HBV genotypic resistance to lamivudine in kidney recipients and hemodialyzed patients.
BACKGROUND
Lamivudine is a potent inhibitor of human immunodeficiency virus reverse transcriptase and hepatitis B virus (HBV) DNA polymerase. Its overall efficiency is clearly hampered by relapse at discontinuation and by risk of genotypic resistance. We describe herein the first cases of HBV resistance to lamivudine in kidney recipients and hemodialyzed patients.


METHODS
We analyzed 26 HBV-infected kidney recipients and five hemodialyzed patients treated with lamivudine who became serum HBV DNA-negative (by Digene test). The biological and virological follow-up identified breakthrough as defined by the reappearance of serum HBV DNA. In two cases of breakthrough, HBV DNA was amplified and sequenced through the polymerase domain, including the YMDD motif, before the beginning of treatment and at time of breakthrough to determine genotypic mutations.


RESULTS
Ten breakthroughs (reappearance of serum HBV DNA) were observed after a median follow-up of 11 months in eight kidney recipients and two hemodialyzed patients after a median duration of treatment of 16.5 (from 4 to 31) months of treatment. Previous HBe/anti-HBe seroconversion was not observed in the patients who escaped. In two kidney recipients, the comparison of HBV-DNA sequences before the treatment and after the breakthrough identified in one case a mutation of the highly conserved YMDD motif (YVDD), whereas in the second case, no genotypic mutation was observed in the sequenced region.


CONCLUSIONS
We report the first cases of HBV genotypic resistance to lamivudine in kidney recipients and hemodialysis patients. Genotypic resistance is observed after 4-31 months of therapy. The YMDD mutation does not account for all cases of virological escape.
Fontaine
H
H
Unité d'Hépatologie, Hôpital Necker, Paris, France.
Thiers
V
V
Chrétien
Y
Y
Zylberberg
H
H
Poupon
R E
RE
Bréchot
C
C
Legendre
C
C
Kreis
H
H
Pol
S
S
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D004279:DNA, Viral / Q000097:blood; D004352:Drug Resistance, Microbial; D005260:Female; D005500:Follow-Up Studies; D006509:Hepatitis B / Q000188:drug therapy* / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D016030:Kidney Transplantation; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D014766:Viremia
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine