Serum lamivudine levels in the presence of a lamivudine-resistant HBV mutant.
OBJECTIVE
Lamivudine efficiently inhibits hepatitis B virus replication and has been used to treat hepatitis B virus recurrence after orthotopic liver transplantation. Although effective, its use is hampered by viral breakthrough due to the appearance of hepatitis B virus drug-resistant strains. Aims of this work were to evaluate the inter- and intra-individual variations of lamivudine serum levels and the effects on the drug levels of the lamivudine-resistant hepatitis B virus mutant infection.


METHODS
Serum lamivudine concentration was measured by high-performance liquid chromatography. Polymerase chain reaction analysis and sequencing analysis of the reverse transcriptase area of the polymerase was performed on each sample using specific primers. A polymerase chain reaction-enzyme-linked immunosorbent assay was used to differentiate between wild-type hepatitis B virus and lamivudine-resistant hepatitis B virus strain.


RESULTS
Lamivudine serum levels presented minor inter- and intra-individual fluctuations along time, with an important increase at the time of the hepatitis flare-up due to the hepatitis B virus mutant presence. When the wild-type hepatitis B virus briefly reappeared as a mixed population, the titre of lamivudine dropped to below the detection level.


CONCLUSIONS
While lamivudine serum levels appears stable when the anti-viral efficacy is fully achieved, important fluctuations are present according to the type of viral population, with a considerable decrease possibly due to the presence of the wild-type virus.
Torre
F
F
Department of Internal Medicine, University of Genoa, Viale Benedetto XV, 6, 16132, Genoa, Italy.
Mattioli
F
F
Campo
N
N
Delfino
A
A
Basso
M
M
Pelli
N
N
Martelli
A
A
Picciotto
A
A
D019380:Anti-HIV Agents / Q000097:blood / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D024882:Drug Resistance, Viral / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D006509:Hepatitis B / Q000188:drug therapy*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D012008:Recurrence
D019380:Anti-HIV Agents; D019259:Lamivudine