Combined Analysis of the Prevalence of drug Resistant HBV in antiviral therapy Experienced patients in Europe (CAPRE) - L.E. Hermans1,2,*,
- V. Svicher3,*,
- S.D. Pas2,
- R. Salpini3,
- M. Alvarez4,
- Z. Ben Ari20,
- G. Boland1,
- B. Bruzzone5,
- N. Coppola6,
- C. Seguin-Devaux7,
- T. Dyda8,
- F. Garcia4,
- R. Kaiser9,
- S. Köse10,
- H. Krarup11,
- I. Lazarevic12,
- M.M. Lunar13,
- S. Maylin14,
- V. Micheli15,
- O. Mor16,
- S. Paraschiv17,
- D. Paraskevis18,
- M. Poljak13,
- E. Puchhammer-Stöckl19,
- F. Simon14,
- M. Stanojevic12,
- K. Stene-Johansen21,
- N. Tihic22,
- P. Trimoulet23,
- J. Verheyen24,
- A. Vince25,
- N. Weis26,
- T. Yalcinkaya27,
- S. Zidovec Lepej26,
- C. Perno3,
- C.A.B. Boucher2 and
- A.M.J. Wensing1
- on behalf of the HEPVIR working group of the European Society for translational antiviral research (ESAR)
- Author Affiliations - 1Department of Medical Microbiology, University Medical Centre Utrecht, Utrecht, The Netherlands
- 2Department of Virology, Erasmus Medical Centre, Rotterdam, The Netherlands
- 3Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata”, Rome, Italy
- 4Servicio de Microbiología, Hospital San Cecilio, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada, Granada, Spain
- 5Hygiene Unit, IRCCS AOU San Martino - IST, Genoa, Italy
- 6Malattie Infettive, Seconda Università degli studi di Napoli, Naples, Italy
- 7Laboratory of Retrovirology, CRP-Santé, Luxembourg, Luxembourg
- 8Molecular Diagnostics Laboratory, Hospital of Infectious Diseases, Warsaw, Poland
- 9Institute of Virology, University of Cologne, Cologne, Germany
- 10Izmir Tepecik Education and Research Hospital, Clinic of Infectious Diseases and Clinical Microbiology, Izmir, Turkey
- 11Section of Molecular Diagnostics, Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
- 12Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
- 13Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- 14Service de Microbiologie, University Paris Diderot, Hôpital Saint Louis, Paris, France
- 15“L. Sacco” Hospital, Milan, Italy
- 16National HIV Reference Laboratory, Central Virology Laboratory, Ministry of Health, Tel Hashomer, Ramat Gan, Israel
- 17Molecular Diagnostics Laboratory, National Institute for Infectious Diseases “Matei Bals”, Bucharest, Romania
- 18National Retrovirus Reference Centre, Department of Hygiene, Epidemiology and Medical Statistics, Faculty of Medicine, National and Kapodistrian University of Athens, Athens, Greece
- 19Department for Virology, Medical University of Vienna, Vienna, Austria
- 20Liver Disease Centre, Sheba Medical Centre, Ramat Gan, Israel
- 21Department of Virology, Norwegian Institute of Public Health, Oslo, Norway
- 22Institute of Microbiology, Polyclinic for Laboratory Diagnostics, University Clinical Centre Tuzla, Tuzla, Bosnia and Herzegovina
- 23Virology Laboratory, Centre Hospitalier Régional et Université "Victor Segalen", Bordeaux, France
- 24Institute of Virology, University-Hospital, University Duisburg-Essen, Essen, Germany
- 25University of Zagreb School of Medicine and University Hospital for Infectious Diseases “Dr. Fran Mihaljevic”, Zagreb, Croatia
- 26Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark
- 27Refik Saydam National Public Health Agency, Ankara, Turkey
- Corresponding author: Annemarie M.J. Wensing, MD PhD, University Medical Centre Utrecht – Virology, Dept of Medical Microbiology G04.614, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands, Phone: +31 88 7556526, Fax: +31 88 7555426, [email protected]
Abstract Introduction. European guidelines recommend treatment of chronic Hepatitis B virus infection (CHB) with the nucleos(t)ide analogs (NAs) entecavir or tenofovir. However, many European CHB patients have been exposed to other NAs, which are associated with therapy failure and resistance. The CAPRE study was performed to gain insight in prevalence and characteristics of NA resistance in Europe. Methods. A survey was performed on genotypic resistance testing results acquired during routine monitoring of CHB patients with detectable serum HBV-DNA in European tertiary referral centres. Results. Data of 1568 patients was included. The majority (73.8%) was exposed to lamivudine monotherapy. Drug resistant strains were detected in 52.7%. The most frequently encountered primary mutation was M204V/I (48.7%), followed by A181T/V (3.8%) and N236T (2.6%). In patients exposed to entecavir (n=102), full resistance was present in 35.3%. Independent risk factors for resistance were age, viral load and lamivudine exposure (p<0.001). Conclusion. These findings support resistance testing in cases of apparent NA therapy failure. This survey highlights the impact of exposure to lamivudine and adefovir on development of drug resistance and cross-resistance. Continued use of these NAs needs to be reconsidered at a pan-European level.
- © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].
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发表于 2015-7-4 06:35
