Margaret T May1, Amy C Justice, Kate Birnie, Suzanne M Ingle, Colette Smit, Colette Smith, Didier Neau, Marguerite Guiguet, Carolynne Schwarze-Zander, Santiago Moreno, Jodie L Guest, Antonella dʼArminio Monforte, Cristina Tural, Michael J Gill, Andrea Bregenzer, Ole Kirk, Michael Saag, Timothy R Sterling, Heidi M Crane, Jonathan A C Sterne. 1. *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.
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.
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.
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