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J Infect Dis. 2016 Jan 1;213(1):39-48. doi: 10.1093/infdis/jiv363. Epub 2015 Jul 1.

Combined Analysis of the Prevalence of Drug-Resistant Hepatitis B Virus in Antiviral Therapy-Experienced Patients in Europe (CAPRE).

Author information

1
Department of Medical Microbiology, University Medical Centre Utrecht Department of Virology, Erasmus Medical Centre, Rotterdam, The Netherlands.
2
Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Italy.
3
Department of Virology, Erasmus Medical Centre, Rotterdam, The Netherlands.
4
Servicio de Microbiología, Hospital San Cecilio, Instituto de Investigación Biosanitaria ibs. GRANADA, Hospitales Universitarios de Granada, Spain.
5
Liver Disease Centre, Sheba Medical Centre, Ramat Gan, Israel.
6
Department of Medical Microbiology, University Medical Centre Utrecht.
7
Hygiene Unit, IRCCS AOU San Martino - IST, Genoa.
8
Malattie Infettive, Seconda Università degli studi di Napoli, Naples, Italy.
9
Laboratory of Retrovirology, CRP-Santé, Luxembourg.
10
Molecular Diagnostics Laboratory, Hospital of Infectious Diseases, Warsaw, Poland.
11
Institute of Virology, University of Cologne, Germany.
12
Clinic of Infectious Diseases and Clinical Microbiology, Izmir Tepecik Education and Research Hospital, Turkey.
13
Section of Molecular Diagnostics, Clinical Biochemistry, Aalborg University Hospital, Denmark.
14
Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Serbia.
15
Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Slovenia.
16
Service de Microbiologie, University Paris Diderot, Hôpital Saint Louis, France.
17
Lugi Sacco Hospital, Milan, Italy.
18
National HIV Reference Laboratory, Central Virology Laboratory, Ministry of Health, Tel Hashomer, Ramat Gan, Israel.
19
Molecular Diagnostics Laboratory, National Institute for Infectious Diseases Matei Bals, Bucharest, Romania.
20
National Retrovirus Reference Centre, Department of Hygiene, Epidemiology and Medical Statistics, Faculty of Medicine, National and Kapodistrian University of Athens, Greece.
21
Department for Virology, Medical University of Vienna, Austria.
22
Department of Virology, Norwegian Institute of Public Health, Oslo, Norway.
23
Institute of Microbiology, Polyclinic for Laboratory Diagnostics, University Clinical Centre Tuzla, Bosnia and Herzegovina.
24
Virology Laboratory, Centre Hospitalier Régional et Université Victor Segalen, Bordeaux, France.
25
Institute of Virology, University-Hospital, University Duisburg-Essen, Germany.
26
University of Zagreb School of Medicine and University Hospital for Infectious Diseases "Dr Fran Mihaljevic", Croatia.
27
Department of Infectious Diseases, Copenhagen University Hospital, Denmark.
28
Refik Saydam National Public Health Agency, Ankara, Turkey.

Abstract

BACKGROUND:

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 hepatitis B virus DNA in European tertiary referral centers.

RESULTS:

Data from 1568 patients were included. The majority (73.8%) were 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 < .001).

CONCLUSIONS:

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.

KEYWORDS:

antiviral drug resistance; genotypic resistance testing; hepatitis B virus; nucleos(t)ide analogs

PMID:
26136470
DOI:
10.1093/infdis/jiv363
[Indexed for MEDLINE]

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