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 (HEV) DNA polymerase. Its over all efficiency is clearly hampered by relapse at discontinuation and by ris k of genotypic resistance. We describe herein the first cases of HBV resist ance to lamivudine in kidney recipients and hemodialyzed patients. Methods. We analyzed 26 HBV-infected kidney recipients and five hemodialyze d patients treated with lamivudine who kecame serum HBV DNA-negative (by Di gene test). The biological and virological follow-up identified breakthroug h as defined by the reappearance of serum HBV DNA, In two cases of breakthr ough, HBV DNA was amplified and sequenced through the polymerase domain, in cluding the YMDD motif, before the beginning of treatment and at time of br eakthrough to determine genotypic mutations. Results. Ten breakthroughs (reappearance of serum HBV DNA) were observed af ter a median follow-up of 11 months in eight kidney recipients and two hemo dialyzed patients after a median duration of treatment of 16.5 (from 4 to 3 1) months of treatment. Previous HBe/anti-HBe seroconversion was not observ ed in the patients who escaped. In two kidney recipients, the comparison of HBV-DNA sequences before the treatment and after the breakthrough identifi ed in one case a mutation of the highly conserved YMDD motif (YVDD), wherea s in the second case, no genotypic mutation was observed in the sequenced r egion. Conclusion. We report the first cases of HBV genotypic resistance to lamivu dine in kidney recipients and hemodialysis patients. Genotypic resistance i s observed after 4-31 months of therapy. The YMDD mutation does not account for all cases of virological escape.