HIV-GRADE HBV-Tool M. Obermeier 04/ 2008 Medizinisches Labor Berg - PowerPoint PPT Presentation

HIV-GRADE HBV-Tool M. Obermeier 04/ 2008 Medizinisches Labor Berg

Daten- bank HIVdb HIVdb Core Module HIV-SEQ Basis: Stanford HIVdb HIV-ALG 4/ 2008

Analysis flowchart Sequence data Mutation list Alignment on Pan- Genotype Consensus Identification of available genes Identification of genotype and re-alignment on genotype specific consensus-sequence Identification of mutations Analysis of mutations based on the algorithm Detailled output Tabular output 4/ 2008

Algorithm Specification Interface (ASI) � Rules based algorithms can be described in xml-format HBV-ruleset can be described in a format that is compatible to other algorithms 4/ 2008

HBV drug resistance mutations 4/ 2008

Algorithm RT-Inhibitors: Lamivudine Resistance Possible Resistance � 204ISV � 180M � 173L � 80VI Adefovir Resistance Possible Resistance � 236T � 233V � A181STV 4/ 2008

Algorithmus Entecavir Resistance Possible Resistance � 204IV and 1 of (169T, 184AGILS, 202CGI, � 1 of (169T, 184AGILS, 202CGI, 250IV) � 204IV and 1 of (173L, 180M) 250IV) Comment: 204VI => A mutation M204VI alone only slightly impairs the susceptibility to entecavir, however the dose of entecavir should be increased according to the manufacturers instructions Tenofovir Resistance Possible Resistance � 194T 4/ 2008

Possible Resistance � 180M Algorithm Telbivudine Resistance � 204ISV 4/ 2008

� 1 of (137W, 141W, 144HA, 145R, 147S) HBs-antigen-escape Algorithm HBs-escape 4/ 2008

Sequence input 4/ 2008

Output of sequence length and genotype 4/ 2008

Output of RT-Alignment 4/ 2008

Output of HBsAg alignment 4/ 2008

Analysis 4/ 2008

Analysis 4/ 2008

Analysis 4/ 2008

Patient BN � HIV Coinfected � Therapy: TDF/ FTC, DRV, MVC � HIV-VL < 50 Cop./ ml � HBV-VL: 20.000.000 IU/ ml 4/ 2008

Patient BN 4/ 2008

HIV-GRADE e.V. � Thomas Berg, Medizinisches Labor Dr. Berg, Berlin � Patrick Braun, PZB Aachen � Martin Däumer, Institut für Immunologie und Genetik � Josef Eberle, Pettenkofer-Institut, München � Robert Ehret, PZB Aachen � Rolf Kaiser, Institut für Virologie, Köln � Klaus Korn, NRZ für Retroviren, Erlangen � Harm Müller, Fenner-Labor, Hamburg � Martin Stürmer, Institut für Medizinische Virologie, Frankfurt � Hauke Walter, NRZ für Retroviren, Erlangen � Eva Wolf, MUC Research München