Risk of End-Stage Liver Disease in HIV-Viral Hepatitis Coinfected Persons in North America From the Early to Modern Antiretroviral Therapy Eras
Authors: Klein Marina B. , Althoff Keri N. , Jing Yuezhou , Lau Bryan , Kitahata Mari , Lo Re Vincent , Kirk Gregory D. , Hull Mark , Kim H. Nina , Sebastiani Giada , Moodie Erica E.M. , Silverberg Michael J. , Sterling Timothy R. , Thorne Jennifer E. , Cescon Angela , Napravnik Sonia , Eron Joe , Gill M. John , Justice Amy , Peters Marion G. , Goedert James J. , Mayor Angel , Thio Chloe L. , Cachay Edward R. , Moore Richard ,   for the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of IeDEA, Kirk Gregory D. , Benson Constance A. , Bosch Ronald J. , Boswell Stephen , Mayer Kenneth H. , Grasso Chris , Hogg Robert S. , Harrigan P. Richard , Montaner Julio S.G. , Cescon Angela , Samji Hasina , Brooks John T. , Buchacz Kate , Gebo Kelly A. , Moore Richard D. , Moore Richard D. , Rodriguez Benigno , Horberg Michael A. , Silverberg Michael J. , Thorne Jennifer E. , Goedert James J. , Jacobsonc Lisa P. , D'Souza Gypsyamber , Klein Marina B. , Rourke Sean B. , Burchell Ann N. , Rachlis Anita R. , Hunter-Mellado Robert F. , Mayor Angel M. , Gill M. John , Deeks Steven G. , Martin Jeffrey N. , Patel Pragna , Brooks John T. , Saag Michael S. , Mugavero Michael J. , Willig James , Eron Joseph J. , Napravnik Sonia , Kitahata Mari M. , Crane Heidi M. , Kim H. Nina , Drozd Daniel R. , Sterling Timothy R. , Haas David , Bebawy Sally , Turner Megan , Justice Amy C. , Dubrow Robert , Fiellin David , Gange Stephen J. , Anastos Kathryn , Moore Richard D. , Saag Michael S. , Gange Stephen J. , Kitahata Mari M. , Althoff Keri N. , McKaig Rosemary G. , Justice Amy C. , Freeman Aimee M. , Moore Richard D. , Freeman Aimee M. , Lent Carol , Kitahata Mari M. , Van Rompaey Stephen E. , Crane Heidi M. , Drozd Daniel R. , Morton Liz , McReynolds Justin , Lober William B. , Gange Stephen J. , Althoff Keri N. , Abraham Alison G. , Lau Bryan , Zhang Jinbing , Jing Jerry , Golub Elizabeth , Modur Shari , Wong Cherise , Hogan Brenna , Tong Weiqun , Liu Bin 
Published: August 2016

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.