Clonal analysis of the quasispecies of antiviralresistant HBV genomes in patients with entecavir resistance during rescue treatment and successful treatment of entecavir resistance with tenofovir


Karatayli E., İDİLMAN R., Karatayli S. C., Cevik E., Yakut M., Seven G., ...Daha Fazla

Antiviral Therapy, cilt.18, sa.1, ss.77-85, 2013 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 18 Sayı: 1
  • Basım Tarihi: 2013
  • Doi Numarası: 10.3851/imp2294
  • Dergi Adı: Antiviral Therapy
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.77-85
  • Ankara Üniversitesi Adresli: Evet

Özet

Background: Clonal analysis of quasispecies of resistant HBV genomes in patients with entecavir (ETV) resistance receiving lamivudine (3TC) plus adefovir (ADV) rescue therapy has never been performed. Methods: A sample of 10 patients with ETV resistance who were switched to 3TC+ADV treatment were analysed for changes in viral quasispecies. Serum samples at baseline, and at months 3 and 6 of 3TC+ADV treatment could be clonally analysed in 7 of 10 patients; 3-82 clones per sample (total 1,068 clones, mean 63) were sequenced. Results: 3TC+ADV therapy led to a modest decline in HBV DNA. Almost all clones had L180M and M204V 3TC resistance mutations before and during combination therapy. All clones had ≥1 of the S202G, T184F, T184A, T184L, T184I and M250V ETV resistance mutations. The percentages of detected clones bearing 3TC (rtL180M and rtM204V) and ETV mutations did not change with rescue 3TC+ADV therapy. In 7 of 8 patients with detectable HBV DNA (median 5.17 log 10 copies/ml) after a median 24 months of ADV therapy, HBV DNA became undetectable with 3TC plus tenofovir after 6 months of treatment. Conclusions: In patients with ETV resistance tenofovir is effective. Clonal analysis data indicate no selection of speciic HBV mutants during rescue 3TC+ADV. © 2013 International Medical Press.