title: Unusual selection of rtA181V HBV mutants cross-resistant to adefovir following prolonged lamivudine monotherapy: report of two cases.
abstract: Development of hepatitis B virus (HBV)-resistant strains following nucleos(t)ide analogue treatment is a major concern. The A181V mutation within the reverse transcriptase (RT) of HBV has been shown to be associated with HBV resistance to adefovir dipivoxil (ADV), and its level of sensitivity to other nucleos(t)ide analogues is an important issue. This article reports two cases of chronically HBV infected patients who developed rtA181V HBV mutants following lamivudine (LAM) monotherapy. This was subsequently associated with virological breakthrough under LAM monotherapy or LAM/ADV bi-therapy, which were rescued by tenofovir disoproxil fumarate treatment. These observations suggest that rtA181V mutation may unusually emerge under LAM monotherapy, and may be associated with cross resistance to LAM and ADV, but remains sensitive to tenofovir disoproxil fumarate. Moreover, they highlight that HBV sequence analysis is an essential tool to optimize therapeutic management of HBV chronic infection in clinical practice in order to choose the appropriate nucleos(t)ide analogues.
authors.affiliation: Service d'Hépato-gastroentérologie, Centre Hospitalier Universitaire Conception, Marseille, France. rene.gerolami@ap-hm.fr
authors.forename: Rene
authors.initials: R
authors.lastname: Gerolami
authors.forename: Marc
authors.initials: M
authors.lastname: Bourliere
authors.forename: Philippe
authors.initials: P
authors.lastname: Colson
authors.forename: Philippe
authors.initials: P
authors.lastname: Halfon
authors.forename: Patrick
authors.initials: P
authors.lastname: Borentain
authors.forename: Mireille
authors.initials: M
authors.lastname: Henry
authors.forename: Daniele
authors.initials: D
authors.lastname: Botta
authors.forename: Vincent
authors.initials: V
authors.lastname: Thibault
authors.forename: Hacene
authors.initials: H
authors.lastname: Khiri
authors.forename: Catherine
authors.initials: C
authors.lastname: Tamalet
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D004279:DNA, Viral / Q000097:blood; D004334:Drug Administration Schedule; D024921:Drug Resistance, Multiple, Viral; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D009154:Mutation; D063065:Organophosphonates / Q000494:pharmacology*; D012641:Selection, Genetic
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D019259:Lamivudine; C053001:adefovir; D000225:Adenine