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Entecavir (Baraclude) Works Well in Patients with Adefovir-resistant Hepatitis B, but Lamivudine Resistance Compromises Efficacy

SUMMARY: The nucleoside analog entecavir (Baraclude) worked well in previously untreated chronic hepatitis B patients and in people who had developed resistance to the nucleotide analog adefovir (Hepsera), but did not perform well in people with resistance to lamivudine (Epivir-HBV) according to a European study described in the April 2010 Journal of Hepatology. Among patients who developed resistance to entecavir, tenofovir (Viread) remained an effective option.

By Liz Highleyman

Several 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).


Among the 104 nucleoside/nucleotide-naive participants 79% achieved virological response (HBV DNA < 80 IU/mL).
None of these patients developed entecavir-resistant virus, according to genotypic testing.
Among the 57 nucleoside/nucleotide-experienced patients, 54% achieved virological response.
Patients 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).
Antiviral efficacy did not decrease significantly, however, among lamivudine treated participants who did not develop lamivudine-resistance mutations (HR 0.81; P = 0.52).
Prior use of adefovir did not compromise virological response to entecavir, whether or not adefovir resistance mutations emerged (HR 0.84 and 0.86, respectively).
Among patients who developed entecavir resistance mutations, switching to a tenofovir-containing regimen led to virological response.

"Entecavir 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," they added.

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, Germany.


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). April 2010.























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FDA-approved Therapies for Chronic HBV Infection
Baraclude  (entecavir)
  (lamivudine; 3TC)
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Intron A  (interferon alfa-2b)
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