title: Injection Drug Use and Hepatitis C as Risk Factors for Mortality in HIV-Infected Individuals: The Antiretroviral Therapy Cohort Collaboration.
abstract: BACKGROUND
  HIV-infected individuals with a history of transmission through injection drug use (IDU) have poorer survival than other risk groups. The extent to which higher rates of hepatitis C (HCV) infection in IDU explain survival differences is unclear.
  
  
  METHODS
  Adults who started antiretroviral therapy between 2000 and 2009 in 16 European and North American cohorts with >70% complete data on HCV status were followed for 3 years. We estimated unadjusted and adjusted (for age, sex, baseline CD4 count and HIV-1 RNA, AIDS diagnosis before antiretroviral therapy, and stratified by cohort) mortality hazard ratios for IDU (versus non-IDU) and for HCV-infected (versus HCV uninfected).
  
  
  RESULTS
  Of 32,703 patients, 3374 (10%) were IDU; 4630 (14%) were HCV+; 1116 (3.4%) died. Mortality was higher in IDU compared with non-IDU [adjusted HR 2.71; 95% confidence interval (CI): 2.32 to 3.16] and in HCV+ compared with HCV- (adjusted HR 2.65; 95% CI: 2.31 to 3.04). The effect of IDU was substantially attenuated (adjusted HR 1.57; 95% CI: 1.27 to 1.94) after adjustment for HCV, while attenuation of the effect of HCV was less substantial (adjusted HR 2.04; 95% CI: 1.68 to 2.47) after adjustment for IDU. Both IDU and HCV were strongly associated with liver-related mortality (adjusted HR 10.89; 95% CI: 6.47 to 18.3 for IDU and adjusted HR 14.0; 95% CI: 8.05 to 24.5 for HCV) with greater attenuation of the effect of IDU (adjusted HR 2.43; 95% CI: 1.24 to 4.78) than for HCV (adjusted HR 7.97; 95% CI: 3.83 to 16.6). Rates of CNS, respiratory and violent deaths remained elevated in IDU after adjustment for HCV.
  
  
  CONCLUSIONS
  A substantial proportion of the excess mortality in HIV-infected IDU is explained by HCV coinfection. These findings underscore the potential impact on mortality of new treatments for HCV in HIV-infected people.
authors.affiliation: *School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom; †Schools of Medicine and Public Health, Yale University, New Haven, CT; ‡VA Connecticut Healthcare System, West Haven, CT; §Stichting HIV Monitoring, Amsterdam, the Netherlands; ‖Research Department of Infection and Population Health, University College London, London, United Kingdom; ¶Fédération des Maladies Infectieuses, Centre Hospitalo-Universitaire Pellegrin, Bordeaux, France; #INSERM U943 and UPMC UMR-S-943, Paris, France; **Department of Internal Medicine, University Hospital Bonn, Bonn, Germany; ††Department of Infectious Diseases, Ramón y Cajal Hospital, IRYCIS, Madrid, Spain; ‡‡Atlanta Veterans Affairs Medical Center, Decatur, GA; §§Clinic of Infectious Diseases and Tropical Medicine, San Paolo Hospital, University of Milan, Milan, Italy; ‖‖Fundació de la Lluita contra la Sida, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain; ¶¶Division of Infectious Diseases, University of Calgary, Calgary, Alberta, Canada; ##Department of Infectious Diseases, Cantonal Hospital St. Gallen, Gallen, Switzerland; ***CHIP, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; †††Division of Infectious Disease, Department of Medicine, University of Alabama, Birmingham, AL; ‡‡‡Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, TN; and §§§Division of Allergy and Infectious Diseases, University of Washington School of Medicine, Seattle, WA.
authors.forename: Margaret T
authors.initials: MT
authors.lastname: May
authors.forename: Amy C
authors.initials: AC
authors.lastname: Justice
authors.forename: Kate
authors.initials: K
authors.lastname: Birnie
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Ingle
authors.forename: Colette
authors.initials: C
authors.lastname: Smit
authors.forename: Colette
authors.initials: C
authors.lastname: Smith
authors.forename: Didier
authors.initials: D
authors.lastname: Neau
authors.forename: Marguerite
authors.initials: M
authors.lastname: Guiguet
authors.forename: Carolynne
authors.initials: C
authors.lastname: Schwarze-Zander
authors.forename: Santiago
authors.initials: S
authors.lastname: Moreno
authors.forename: Jodie L
authors.initials: JL
authors.lastname: Guest
authors.forename: Antonella dʼArminio
authors.initials: Ad
authors.lastname: Monforte
authors.forename: Cristina
authors.initials: C
authors.lastname: Tural
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Gill
authors.forename: Andrea
authors.initials: A
authors.lastname: Bregenzer
authors.forename: Ole
authors.initials: O
authors.lastname: Kirk
authors.forename: Michael
authors.initials: M
authors.lastname: Saag
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Sterling
authors.forename: Heidi M
authors.initials: HM
authors.lastname: Crane
authors.forename: Jonathan A C
authors.initials: JA
authors.lastname: Sterne
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000401:mortality*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D015819:Substance Abuse, Intravenous / Q000150:complications*; D016019:Survival Analysis; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents
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