title: The VACS index accurately predicts mortality and treatment response among multi-drug resistant HIV infected patients participating in the options in management with antiretrovirals (OPTIMA) study.
abstract: OBJECTIVE
  The VACS Index is highly predictive of all-cause mortality among HIV infected individuals within the first few years of combination antiretroviral therapy (cART). However, its accuracy among highly treatment experienced individuals and its responsiveness to treatment interventions have yet to be evaluated. We compared the accuracy and responsiveness of the VACS Index with a Restricted Index of age and traditional HIV biomarkers among patients enrolled in the OPTIMA study.
  
  
  METHODS
  Using data from 324/339 (96%) patients in OPTIMA, we evaluated associations between indices and mortality using Kaplan-Meier estimates, proportional hazards models, Harrel's C-statistic and net reclassification improvement (NRI). We also determined the association between study interventions and risk scores over time, and change in score and mortality.
  
  
  RESULTS
  Both the Restricted Index (c = 0.70) and VACS Index (c = 0.74) predicted mortality from baseline, but discrimination was improved with the VACS Index (NRI = 23%). Change in score from baseline to 48 weeks was more strongly associated with survival for the VACS Index than the Restricted Index with respective hazard ratios of 0.26 (95% CI 0.14-0.49) and 0.39(95% CI 0.22-0.70) among the 25% most improved scores, and 2.08 (95% CI 1.27-3.38) and 1.51 (95%CI 0.90-2.53) for the 25% least improved scores.
  
  
  CONCLUSIONS
  The VACS Index predicts all-cause mortality more accurately among multi-drug resistant, treatment experienced individuals and is more responsive to changes in risk associated with treatment intervention than an index restricted to age and HIV biomarkers. The VACS Index holds promise as an intermediate outcome for intervention research.
authors.affiliation: James J. Peters VA Medical Center, Bronx, New York, United States of America; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Sheldon T
authors.initials: ST
authors.lastname: Brown
authors.affiliation: Section of General Internal Medicine, VA Connecticut Healthcare System, West Haven, Connecticut, United States of America; Yale University Schools of Medicine and Public Health, New Haven, Connecticut, United States of America.
authors.forename: Janet P
authors.initials: JP
authors.lastname: Tate
authors.affiliation: VA Cooperative Studies Program Coordinating Center, VA Connecticut Healthcare System, West Haven, Connecticut, United States of America.
authors.forename: Tassos C
authors.initials: TC
authors.lastname: Kyriakides
authors.affiliation: VA Cooperative Studies Program Coordinating Center, VA Connecticut Healthcare System, West Haven, Connecticut, United States of America.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Kirkwood
authors.affiliation: VA Palo Alto Healthcare System, Palo Alto, California, United States of America; Department of Medicine, Stanford University School of Medicine, Palo Alto, California, United States of America.
authors.forename: Mark
authors.initials: M
authors.lastname: Holodniy
authors.affiliation: Section of General Internal Medicine, VA Connecticut Healthcare System, West Haven, Connecticut, United States of America; Yale University Schools of Medicine and Public Health, New Haven, Connecticut, United States of America.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Goulet
authors.affiliation: Nuffield Department of Medicine, Oxford University, Oxford, United Kingdom.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Angus
authors.affiliation: University of Ottawa at the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: D William
authors.initials: DW
authors.lastname: Cameron
authors.affiliation: Section of General Internal Medicine, VA Connecticut Healthcare System, West Haven, Connecticut, United States of America; Yale University Schools of Medicine and Public Health, New Haven, Connecticut, United States of America.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Justice
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D024921:Drug Resistance, Multiple, Viral; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011237:Predictive Value of Tests; D012307:Risk Factors
chemical_list: D015415:Biomarkers