title: Towards a combined prognostic index for survival in HIV infection: the role of 'non-HIV' biomarkers.
abstract: BACKGROUND
  As those with HIV infection live longer, 'non-AIDS' condition associated with immunodeficiency and chronic inflammation are more common. We ask whether 'non-HIV' biomarkers improve differentiation of mortality risk among individuals initiating combination antiretroviral therapy (cART).
  
  
  METHODS
  Using Poisson models, we analysed data from the Veterans Aging Cohort Study (VACS) on HIV-infected veterans initiating cART between 1 January 1997 and 1 August 2002. Measurements included: HIV biomarkers (CD4 cell count, HIV RNA and AIDS-defining conditions); 'non-HIV' biomarkers (haemoglobin, transaminases, platelets, creatinine, and hepatitis B and C serology); substance abuse or dependence (alcohol or drug); and age. Outcome was all cause mortality. We tested the discrimination (C statistics) of each biomarker group alone and in combination in development and validation data sets, over a range of survival intervals, and adjusting for missing data.
  
  
  RESULTS
  Of veterans initiating cART, 9784 (72%) had complete data. Of these, 2566 died. Subjects were middle-aged (median age 45 years), mainly male (98%) and predominantly black (51%). HIV and 'non-HIV' markers were associated with each other (P < 0.0001) and discriminated mortality (C statistics 0.68-0.73); when combined, discrimination improved (P < 0.0001). Discrimination for the VACS Index was greater for shorter survival intervals [30-day C statistic 0.86, 95% confidence interval (CI) 0.80-0.91], but good for intervals of up to 8 years (C statistic 0.73, 95% CI 0.72-0.74). Results were robust to adjustment for missing data.
  
  
  CONCLUSIONS
  When added to HIV biomarkers, 'non-HIV' biomarkers improve differentiation of mortality. When evaluated over similar intervals, the VACS Index discriminates as well as other established indices. After further validation, the VACS Index may provide a useful, integrated risk assessment for management and research.
authors.affiliation: Section of General Internal Medicine, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA. amy.justice2@va.gov
authors.forename: Amy C
authors.initials: AC
authors.lastname: Justice
authors.forename: K A
authors.initials: KA
authors.lastname: McGinnis
authors.forename: M
authors.initials: M
authors.lastname: Skanderson
authors.forename: C C
authors.initials: CC
authors.lastname: Chang
authors.forename: C L
authors.initials: CL
authors.lastname: Gibert
authors.forename: M B
authors.initials: MB
authors.lastname: Goetz
authors.forename: D
authors.initials: D
authors.lastname: Rimland
authors.forename: M C
authors.initials: MC
authors.lastname: Rodriguez-Barradas
authors.forename: K K
authors.initials: KK
authors.lastname: Oursler
authors.forename: S T
authors.initials: ST
authors.lastname: Brown
authors.forename: R S
authors.initials: RS
authors.lastname: Braithwaite
authors.forename: M
authors.initials: M
authors.lastname: May
authors.forename: K E
authors.initials: KE
authors.lastname: Covinsky
authors.forename: M S
authors.initials: MS
authors.lastname: Roberts
authors.forename: S L
authors.initials: SL
authors.lastname: Fultz
authors.forename: K J
authors.initials: KJ
authors.lastname: Bryant
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000453:epidemiology / Q000276:immunology; D000368:Aged; D000740:Anemia / Q000097:blood / Q000453:epidemiology; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D002423:Cause of Death; D015331:Cohort Studies; D016001:Confidence Intervals; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000401:mortality*; D020276:HIV Long-Term Survivors / Q000706:statistics & numerical data*; D006525:Hepatitis, Viral, Human / Q000453:epidemiology / Q000276:immunology; D006801:Humans; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012720:Severity of Illness Index; D019966:Substance-Related Disorders / Q000453:epidemiology; D016019:Survival Analysis
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D012367:RNA, Viral