title: Does an index composed of clinical data reflect effects of inflammation, coagulation, and monocyte activation on mortality among those aging with HIV?
abstract: BACKGROUND
  When added to age, CD4 count and human immunodeficiency virus type 1 (HIV-1) RNA alone (Restricted Index), hemoglobin, FIB-4 Index, hepatitis C virus (HCV), and estimated glomerular filtration rate improve prediction of mortality. Weighted and combined, these 7 routine clinical variables constitute the Veterans Aging Cohort Study (VACS) Index. Because nonroutine biomarkers of inflammation (interleukin 6 [IL-6]), coagulation (D-dimer), and monocyte activation (sCD14) also predict mortality, we test the association of these indices and biomarkers with each other and with mortality.
  
  
  METHODS
  Samples from 1302 HIV-infected veterans on antiretroviral therapy were analyzed. Indices were calculated closest to date of collection. We calculated Spearman correlations stratified by HIV-1 RNA and HCV status and measured association with mortality using C statistics and net reclassification improvement (NRI).
  
  
  RESULTS
  Of 1302 subjects, 915 had HIV-1 RNA <500 copies/mL and 154 died. The VACS Index was more correlated with IL-6, D-dimer, and sCD14 than the Restricted Index (P < .001). It was also more predictive of mortality (C statistic, 0.76; 95% confidence interval [CI], .72-.80) than any biomarker (C statistic, 0.66-0.70) or the Restricted Index (C statistic, 0.71; 95% CI, .67-.75). Compared to the Restricted Index alone, NRI resulted from incremental addition of VACS Index components (10%), D-dimer (7%), and sCD14 (4%), but not from IL-6 (0%).
  
  
  CONCLUSIONS
  Among HIV-infected individuals, independent of CD4, HIV-1 RNA, and age, hemoglobin and markers of liver and renal injury are associated with inflammation. Addition of D-dimer and sCD14, but not IL-6, improves the predictive accuracy of the VACS Index for mortality.
authors.affiliation: Veterans Affairs Connecticut Healthcare System, West Haven, CT 06516, USA. amy.justice2@va.gov
authors.forename: Amy C
authors.initials: AC
authors.lastname: Justice
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Freiberg
authors.forename: Russ
authors.initials: R
authors.lastname: Tracy
authors.forename: Lew
authors.initials: L
authors.lastname: Kuller
authors.forename: Janet P
authors.initials: JP
authors.lastname: Tate
authors.forename: Matthew Bidwell
authors.initials: MB
authors.lastname: Goetz
authors.forename: David A
authors.initials: DA
authors.lastname: Fiellin
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Vanasse
authors.forename: Adeel A
authors.initials: AA
authors.lastname: Butt
authors.forename: Maria C
authors.initials: MC
authors.lastname: Rodriguez-Barradas
authors.forename: Cynthia
authors.initials: C
authors.lastname: Gibert
authors.forename: Kris Ann
authors.initials: KA
authors.lastname: Oursler
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Kendall
authors.initials: K
authors.lastname: Bryant
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D015415:Biomarkers / Q000097:blood*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D015658:HIV Infections / Q000175:diagnosis* / Q000401:mortality* / Q000473:pathology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; C036309:fibrin fragment D