Background: HIV-infected adults are commonly coinfected with hepatitis B (HBV) and C (HCV) viruses and thus at risk for Endstage Liver Disease (ESLD). Whether safer, more effective modern ART has reduced ESLD rates is unknown. We estimated ESLD incidence since the introduction of combination ART by HBV and HCV co-infection status in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).
Methods: HIV-infected adults participating in the 12 cohorts contributing to the NA-ACCORD who were observed for validated ESLD diagnoses from Jan 1, 1996 to Jan 1, 2010 were included. HBV was defined by a positive surface or e antigen test or detectable HBV DNA. HCV was defined as a positive antibody test or detectable HCV RNA. ESLD events (ascites, SBP, bleeding varices, encephalopathy, hepatoma) were validated using standardized screening and review protocols. Poisson regression models were used to estimate incidence rates (IR, per 1,000 p-years) and ratios (adjusted for age, sex, race and cohort; aIRR) with 95% confidence intervals ([,]) in the early (1996-2000), middle (2001-2005) and modern (2006-2010) ART eras.
Results: 34,119 adults contributed 380 incident ESLD outcomes and >129,000 person-years. Overall, ESLD incidence was similar in the early, middle and modern ART eras. In all three eras, incidence rates were highest in HIV/HCV/HBV and lowest among HIV monoinfected with HIV/HCV/HBV having the highest aIRRs (see Table). No significant change in rates of ESLD was observed across the 3 time periods for any group. Comparing the early vs. modern eras, aIRR [95% CI] were: 1.6[0.8, 3.4]; 1.3[0.8, 2.1] and 0.5 [0.1, 1.9] for HIV/HCV, HIV/HBV and HIV/HCV/HBV respectively. Similarly, comparing middle vs. modern eras, aIRR [95% CI] were: 1.1[0.7, 1.6], 0.8[0.6, 1.2] and 0.5[0.2, 1.2]. Overall death rates were high in the early ART era which may have lead to an underestimation of ESLD risk in this period. However, death rates were similar in the middle and modern eras.
Conclusions: Hepatitis virus co-infected adults are at markedly increased risk for ESLD compared those infected with HIV alone, with triply infected patients at greatest risk. No clear reduction in ESLD risk was observed over the three time periods. The continued high incidence of ESLD despite modern ART underscores the urgent need to specifically address HCV and HBV infections in HIV infected adults.
Table. Incidence of ESLD by ART Era and Hepatitis Status in the NA-ACCORD