title: Predictive accuracy of the Veterans Aging Cohort Study index for mortality with HIV infection: a North American cross cohort analysis.
abstract: BACKGROUND
  By supplementing an index composed of HIV biomarkers and age (restricted index) with measures of organ injury, the Veterans Aging Cohort Study (VACS) index more completely reflects risk of mortality. We compare the accuracy of the VACS and restricted indices (1) among subjects outside the Veterans Affairs Healthcare System, (2) more than 1-5 years of prior exposure to antiretroviral therapy (ART), and (3) within important patient subgroups.
  
  
  METHODS
  We used data from 13 cohorts in the North American AIDS Cohort Collaboration (n = 10, 835) limiting analyses to HIV-infected subjects with at least 12 months exposure to ART. Variables included demographic, laboratory (CD4 count, HIV-1 RNA, hemoglobin, platelets, aspartate and alanine transaminase, creatinine, and hepatitis C status), and survival. We used C-statistics and net reclassification improvement (NRI) to test discrimination varying prior ART exposure from 1 to 5 years. We then combined Veterans Affairs Healthcare System (n = 5066) and North American AIDS Cohort Collaboration data, fit a parametric survival model, and compared predicted to observed mortality by cohort, gender, age, race, and HIV-1 RNA level.
  
  
  RESULTS
  Mean follow-up was 3.3 years (655 deaths). Compared with the restricted index, the VACS index showed greater discrimination (C-statistics: 0.77 vs. 0.74; NRI: 12%; P < 0.0001). NRI was highest among those with HIV-1 RNA <500 copies per milliliter (25%) and age ≥50 years (20%). Predictions were similar to observed mortality among all subgroups.
  
  
  CONCLUSIONS
  VACS index scores discriminate risk and translate into accurate mortality estimates over 1-5 years of exposure to ART and for diverse patient subgroups from North American.
authors.affiliation: Department of Internal Medicine, Yale University and the Veterans Affairs Healthcare System, West Haven, CT 06516, USA. amy.justice2@va.gov
authors.forename: Amy C
authors.initials: AC
authors.lastname: Justice
authors.forename: Sharada P
authors.initials: SP
authors.lastname: Modur
authors.forename: Janet P
authors.initials: JP
authors.lastname: Tate
authors.forename: Keri N
authors.initials: KN
authors.lastname: Althoff
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Jacobson
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Gebo
authors.forename: Mari M
authors.initials: MM
authors.lastname: Kitahata
authors.forename: Michael A
authors.initials: MA
authors.lastname: Horberg
authors.forename: John T
authors.initials: JT
authors.lastname: Brooks
authors.forename: Kate
authors.initials: K
authors.lastname: Buchacz
authors.forename: Sean B
authors.initials: SB
authors.lastname: Rourke
authors.forename: Anita
authors.initials: A
authors.lastname: Rachlis
authors.forename: Sonia
authors.initials: S
authors.lastname: Napravnik
authors.forename: Joseph
authors.initials: J
authors.lastname: Eron
authors.forename: James H
authors.initials: JH
authors.lastname: Willig
authors.forename: Richard
authors.initials: R
authors.lastname: Moore
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Kirk
authors.forename: Ronald
authors.initials: R
authors.lastname: Bosch
authors.forename: Benigno
authors.initials: B
authors.lastname: Rodriguez
authors.forename: Robert S
authors.initials: RS
authors.lastname: Hogg
authors.forename: Jennifer
authors.initials: J
authors.lastname: Thorne
authors.forename: James J
authors.initials: JJ
authors.lastname: Goedert
authors.forename: Marina
authors.initials: M
authors.lastname: Klein
authors.forename: John
authors.initials: J
authors.lastname: Gill
authors.forename: Steven
authors.initials: S
authors.lastname: Deeks
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Sterling
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gange
mesh_terms: D000367:Age Factors; D000410:Alanine Transaminase / Q000097:blood; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000208:ethnology / Q000276:immunology / Q000401:mortality*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006454:Hemoglobins / Q000378:metabolism; D006526:Hepatitis C / Q000097:blood / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009656:North America / Q000453:epidemiology; D010976:Platelet Count; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood; D018570:Risk Assessment / Q000379:methods; D012737:Sex Factors
chemical_list: D044966:Anti-Retroviral Agents; D015415:Biomarkers; D006454:Hemoglobins; D012367:RNA, Viral; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase