aDepartment of Medicine, Division of Infectious Diseases and Chronic Viral Illness Service, McGill University, Montreal, Quebec, CanadabDepartment of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, CanadacDepartment of Medicine, University of British Columbia, Vancouver, British Columbia, CanadadBritish Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, CanadaeUniversity Health Network, University of Toronto, Toronto, Ontario, CanadafCIHR Canadian HIV Trials Network, Vancouver, CanadagSouthern Alberta HIV Clinic, Calgary, CanadahDepartment of Medicine, University of Ottawa, Ottawa, CanadaiDepartment of Microbiology and Infectious Diseases, Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montreal, Quebec, CanadajDivision of Infectious Diseases, Oak Tree Clinic, BC Women's Hospital, Vancouver, Canada.
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Objective:Hepatitis C virus (HCV) treatment may reduce liver-related mortality but with competing risks, other causes of mortality may undermine benefits. We examined changes in cause-specific mortality among HIV-HCV co-infected patients before and after scale-up of HCV treatment.Design:Prospective multicentre HIV-HCV cohort study in Canada.Methods:Cause-specific deaths, classified using a modified “Coding of Cause of Death in HIV” protocol, were determined for two time periods, 2003–2012 and 2013–2017, stratified by age (20–49; 50–80 years). Comparison of trends between periods was performed using Poisson regression. To account for competing risks, multinomial regression was used to estimate the cause-specific hazard ratios of time and age on cause of death, from which ESLD-specific five-year cumulative incidence functions (CIFs) were estimated.Results:Overall, 1634 participants contributed 8248 person-years of follow-up; 273 (17%) died. Drug overdose was the most common cause of death overall, followed by end-stage liver disease (ESLD) and smoking-related deaths. In 2013–2017, ESLD was surpassed by drug overdose and smoking-related deaths among those aged 20–49 and 50–80, respectively. After accounting for competing risks, comparing 2003–2012 to 2013–2017, ESLD deaths declined (adjusted hazards ratio: 0.18, 95% CI 0.05–0.62). However, both early and late period CIFs demonstrated increased risk of death from ESLD for patients with poor HIV control and advanced fibrosis.Conclusions:The gains made in overall mortality with HCV therapy may be thwarted if modifiable harms are not addressed. While ESLD-related deaths have decreased over time, treatment should be further expanded, prioritizing those with advanced fibrosis.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0