Resistance to Adefovir (Hepsera) Is Uncommon after 3 Years in Hepatitis B Patients Treated with Adefovir plus Lamivudine (Epivir-HBV)

Development of drug resistance is a barrier to continued successful treatment in patients with chronic hepatitis B, especially when nucleoside analog antiviral agents are used as monotherapy.

Adefovir (Hepsera) monotherapy is an established treatment for lamivudine (Epivir-HBV)-experienced patients with chronic hepatitis B, but it carries a significant risk of resistance over the long term.

As reported in the November 2007 issue of Gastroenterology, Italian researchers assessed whether the emergence of drug resistance mutations could be overcome by adefovir/lamivudine combination therapy.

A total of 145 chronic hepatitis B patients with lamivudine-resistant HBV were treated with 10 mg adefovir plus 100 mg lamivudine. At baseline, 86% were hepatitis B “e” antigen (HBeAg) negative, 92% had HBV genotype D, and 73% had liver cirrhosis. Liver function tests and HBV DNA levels were assessed bimonthly. Adefovir-related mutations were assessed by INNO-LiPA assay at baseline and at 1-year intervals.

Results

• Over 42 months of follow-up (range 12-74 months), 116 patients (80%) achieved serum HBV DNA clearance.

• 67 subjects (84%) experienced alanine aminotransferase (ALT) normalization.

• All 145 (100%) remained free of virological and clinical breakthrough, regardless of the degree of HBV suppression.

• RT A181V/T was the only detected adefovir-related resistance mutation:

o        In 6 patients at baseline (4%; 1 A181V and 5 A181T);

o        In an additional 3 patients during treatment (2%; all A181T).

• In all 9 patients with adefovir resistance mutations, HBV DNA progressively declined during therapy, and reached an undetectable level in 7 (78%).

• The cumulative rates of emergence of new A181T mutations were:

o        1-year: 1%;

o        2-year: 2%;

o        3-year: 4%;

o        4-year: 4%.

• None of the cirrhotic patients experienced clinical decompensation, but 11 (12%) developed hepatocellular carcinoma.

Conclusion

Based on these findings, the authors concluded, “Under prolonged adefovir/lamivudine therapy, patients with lamivudine-resistant hepatitis B were unlikely to develop genotypic resistance to adefovir and had durable prevention of virologic and clinical breakthrough.”

12/11/07

Reference