Evolution of hepatitis B virus polymerase gene sequence during famciclovir therapy for chronic hepatitis B

B Seignères, C Pichoud, SS Ahmed… - The Journal of …, 2000 - academic.oup.com
B Seignères, C Pichoud, SS Ahmed, O Hantz, C Trépo, F Zoulim
The Journal of infectious diseases, 2000academic.oup.com
Prolonged administration of nucleoside analogues for chronic hepatitis B may result in the
emergence of hepatitis B viral polymerase mutants. To gain insight into the mechanism
involved in the virus's resistance to famciclovir, the amino acid sequences of the terminal
protein and reverse-transcriptase (RT) domains of the viral polymerase were determined
during therapy among 28 patients. The antiviral response was independent of viral
genotypes, and non-response to famciclovir was associated with a complex variability of the …
Abstract
Prolonged administration of nucleoside analogues for chronic hepatitis B may result in the emergence of hepatitis B viral polymerase mutants. To gain insight into the mechanism involved in the virus's resistance to famciclovir, the amino acid sequences of the terminal protein and reverse-transcriptase (RT) domains of the viral polymerase were determined during therapy among 28 patients. The antiviral response was independent of viral genotypes, and non-response to famciclovir was associated with a complex variability of the RT domain. No mutation in the YMDD motif was observed, whereas an L528M mutation was clearly selected by famciclovir treatment in 2 patients, as well as 14 novel mutations in 7 patients. Clone sequence analysis of the RT domains of patients undergoing retreatment with famciclovir and/or lamivudine showed the selection of a preexisting drug-resistant mutant in one case and indicated that sequential antiviral therapy may allow the rapid selection of resistant strains.
Oxford University Press