Frequency and mutation patterns of resistance in patients with chronic hepatitis B infection treated with nucleos(t)ide analogs in add-on and switch strategies.
Introduction: Two patterns of ETV resistance have been characterized, and they include the LAM-resistance mutation rtM204I/V plus an additional mutation of either rtT184G + rtS202I/C or rtM250V + rtI169T .
Th1 and Th2 immune response in chronic hepatitis B patients during a long-term treatment with adefovir dipivoxil.
Method: In brief, serum HBV DNA was amplified by PCR and pyrosequenced to detect the following mutations of HBV polymerase: I169T
Result: The serum samples of these two patients were examined for ten HBV mutations (I169T, V173L, L180M, A181V/T, T184G/S/A/C, A194T, S202G/I, M204V/I, N236T, M250V) that have been reported in the reverse transcriptase regions of HBV polymerase gene in association with the HBV resistance to the treatment of nucleoside and nucleotide analogs.
[Detection of HBV resistant mutations related to lamivudine, adefovir and entecavir by reverse hybridization technique].
Abstract: RESULTS: The specific probes of 10 codon positions related to HBV wild-type and resistant reference strains, including I169T, V173L, L180M, A181T, T184G, S202I, M204V, Q215S, N236T, M250V, were distinguished effectively by reverse hybridization method.
Abstract: To detect non-synonymous amino acid substitutions associated with lamivudine, adefovir and entecavir, 26 specific oligonucleotide probes covering ten different codon positions, I169T, V173L/G, L180M, A181T/V, PMID: 20380793
2010
Zhonghua gan zang bing za zhi
Abstract: The overall incidence rate of A181V/T mutation in genotype C (5.3%) was significantly higher than that in genotype B (0.4%) (x2=12.23, P less than 0.01), but the incidence rate of M204I/V, L180M, T184A/G/I/S, S202G/I and V173L mutations was not significantly different between genotype B and C (each P more than 0.05).
Mechanistic characterization and molecular modeling of hepatitis B virus polymerase resistance to entecavir.
Result: Several different ETVr substitutions have been observed in ETV-treated patients, including T184A/C/F/G/I/L/M/S, S202C/G/I, and M250 I/L/V.
Result: The only exception was the most resistant, quadruple-substituted RT with ETVr T184G+S202I changes in a M204V+L180M LVDr background, where the apparent Km for dGTP was approximately 7-fold less than that for wildtype.
Result: The smaller T184G substitution (relative to threonine) allows the YMDD loop to be more flexible which dynamically closes the ETV binding pocket.
Ultra-deep pyrosequencing of hepatitis B virus quasispecies from nucleoside and nucleotide reverse-transcriptase inhibitor (NRTI)-treated patients and NRTI-naive patients.
PMID: 19301976
2009
The Journal of infectious diseases
Method: Established NRTI-resistance mutations included the following RT mutations: rtL80V/I, rtI169T, rtV173L, rtL180M, rtA181TV, rtT184S/A/I/L/F/G, rtA194T, rtS202G/I, rtM204V/I/S, rtN236T, and rt PMID: 19669299
2008
Hepatology international
Abstract: Both pathways are associated with clusters of secondary mutations that can affect subsequent treatment with NAs (rtT184G, rtS202I) such as ETV.
Hepatitis B virus polymerase variants associated with entecavir drug resistance in treatment-naive patients.
Abstract: The aim of this study was to determine the prevalence of HBV variants associated with ETV resistance (rtI169T, rtT184G, rtS202I, rtM250V) in naive patients before and during lamivudine therapy.
Clinical emergence of entecavir-resistant hepatitis B virus requires additional substitutions in virus already resistant to Lamivudine.
PMID: 15328117
2004
Antimicrobial agents and chemotherapy
Abstract: Reduced susceptibility in vitro was highest when both the rtT184G and the rtS202I changes were combined with the 3TC(r) substitutions.
Abstract: Viral rebound occurred after 76 weeks of therapy with ETV at 1.0 mg, with the emergence of rtT184G, rtI169T, and rtS202I substitutions within the preexisting 3TC(r) background.