Kinetics of HBV mutants conferring adefovir resistance (rtn236t) and a method to detect them rapidly / 中华肝脏病杂志
Chinese Journal of Hepatology
; (12): 33-37, 2008.
Article
in Zh
| WPRIM
| ID: wpr-277615
Responsible library:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>The aim was to build a PCR-RFLP method for detecting rtN236T mutants and to observe their kinetics in chronic hepatitis B (CHB) patients.</p><p><b>METHODS</b>Seven CHB patients who had suboptimal viral response or viral breakthrough under adefovir mono-therapy were studied. Part of the HBV reverse transcriptional gene from serial sera samples was sequenced with PCR products or cloned HBV DNA; mutations at rt236 were simultaneously analyzed by a PCR-RFLP assay. Genetic diversity of HBV was observed by calculating Hamming distance within domains B, C and D of RT.</p><p><b>RESULTS</b>Three patients had viral breakthrough and one with suboptimal viral response had adefovir-resistance mutants, one had rtA181V mutation and three had rtN236T mutation. A novel PCR-RFLP assay based on restriction enzyme HpaI or DraI for on the detection of rtN236T mutant was established, which detected 10% minor strains with 100% specificity. Mutants (rtA181V or rtN236T) appeared 0-8 months earlier than the viral breakthrough, then afterwards became the dominant ones. In one patient after stopping the adefovir therapy, 3 months later a wild type virus re-took again the mutant one (rtN236T); in one patient who developed a rt236T mutant after 132 weeks of adefovir treatment, a novel mutant (rtN236V) appeared and then became the dominant one while adefovir treatment continued.</p><p><b>CONCLUSIONS</b>A rapid and easy method was established to detect rtN236T mutants. Mutants for adefovir-resistance accumulated rapidly then became dominant, but they could be taken over again by a wild type or novel mutant HBV.</p>
Full text:
1
Index:
WPRIM
Main subject:
Antiviral Agents
/
Pharmacology
/
Virology
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Polymorphism, Restriction Fragment Length
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DNA, Viral
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Adenine
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Hepatitis B virus
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Polymerase Chain Reaction
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Drug Resistance, Viral
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Organophosphonates
Limits:
Adult
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Humans
/
Male
Language:
Zh
Journal:
Chinese Journal of Hepatology
Year:
2008
Type:
Article