JAC Advance Access originally published online on June 7, 2007
Journal of Antimicrobial Chemotherapy 2007 60(2):448-449; doi:10.1093/jac/dkm199
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Correspondence |
Does pre-treatment with lamivudine prime for adefovir resistance of hepatitis B virus infection?
1 Heinrich-Pette-Institute, Hamburg, Germany 2 Institute of Medical Virology, University of Giessen, Germany 3 Institute for Medical Microbiology, Immunology, and Parasitology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany
* Corresponding author. Tel: +49-228-28711697; Fax: +49-228-28714433; E-mail: schildgen{at}mibi03.meb.uni-bonn.de
Keywords: antiviral therapy , HBV , resistance
We read the recent case report by Ni Laoi et al.1 with great interest. The authors report on a chronic hepatitis B virus (HBV) infection resistant to lamivudine and adefovir. During antiviral therapy, lamivudine was replaced by adefovir due to the emergence of resistant virus. The subsequent therapy with adefovir was ineffective and did not decrease the viraemia to a significant extent despite reliable compliance. Analysis of the virus genomes did not reveal any mutation known to be associated with adefovir resistance, but the previous treatment with lamivudine had induced the mutation rtA181V. Mutation at this position is reported to confer resistance to lamivudine and the rtA181T exchange is suspected to mediate adefovir resistance although the experimental proof is still lacking.
In our view, the report by Ni Laoi et al.1 in concert with earlier publications2–8 underscores the urgent need for a paradigm change in antiviral therapy of chronic HBV for the following two reasons: (i) it reflects an increasing problem; and (ii) cases of initial non-response to antiviral drugs occur frequently rather than being rare events. Thus, the initial non-response to antiviral therapy is only the peak of an iceberg whose extent is not fully known. The list of mutations mediating resistance to antiviral therapy is far from being complete. The increasing number of reverse transcriptase (RT) inhibitors licensed for antiviral therapy will further increase both the number and complexity of resistance mutations. These issues are of great medical importance since they might result in emergence of mutant viruses escaping vaccine protection and diagnosis. Thus, we fully support the recommendation by Ni Laoi et al.1 that genotypic analysis and sequencing of the RT polymerase domain of the HBV strains should become a routine part of an individualized antiviral therapy. Also, the role of host factors contributing to drug resistance such as cellular metabolic (dys-) functions9 should be elucidated. To defeat the problem of resistance mutations and its consequences, we would like to propose a systematic approach for data monitoring and mining of therapy in HBV antiviral resistance. This approach should combine present and future knowledge and experience and requires union of both national and international forces and groups active in the field.
None to declare.
References
1
Ni Laoi B, Herra C, Norris S, et al. Hepatitis B virus resistance to adefovir in a nucleotide naive patient with chronic hepatitis B virus infection. J Antimicrob Chemother (2007) 59:807–9.
2 Angus P, Vaughan R, Xiong S, et al. Resistance to adefovir dipivoxil therapy associated with the selection of a novel mutation in the HBV polymerase. Gastroenterology (2003) 125:292–7.[CrossRef][Web of Science][Medline]
3 Bartholomeusz A, Kuiper M, Angus P, et al. Molecular analysis of HBV polymerase mutations associated with dual adefovir and lamivudine resistance. J Hepatol (2006) 44:S179.
4
Schildgen O, Sirma H, Funk A, et al. Variant of hepatitis B virus with primary resistance to adefovir. N Engl J Med (2006) 354:1807–12.
5 Schildgen O, Helm M, Gerlich W. Nonresponse to adefovir: host or virus dependent? J Clin Virol (2006) 37:327–8.[CrossRef][Web of Science][Medline]
6 van Bommel F, Wunsche T, Mauss S, et al. Comparison of adefovir and tenofovir in the treatment of lamivudine-resistant hepatitis B virus infection. Hepatology (2004) 40:1421–5.[CrossRef][Web of Science][Medline]
7 Villet S, Pichoud C, Villeneuve JP, et al. Selection of a multiple drug-resistant hepatitis B virus strain in a liver-transplanted patient. Gastroenterology (2006) 131:1253–61.[CrossRef][Web of Science][Medline]
8
Ni Laoi B, Herra C, Norris S, et al. First report of genotypic resistance to adefovir in chronic HBV in the Republic of Ireland. J Antimicrob Chemother (2006) 57:1009–10.
9 Tillmann HL. Antiviral therapy and resistance with hepatitis B virus infection. World J Gastroenterol (2007) 13:125–40.[Web of Science][Medline]
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