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

Marina B. Klein, Keri Althoff, Yuezhou Jing, Bryan M Lau, Mari Kitahata, Vincent Lo Re, Gregory D Kirk, Mark Hull, H. Nina Kim, Giada Sebastiani, Erica E M Moodie, Michael J. Silverberg, Timothy R. Sterling, Jennifer Thorne, Angela Cescon, Sonia Napravnik, Joe Eron, M. John Gill, Amy Justice, Marion G. Peters & 5 others James J. Goedert, Angel Mayor, Chloe L Thio, Edward R. Cachay, Richard D Moore

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1160-1167
Number of pages8
JournalClinical Infectious Diseases
Volume63
Issue number9
DOIs
StatePublished - Nov 1 2016

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End Stage Liver Disease
North America
Hepatitis
HIV
Tenofovir
Therapeutics
Incidence
CD4 Lymphocyte Count
Hepatitis C
Hepatitis B
Canada
Antiviral Agents
Acquired Immunodeficiency Syndrome
Research Design
RNA
Confidence Intervals
Viruses

Keywords

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

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Risk of End-Stage Liver Disease in HIV-Viral Hepatitis Coinfected Persons in North America from the Early to Modern Antiretroviral Therapy Eras. / Klein, Marina B.; Althoff, Keri; Jing, Yuezhou; Lau, Bryan M; 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; 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 D.

In: Clinical Infectious Diseases, Vol. 63, No. 9, 01.11.2016, p. 1160-1167.

Research output: Contribution to journalArticle

Klein, MB, Althoff, K, Jing, Y, Lau, BM, Kitahata, M, Lo Re, V, Kirk, GD, Hull, M, Kim, HN, Sebastiani, G, Moodie, EEM, Silverberg, MJ, Sterling, TR, Thorne, J, Cescon, A, Napravnik, S, Eron, J, Gill, MJ, Justice, A, Peters, MG, Goedert, JJ, Mayor, A, Thio, CL, Cachay, ER & Moore, RD 2016, 'Risk of End-Stage Liver Disease in HIV-Viral Hepatitis Coinfected Persons in North America from the Early to Modern Antiretroviral Therapy Eras', Clinical Infectious Diseases, vol. 63, no. 9, pp. 1160-1167. https://doi.org/10.1093/cid/ciw531
Klein, Marina B. ; Althoff, Keri ; Jing, Yuezhou ; Lau, Bryan M ; 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 ; 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 D. / Risk of End-Stage Liver Disease in HIV-Viral Hepatitis Coinfected Persons in North America from the Early to Modern Antiretroviral Therapy Eras. In: Clinical Infectious Diseases. 2016 ; Vol. 63, No. 9. pp. 1160-1167.
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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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T1 - Risk of End-Stage Liver Disease in HIV-Viral Hepatitis Coinfected Persons in North America from the Early to Modern Antiretroviral Therapy Eras

AU - Klein, Marina B.

AU - Althoff, Keri

AU - Jing, Yuezhou

AU - Lau, Bryan M

AU - Kitahata, Mari

AU - Lo Re, Vincent

AU - Kirk, Gregory D

AU - Hull, Mark

AU - Kim, H. Nina

AU - Sebastiani, Giada

AU - Moodie, Erica E M

AU - Silverberg, Michael J.

AU - Sterling, Timothy R.

AU - Thorne, Jennifer

AU - Cescon, Angela

AU - Napravnik, Sonia

AU - Eron, Joe

AU - Gill, M. John

AU - Justice, Amy

AU - Peters, Marion G.

AU - Goedert, James J.

AU - Mayor, Angel

AU - Thio, Chloe L

AU - Cachay, Edward R.

AU - Moore, Richard D

PY - 2016/11/1

Y1 - 2016/11/1

N2 - 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.

AB - 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.

KW - coinfection

KW - end-stage liver disease

KW - hepatitis B virus

KW - hepatitis C virus

KW - HIV

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