseline D-dimer measured, were randomly split into two equal training and a validation datasets. A multivariable survival model was built using the training dataset and included only conventional mortality risk factors measured at baseline. D-dimer was added to create the comparison model. The level of reclassification of mortality risk, for those with at least 5-years of follow-up, was then assessed by tabulating mortality risk defined as low (≤2% predicted rate), moderate (2-5%) or high (>5%). Reclassification analyses were then repeated on the validation dataset.
  
  
  RESULTS
  The analysis population at baseline had a mean age of 43 years, median CD4(+) cell count of 535 cells/μl (IQR: 420-712), and 83% had HIV RNA of at least 500 copies/ml. In the training dataset (n=1946, 8939 person-years), there were 83 deaths at a rate of 0.93 per 100 person-years. Addition of D-dimer to the reference model resulted in 6% or fewer (P>0.05) being correctly reassigned, either up or down, to a new risk category, in both, training and validation datasets. The integrated discrimination improvement in training and validation datasets was 0.60% (P=0.084) and 0.45% (P=0.168), respectively.
  
  
  CONCLUSIONS
  In this relatively well population, at the given risk cutoffs, D-dimer appeared to only modestly improve the discernment of risk. Risk reclassification provides a method for assessing the clinical utility of biomarkers in HIV cohort studies.
authors.affiliation: The Kirby Institute for Infection and Immunity in society, University of New South Wales, Sydney, Australia. aachhra@kirby.unsw.edu.au
authors.forename: Amit C
authors.initials: AC
authors.lastname: Achhra
authors.forename: Janaki
authors.initials: J
authors.lastname: Amin
authors.forename: Caroline
authors.initials: C
authors.lastname: Sabin
authors.forename: Haitao
authors.initials: H
authors.lastname: Chu
authors.forename: David
authors.initials: D
authors.lastname: Dunn
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Kuller
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kovacs
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: Sean
authors.initials: S
authors.lastname: Emery
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Law
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000188:drug therapy / Q000401:mortality*; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D012367:RNA, Viral; C036309:fibrin fragment D