HBV Testing for drug resistance and resistance interpretation - - PowerPoint PPT Presentation

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HBV Testing for drug resistance and resistance interpretation - - PowerPoint PPT Presentation

HBV Testing for drug resistance and resistance interpretation Martin Dumer Institute of Immunology and Genetics Kaiserslautern Genome of HBV HBV drug resistance testing technical approach 0.25 Product 1 (base 377 to 864) For: 5


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HBV

Testing for drug resistance and resistance interpretation

Martin Däumer Institute of Immunology and Genetics Kaiserslautern

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Genome of HBV

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  • N236T
  • 0.25
  • 0.87

Product 1 (base 377 to 864) For: 5’GGATGTGTCTGCGGCGTTT3’ Rev: 5’ACCCCATCTTTTTGTTTTGTTAGG3’ Product 2 (base 252 to 819) For: 5’AGACTCGTGGTGGACTTCTCT3’ Rev: 5’CAAAAGAAAATTGGTAACAGCGGTA3’

Allen et al., 1998

HBV drug resistance testing – technical approach

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Editing: Seqman (Lasergene)

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HBV Resistance Mutations

845 a.a.

Terminal protein Spacer Pol/ RT RNaseH

A B C E D YMDD GVGLSPFLLA I(G) II(F)

Allen MI, et al. Hepatology. 1998;27:1670-1677. Qi X, et al. J Hepatol. 2004;40(suppl 1):20- 21. Tenney D, et al. Antimicrob Agents Chemother. 2004;48:3498-3507. Tyzeka [package insert]. Lai CL, et al. Gastroenterology. 2005;129:528-536. Schildgen O, et al. N Engl J Med. 2006;354:1807-1812. Locarnini S. 2006 IDRW. Abstract P2.

rtL80V/ I rtV173L rtL180M rtA181T/ V rtN236T rtl233V ? rtM204V/ I rtS202G/ C rtT184S/ A/ I / L ETV resistance rtL180M rtM204I LdT resistance rtL80V/ I rtL180M TDF resistance rtA194T rtM204V rtL180M rtM204V/ I / S LAM resistance ADV resistance rtM250I / V

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HBV genotypes- worldwide distribution

  • Schaefer, J Viral Hep 2005
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E D G A B

HBV genotypes - Cologne data

■genotype D is predominating

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Genafor/ Arevir HBV drug resistance interpretation tool [genafor.org]

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Genafor/ Arevir HBV drug resistance interpretation tool

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Genafor/ Arevir HBV drug resistance interpretation tool

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  • Joachim Selbig,

MPI für Molekulare Pflanzenphysiologie Golm und Universität Potsdam Joachim Büch, Andre Altmann, Thomas Lengauer, MPI für Informatik Saarbrücken Rolf Kaiser, Nadine Sichtig, Saleta Sierra Aragon, Melanie Balduin, Eugen Schülter, Herbert Pfister, Institut für Virologie, Gerd Fätkenheuer, Innere Medizin I, Universitätsklinik zu Köln Ulrike Schuldenzucker Europa Fachhochschule Fresenius, Köln Klaus Korn, Barbara Schmidt, Hauke Walter, Nationales Referenzzentrum für Retroviren, Universität Erlangen-Nürnberg Patrick Braun, Robert Ehret, Heribert Knechten Praxiszentrum Blondelstraße, Aachen Bernd Kupfer, Bertfried Matz, Karl E. Schneweis, Med. Mikrobiologie Jürgen K. Rockstroh, Medizinische Klinik I, Universitätsklinik Bonn Mark Oette, Claudia Müller, Klinik f. Gastroenterologie, Hepatologie u. Infektiologie, Universitätsklinikum Düsseldorf

www.genafor.org