title: Frailty, Inflammation, and Mortality Among Persons Aging With HIV Infection and Injection Drug Use.
abstract: BACKGROUND
  Serum markers of inflammation increase with age and have been strongly associated with adverse clinical outcomes among both HIV-infected and uninfected adults. Yet, limited data exist on the predictive and clinical utility of aggregate measures of inflammation. This study sought to evaluate the relationship of a recently validated aggregate inflammatory index with frailty and mortality among aging HIV-infected and uninfected injection drug users.
  
  
  METHODS
  Frailty was assessed among HIV-infected and uninfected participants in the AIDS Linked to the IntraVenous Experience (ALIVE) cohort study using the five Fried phenotypic criteria: weight loss, exhaustion, low physical activity, decreased grip strength, and slow gait. The aggregate inflammatory index was constructed from serum measures of interleukin-6 and soluble tumor necrosis factor-α receptor-1. Multinomial logistic regression was used to assess the relationship of frailty with inflammation. Cox proportional hazards models were used to estimate risk for all-cause mortality.
  
  
  RESULTS
  Among 1,326 subjects, the median age was 48 years and 29% were HIV-infected. Adjusting for sociodemographics, comorbidity, and HIV status, frailty was significantly associated with each standard deviation increase in log interleukin-6 (odds ratio 1.33; 95% CI, 1.09-1.61), log tumor necrosis factor-α receptor-1 (odds ratio 1.25; 95% CI, 1.04-1.51) and inflammatory index score (odds ratio 1.39; 95% CI, 1.14-1.68). Adjusting for sociodemographics, comorbidity, HIV status, and frailty, the inflammatory index score was independently associated with increased mortality (HR 1.65; 95% CI, 1.44-1.89).
  
  
  CONCLUSIONS
  A recently validated, simple, biologically informed inflammatory index is independently associated with frailty and mortality risk among aging HIV-infected and uninfected injection drug users.
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, Maryland. dpiggot1@jhmi.edu.
authors.forename: Damani A
authors.initials: DA
authors.lastname: Piggott
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Ravi
authors.initials: R
authors.lastname: Varadhan
authors.affiliation: Department of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, Maryland.
authors.forename: Shruti H
authors.initials: SH
authors.lastname: Mehta
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, Maryland.
authors.forename: Todd T
authors.initials: TT
authors.lastname: Brown
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Huifen
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Walston
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Sean X
authors.initials: SX
authors.lastname: Leng
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Kirk
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging; D005260:Female; D016330:Frail Elderly; D015658:HIV Infections / Q000097:blood / Q000150:complications* / Q000401:mortality*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood; D015819:Substance Abuse, Intravenous / Q000097:blood / Q000150:complications* / Q000401:mortality*
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D047888:Receptors, Tumor Necrosis Factor, Type I
keywords: Frailty; HIV; Inflammation; Injection drug use; Mortality