Despite increasing use of antiretrovirals, no reduction in end-stage liver disease risk was observed among patients coinfected with HIV and viral hepatitis during a 15-year period, according to an analysis of data from The North American AIDS Cohort Collaboration on Research and Design.
“Patients triply infected with HIV, hepatitis C virus and hepatitis B virus were at particularly high risk, having a 12-fold higher incidence rate of [end-stage liver disease (ESLD)] compared with HIV monoinfected patients, even in the modern ART era,” Marina B. Klein, MD, MSc, FRCPC, professor in the division of infectious diseases at McGill University, and colleagues wrote. “Even after accounting for competing risks of death, CD4 and HIV RNA suppression, we observed no apparent improvement in ESLD rates in our HIV/HCV coinfected population.”
Although patients with HIV who are coinfected with HBV or HCV are at increased risk for ESLD, whether use of modern ART reduced that risk was unknown.
Thus, Klein and colleagues sought to estimate trends in ESLD among patients with HIV, with and without HBV and HCV coinfection, during three eras corresponding to major changes in ART availability, safety and clinical practice: early (1996-2000), middle (2001-2005) and modern (2006-2010).
Klein and colleagues evaluated data on individuals with HIV from 12 clinical cohorts in the United States and Canada participating in the North American AIDS Cohort Collaboration on Research and Design that validated ESLD events from 1996 through 2010. ESLD incidence rates and rate ratios, based on hepatitis status, were adjusted for age, sex, race, cohort and time-updated CD4 cell count and HIV RNA.
Among the 34,119 patients who met inclusion criteria, 380 incidents of ESLD occurred during 129,818 person-years of follow-up.
The incidence of ESLD was highest in patients triply infected by HIV, HBV and HCV (11.57 per 1,000 person-years), compared with patients coinfected with HBV (8.72 per 1,000 person-years), patients coinfected with HCV (6.1 per 1,000 person-years) and patients monoinfected with HIV (1.27 per 1,000 person-years).
The researchers calculated the adjusted IRR to compare the incidence of ESLD in the modern vs. early ART eras for patients with HCV (adjusted IRR = 0.95; 95% CI, 0.61-1.47), HBV (aIRR = 0.95; 95% CI, 0.4-2.26) and triply infected patients (aIRR = 1.52; 95% CI, 0.46-5.02).
“There was no evidence that ESLD event rates changed appreciably over time, nor among any category of hepatitis infection, except possibly for a decrease in ESLD incidence among those infected with HBV in the modern ART era compared to earlier eras,” the researchers wrote. “There was no evidence that ART era modified the effect of viral coinfection status on ESLD incidence.”
Klein and colleagues noted that independent treatments for HCV and HBV exist and are underutilized. They found that, in the modern era, 35% of patients with HBV were not receiving Viread (tenofovir disoproxil fumarate, Gilead Sciences), and there was little use of HCV therapy.
“The continued high incidence of ESLD despite modern ART underscores the urgent need to specifically address HCV and HBV infections in HIV infected adults,” they concluded. “Improved identification, staging, monitoring and treatment of coinfected persons should be prioritized.”
In a related editorial, Linda Wittkop, MD, PhD, associate professor of epidemiology and biostatistics at the University of Bordeaux, noted that powerful treatments for HBV exist and that, with the introduction of direct-acting antivirals, HCV has become a modifiable risk factor.
“Thus, future studies will need to assess the effect of a broader use of DAAs in HCV/HIV coinfected patients on the risk of end-stage liver disease,” she wrote. “Specific cohorts … or cohort collaborations with long-term follow-up are needed to enable comprehensive analysis to better understand liver and nonliver related disease progression and its factors associated in both HCV and HBV coinfected patients.” – by Sarah Kennedy
Disclosures: Klein reports research support from Merck and ViiV Healthcare, and consulting fees from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Merck and ViiV Healthcare. Please see the full study for a list of all other authors’ relevant financial disclosures. Wittkop reports no relevant financial disclosures.