Detection of hepatitis B virus variants resistant to lamivudine and famciclovir among randomly selected chronic carriers from Spain.
BACKGROUND
Treatment for chronic hepatitis B with lamivudine is often hampered by the emergence of point mutations in the YMDD motif of the HBV DNA polymerase gene that confer drug resistance. This usually occurs after several months of therapy, but early detection of lamivudine-resistant mutants has been reported among patients in South Korea. Data from Japan and France suggest that naturally occurring, lamivudine-resistant hepatitis B virus (HBV) variants can be found among chronic carriers who have never received lamivudine treatment. Famciclovir can be used as an alternative when lamivudine-resistant variants emerge, though the substitute treatment may also give rise to the emergence and selection of drug-resistant variants.


METHODS
The presence of mutations related with lamivudine and famciclovir resistance was studied in serum samples from 79 randomly selected Spanish HBV carriers, using a line probe assay (LiPA) on HBV genome fragments amplified by polymerase chain reaction. Data concerning antiviral therapy prior to sampling were available for these patients.


RESULTS
Mutations related with resistance to either drug were detected in ten patients. Three of them (3.8% of the 79 carriers studied) had no record of prior lamivudine or famciclovir treatment at the time of sampling. Wild-type strains together with either the rtM204I (M552I) or rtV207I (V555I) point mutation were found in two of these cases, and the rtV207I mutation alone was detected in the third.


CONCLUSIONS
These findings seem to indicate that lamivudine and famciclovir-resistant variants circulate among Spanish HBV carriers. Since it is expected that antiviral therapy will be ineffective when drug-resistant variants are present before the beginning of treatment, it could be beneficial to test for these variants as an additional routine procedure when designing antiviral therapy on an individual basis.
León
Pilar
P
Diagnostic Microbiology Department, National Center for Microbiology. Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Pozo
Francisco
F
Echevarría
José M
JM
D015075:2-Aminopurine / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000235:genetics; D003955:Diagnostic Tests, Routine; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D000077595:Famciclovir; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology* / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D017354:Point Mutation; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D012189:Retrospective Studies; D013030:Spain / Q000453:epidemiology
D000998:Antiviral Agents; D004279:DNA, Viral; D019259:Lamivudine; D015075:2-Aminopurine; D012194:RNA-Directed DNA Polymerase; D000077595:Famciclovir