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

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.

Keywords: HIV; coinfection; end-stage liver disease; hepatitis B virus; hepatitis C virus.

Figure 1.

End-stage liver disease (ESLD) incidence rates and 95% confidence intervals by viral hepatitis coinfection status and antiretroviral therapy (ART) era, North American AIDS Cohort Collaboration on Research and Design, January 1996–December 2010. Abbreviations: HBV, hepatitis B virus; HCV, hepatitis C virus.

Figure 2.

Human immunodeficiency virus (HIV) RNA suppression by viral hepatitis coinfection status and antiretroviral therapy (ART) era, North American AIDS Cohort Collaboration on Research and Design, January 1996–December 2010. Notes: HIV RNA suppression was defined as <500 copies/mL. Each patient's minimum HIV RNA measurement was selected in the time periods. The denominator for the proportions included all patients under observation during that time period, based on baseline and study exit. Abbreviations: HBV, hepatitis B virus; HCV, hepatitis C virus.

Figure 3.

Prescription of hepatitis B virus (HBV)-active antiretroviral therapies (ART; dark gray bars) overlayed with the proportion prescribed tenofovir among those receiving HBV-active therapy (light gray bars), by viral hepatitis coinfection status and ART era, North American AIDS Cohort Collaboration on Research and Design, January 1996–December 2010. Proportion prescribed HBV-active ART represents the number of those prescribed HBV-active agents (tenofovir [TDF], lamivudine [3TC], and emtricitabine [FTC])/the number of those prescribed ART. The proportion prescribed TDF represents the number of those prescribed TDF/the number of those prescribed HBV-active ART and is additionally displayed as a percentage overlying the bars. Abbreviation: HCV, hepatitis C virus.