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      Risk of End-Stage Liver Disease in HIV-Viral Hepatitis Coinfected Persons in North America From the Early to Modern Antiretroviral Therapy Eras

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      Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
      Oxford University Press
      HIV, hepatitis C virus, hepatitis B virus, coinfection, end-stage liver disease

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          Abstract

          Despite increasing use of antiretrovirals, no clear reduction in end-stage liver disease events was observed in American human immunodeficiency virus–viral hepatitis–coinfected patients over 15 years. Direct-acting antivirals for hepatitis C and tenofovir-based regimens for hepatitis B should be prioritized.

          Abstract

          Background.  Human immunodeficiency virus (HIV)–infected patients coinfected with hepatitis B (HBV) and C (HCV) viruses are at increased risk of end-stage liver disease (ESLD). Whether modern antiretroviral therapy has reduced ESLD risk is unknown.

          Methods.  Twelve clinical cohorts in the United States and Canada participating in the North American AIDS Cohort Collaboration on Research and Design validated ESLD events from 1996 to 2010. ESLD incidence rates and rate ratios according to hepatitis status adjusted for age, sex, race, cohort, time-updated CD4 cell count and HIV RNA were estimated in calendar periods corresponding to major changes in antiretroviral therapy: early (1996–2000), middle (2001–2005), and modern (2006–2010) eras.

          Results.  Among 34 119 HIV-infected adults followed for 129 818 person-years, 380 incident ESLD outcomes occurred. ESLD incidence (per 1000 person-years) was highest in triply infected (11.57) followed by HBV- (8.72) and HCV- (6.10) coinfected vs 1.27 in HIV-monoinfected patients. Adjusted incidence rate ratios (95% confidence intervals) comparing the modern to the early antiretroviral era were 0.95 (.61–1.47) for HCV, 0.95 (.40–2.26) for HBV, and 1.52 (.46–5.02) for triply infected patients. Use of antiretrovirals dually activity against HBV increased over time. However, in the modern era, 35% of HBV-coinfected patients were not receiving tenofovir. There was little use of HCV therapy.

          Conclusions.  Despite increasing use of antiretrovirals, no clear reduction in ESLD risk was observed over 15 years. Treatment with direct-acting antivirals for HCV and wider use of tenofovir-based regimens for HBV should be prioritized for coinfected patients.

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          Author and article information

          Journal
          Clin Infect Dis
          Clin. Infect. Dis
          cid
          cid
          Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
          Oxford University Press
          1058-4838
          1537-6591
          01 November 2016
          09 August 2016
          01 November 2017
          : 63
          : 9
          : 1160-1167
          Affiliations
          [1 ] McGill University Health Centre , Montreal, Quebec, Canada
          [2 ] Johns Hopkins University , Baltimore, Maryland
          [3 ] University of Washington , Seattle
          [4 ] University of Pennsylvania , Philadelphia
          [5 ] British Columbia Centre for Excellence in HIV/AIDS and University of British Columbia , Vancouver, Canada
          [6 ] Kaiser Permanente Northern California , Oakland
          [7 ] Vanderbilt University , Nashville, Tennessee
          [8 ] Northern Ontario School of Medicine , Sudbury, Canada
          [9 ] University of North Carolina , Chapel Hill
          [10 ] University of Calgary , Alberta, Canada
          [11 ] Yale University and the Veterans Affairs Connecticut Healthcare System , New Haven
          [12 ] University of California at San Francisco , California
          [13 ] National Cancer Institute, National Institutes of Health , Bethesda, Maryland
          [14 ] Retrovirus Research Center, Universidad Central del Caribe , Bayamon, Puerto Rico
          [15 ] University of California at San Diego , La Jolla
          Author notes
          Correspondence: M. B. Klein, Chronic Viral Illness Service, McGill University Health-Glen Site, 1001 Decarie Boulevard, D02.4110, Montreal, QC, Canada, H4A 3J1 ( marina.klein@ 123456mcgill.ca ).
          Article
          PMC5064164 PMC5064164 5064164 ciw531
          10.1093/cid/ciw531
          5064164
          27506682
          2c97bea2-8669-4ac0-83cc-7a7e7eb69204
          © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com
          History
          : 16 February 2016
          : 30 June 2016
          Funding
          Award ID: U01-AI069918, U01-AA013566, U01-AA020790, U01-AI31834, U01-AI34989, U01-AI34993, U01-AI34994, U01-AI35004, U01-AI35039, U01-AI35040, U01-AI35041, U01-AI35042, UM1-AI35043, U01-AI37613, U01-AI37984, U01-AI38855, U01-AI38858, U01-AI42590, U01-AI68634, U01-AI68636, U01-AI69432, U01-AI69434, U01-DA036935, U01-HD32632, U10-EY08052, U10-EY08057, U10-EY08067, U24-AA020794, U54-MD007587, UL1-RR024131, UL1-TR000083, F31-DA037788, G12- MD007583, K01-AI071754, K01-AI093197, K23-EY013707, K24-DA00432, K24-AI065298, KL2-TR000421, MO1-RR-00052, N02-CP55504, P30-AI027763, P30-AI094189, P30-AI27757, P30-AI27767, P30-AI036219, P30-AI50410, P30-AI54999, P30-MH62246, R01-AA16893, R01-CA165937, U01-DA036297, K24-AI118591, R01-DA11602, R01-DA12568, R24-AI067039, R56-AI102622, Z01-CP010214, and Z01-CP010176
          Funded by: National Institutes of Health;
          Award ID: CDC200-2006-18797
          Funded by: Centers for Disease Control and Prevention;
          Award ID: 90047713
          Funded by: Agency for Healthcare Research and Quality;
          Award ID: 90051652
          Funded by: Health Resources and Services Administration;
          Award ID: TGF-96118
          Award ID: HCP-97105
          Award ID: CBR-86906
          Award ID: CBR-94036
          Funded by: Canadian Institutes of Health Research, Canada; Canadian Institutes of Health Research (CIHR) New Investigator;
          Funded by: National Cancer Institute;
          Funded by: National Institutes of Health;
          Categories
          Articles and Commentaries

          end-stage liver disease,HIV,hepatitis C virus,hepatitis B virus,coinfection

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