Some Individuals Harbor HBV with Adefovir (Hepsera) and Tenofovir (Viread) Resistance Mutations before They Ever Receive Treatment

By Liz Highleyman

Several nucleoside/nucleotide drugs have potent activity against hepatitis B virus (HBV), but the virus can rapidly develop resistance, presenting a barrier to long-term treatment success.

While it is well known that the rapid, error-prone replication of HBV can promote emergence of drug resistance mutations in patients undergoing therapy (especially monotherapy with a single agent), such mutations may also be present in people who have never before received treatment, according to a report in the February 14, 2009 World Journal of Gastroenterology.

The French investigators described 2 chronic hepatitis B patients who received HBV polymerase gene sequencing. Although they had never been treated, both had mutations in the viral polymerase associated with resistance to adefovir (Hepsera) and tenofovir (Viread). One patients had mutations rtV214A/rtN238T, while the other had rtA194T.

"[M]utations in untreated patients deserve cautious surveillance," the study authors concluded. "These data indicate that mutations that can theoretically confer adefovir or tenofovir resistance may emerge in treatment-naive patients."

This report suggests that, as is the case with HIV, treatment-naive hepatitis B patients may have primary or pre-existing resistance -- possibly due to random mutations in the wild-type virus or transmission of resistant viral strains from a treated person -- thus adding support for combination first-line therapy.

Institut de Virologie, 3 Rue Koeberle, 67000 Strasbourg, France.

4/17/09

Reference
R Pastor, F Habersetzer, S Fafi-Kremer, and others. Hepatitis B virus mutations potentially conferring adefovir/tenofovir resistance in treatment-naive patients. World Journal of Gastroenterology 15(6): 753-755. February 14, 2009. (Asbtract).