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American Association For The Study of Liver Diseases
November 11-15, 2005 San Francisco
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Low Rate of Viral Rebound Seen in HBV Patients Treated With Entecavir
  Rabiya S. Tuma, PhD
Nov. 15, 2005 (San Francisco) - Extended treat ment for hepatitis B virus (HBV) infection with the nucleoside analog entecavir appears effective, even in patients who are resistant to lamivudine, according to a study presented here at the 56th annual meeting of the American Association for the Study of Liver Diseases.
To determine the long-term resistance rates of patients treated with entecavir, Richard Colonno, PhD, vice president of infectious diseases drug discovery at Bristol-Myers Squibb, and colleagues analyzed two-year outcomes data from five different clinical trials. None of the 679 patients who were nucleoside-naive (participants from trials 022/901 and 027/901) showed resistance after year 1, nor did the 310 of those patients who continued on therapy for a second year. However, 11 patients showed evidence of viral rebound, defined as one log or greater increase in viral load based on polymerase chain reaction (PCR) assays, during the first year and another seven did so in the second year.
Of 192 patients refractory to lamivudine (participants from trials 014/901, 015/901, and 026/901), two (1%) became resistant to entecavir during the first year, and five more showed evidence of viral rebound. Of the 154 lamivudine-refractory patients treated for a second year with entecavir, 14 (9%) developed resistance and an additional 20 experienced viral rebound.
Sequence data of virus isolated from the 16 phenotypically resistant patients indicated that all of the emerging viral strains carried multiple mutations known to induce lamivudine resistance, as well as substitutions at two additional amino acid residues, T184 and S202.
Because none of the nucleoside-naive patients developed resistance, the team concluded that there was "no evidence that lamivudine resistant substitutions are selected on entecavir therapy."
"The real message with this drug is its potency," Dr. Colonno told Medscape. "The drug reduces viral load very quickly." With fewer virus available to undergo replication and mutation, the likelihood of developing resistance drops significantly.
Of the nucleoside-naive patients included in the study, 93% had fewer than 300 copies/mL of HBV DNA by 96 weeks of therapy. This included 81% of the 352 patients who were HBeAg positive at the start of the trial. Based on PCR analysis, the number of DNA copies continues to decrease in patients previously treated with lamivudine, with 30% achieving HBV DNA levels below 300 copies/mL at 96 weeks.
Dr. Colonna and coauthors on this study are employees of Bristol-Myers Squibb, which manufactures entecavir. This study and the studies in which the patients were initially treated were funded by Bristol-Myers Squibb.
AASLD 56th Annual Meeting: Abstract 962. Presented on Nov. 13, 2005.
Reviewed by Maria L. Gaiso, PhD