BMBF consortium: Hepatitis B therapies optimized by phenotypic evaluation (HOPE)
Project Aims 1. To validate the resistance profile of the HBV polymerase a as a biomarker 2. establish a phenotypic resistance test for HBV 3. establish databases on clinical courses, HBV genotypes and HBV phenotypes during antiviral treatment 4. correlate HBV genotypic analysis with phenotypic resistance profiles and clinical response to treatment 5. develop an interpretation system that allows rapid rating of clinical relevance (HBV ‐ Clino2Pheno) and antiviral resistance (HBV ‐ Geno2Pheno) of HBV mutants 6. implement the interpretation system into a commercial assay
Attendees: • Jim Uzgiris Siemens Molecular Diagnostics, Berkley • Christoph Petry Siemens Molecular Diagnostics, Cologne • T. Lengauer, Sebastian Beggel, Andre Altmann MPI Saarbruecken • U. Protzer, Ke Zhang Institute of Virology Christian Bach, TU München / Helmholtz Zentrum München • R. Kaiser, Maria Fraune, Uni Köln; Institute of Virology • D. Glebe, C. Bremer Uni Giessen, Institute of Virology • K. Wursthorn MHH, Clinics Gastroenterology & Hepatology • Florian von Bömmel Charite Berlin, Dept. Gastroenterology & Hepatology • Oliver Schildgen Hospital Mehrheim, Köln
Workpackage 1 • van Bömmel / Wursthorn – retrospective and prospective documentation and interpretation of ≥ 200 clinical courses of HBV infected patients under antiviral therapy – selection / definition of clinical cohorts – Sequence analysis of the HBV RT • Lu / Glebe / Kaiser: select samples for testing from serum banks • Kaiser : – establishment of data banks – data mining, consistency testing, statistical analysis • Schildgen / Protzer : – sequencing of the complete polymerase gene
Workpackage 2 • Protzer / Glebe – Comparison of different methods to obtain replication competent HBV genomes for subsequent cell based phenotypic assays – Comparison of transient transfection assays vs. stable cell lines vs. vector transfer of mutant HBV genomes to assess drug susceptibility – Establishment of an “ideal” phenotypic assay • Kaiser / Lu / Schildgen / Sirma / Protzer / Glebe : – 200 phenotypes – 400 phenotypes • Protzer / Glebe / Sirma : – Testing of the viral fitness and pathogenicity of HBV mutant strains by infection – Influence of antiviral drugs on HBV cccDNA
Workpackage 3 • Lengauer / Kaiser – support establishment of the data bank in WP 1 – statistical analysis of the databank – data analysis, development of a bioinformatic system – implementation of the system to optimize HBV antiviral therapy (public domain) • Petry / Uzgiris – integration of the bioinformatic system into the software of the commercial platform (True Gene?)
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