BACKGROUND/AIMS: The susceptibility of adefovir-resistant hepatitis B virus (HBV) mutants is only reduced by 3-10-fold in in vitro studies, suggesting that virologic breakthrough and clinical deterioration are unlikely. The aim of this study was to describe the clinical course of patients with adefovir-resistant HBV infection. METHODS: Testing for adefovir-resistant mutations was performed on patients who had a suboptimal response or virologic breakthrough on adefovir. Adefovir-resistant mutations were detected using a line probe assay and direct sequencing of the HBV P-gene. RESULTS: Eight male patients with pre-existing lamivudine resistance or breakthrough (mean age 47+/-13 years) were found to have adefovir-resistant mutations rtA181V/T or rtN236T. Baseline median ALT was 66 IU/L (range, 27-1161) and median HBV DNA 7.9 log10 copies/ml (range, 6-8.3). At the time of adefovir resistance (mean of 20+/-9 months), HBV DNA increased to > or = 5 log10 copies/ml in 7 patients. After detection of adefovir resistance, hepatic decompensation occurred in 2 patients, 1 of whom died. Salvage therapy with lamivudine, entecavir or tenofovir was given to 7 patients and a reduction in HBV DNA by > or = 3 log10 was seen in 3 patients. CONCLUSIONS: In conclusion, adefovir resistance can be associated with significant viral rebound and hepatic decompensation which may be fatal.
BACKGROUND/AIMS: The susceptibility of adefovir-resistant hepatitis B virus (HBV) mutants is only reduced by 3-10-fold in in vitro studies, suggesting that virologic breakthrough and clinical deterioration are unlikely. The aim of this study was to describe the clinical course of patients with adefovir-resistant HBV infection. METHODS: Testing for adefovir-resistant mutations was performed on patients who had a suboptimal response or virologic breakthrough on adefovir. Adefovir-resistant mutations were detected using a line probe assay and direct sequencing of the HBV P-gene. RESULTS: Eight male patients with pre-existing lamivudine resistance or breakthrough (mean age 47+/-13 years) were found to have adefovir-resistant mutations rtA181V/T or rtN236T. Baseline median ALT was 66 IU/L (range, 27-1161) and median HBV DNA 7.9 log10 copies/ml (range, 6-8.3). At the time of adefovir resistance (mean of 20+/-9 months), HBV DNA increased to > or = 5 log10 copies/ml in 7 patients. After detection of adefovir resistance, hepatic decompensation occurred in 2 patients, 1 of whom died. Salvage therapy with lamivudine, entecavir or tenofovir was given to 7patients and a reduction in HBV DNA by > or = 3 log10 was seen in 3 patients. CONCLUSIONS: In conclusion, adefovir resistance can be associated with significant viral rebound and hepatic decompensation which may be fatal.
Authors: Daniel J Tenney; Ronald E Rose; Carl J Baldick; Steven M Levine; Kevin A Pokornowski; Ann W Walsh; Jie Fang; Cheng-Fang Yu; Sharon Zhang; Charles E Mazzucco; Betsy Eggers; Mayla Hsu; Mary Jane Plym; Patricia Poundstone; Joanna Yang; Richard J Colonno Journal: Antimicrob Agents Chemother Date: 2006-12-18 Impact factor: 5.191