(Baraclude) Works Well in Patients with Adefovir-resistant Hepatitis
B, but Lamivudine Resistance Compromises Efficacy
nucleoside and nucleotide analog drugs are effective against
hepatitis B virus (HBV), but
when they are used alone the virus can quickly develop resistance,
thereby compromising long-term treatment success.
Jurrien Reijnders and fellow investigators with the VIRGIL Surveillance
Study Group evaluated initial or sequential monotherapy using
entecavir in 161 chronic B patients, 34% of whom had received
previous nucleoside/nucleotide treatment. Participants were
followed for a median of about 1 year (range 3-31 months).
the 104 nucleoside/nucleotide-naive participants 79% achieved
virological response (HBV DNA < 80 IU/mL).
of these patients developed entecavir-resistant virus, according
to genotypic testing.
the 57 nucleoside/nucleotide-experienced patients, 54% achieved
who had HBV mutations conferring lamivudine resistance at
the start of entecavir monotherapy had a significantly reduced
probability of achieving virological response compared with
lamivudine-naive patients (hazard ratio [HR] 0.14, or a
86% reduction; P = 0.007).
efficacy did not decrease significantly, however, among
lamivudine treated participants who did not develop lamivudine-resistance
mutations (HR 0.81; P = 0.52).
use of adefovir did not compromise virological response
to entecavir, whether or not adefovir resistance mutations
emerged (HR 0.84 and 0.86, respectively).
patients who developed entecavir resistance mutations, switching
to a tenofovir-containing regimen led to virological response.
proved to be efficacious in [nucleoside/nucleotide]-naive patients,"
the study authors concluded. "The antiviral efficacy of
entecavir was not influenced by prior treatment with adefovir
or presence of adefovir resistance."
"Entecavir should not be used in patients with previous
lamivudine resistance, yet it may still be an option in lamivudine-experienced
patients in case lamivudine resistance never developed,"
These findings indicate that people who develop resistance to
one nucleoside/nucleotide analog have a good chance of responding
to some other agents in the class, at least in the short term.
But the standard of care for chronic hepatitis B is shifting
toward initial combination therapy, which can slow or prevent
emergence of resistance over the long term.
Erasmus MC, University Medical Center Rotterdam, Rotterdam,
Netherlands; Medical School Hannover, Hannover, Germany; University
of Hamburg, Hamburg, Germany; Hotel Dieu Hospital Lyon, Lyon,
France; Clinic of Infectious Diseases, University of Foggia,
Foggia, Italy; Hospital Vall de Hebron, and Ciber-EHD, Barcelona,
Spain; Charité University Medical Center Berlin, Berlin,
JG Reijnders, K Deterding, J Petersen, and others (VIRGIL Surveillance
Study Group). Antiviral effect of entecavir in chronic hepatitis
B: influence of prior exposure to nucleos(t)ide analogues. Journal
of Hepatology 52(4): 493-500 (Abstract).