Absence of mutations in the YMDD motif/B region of the hepatitis B virus polymerase in famciclovir therapy failure

被引:32
作者
Günther, S
von Breunig, F
Santantonio, T
Jung, MC
Gaeta, GB
Fischer, L
Sterneck, M
Will, H
机构
[1] Bernhard Nocht Inst Trop Med, D-20359 Hamburg, Germany
[2] Univ Hamburg, Heinrich Pette Inst Expt Virol & Immunol, D-2000 Hamburg, Germany
[3] Univ Bari, Clin Malattie Infettive, I-70121 Bari, Italy
[4] Univ Munich, Klinikum Grosshadern, Med Klin 2, D-80539 Munich, Germany
[5] Univ Naples 2, Clin Malattie Infettive, Naples, Italy
[6] Univ Hamburg, Krankenhaus Eppendorf, Chirurg Klin, D-2000 Hamburg, Germany
关键词
antiviral therapy; famciclovir; hepatitis B virus; lamivudine; mutation; viral polymerase;
D O I
10.1016/S0168-8278(99)80124-X
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background/Aims: Nucleoside analogues such as lamivudine and famciclovir are potent drugs for treatment of chronic hepatitis B virus infection, Breakthrough infections during lamivudine therapy are associated with mutations in the YMDD motif and putative B region of the HBV polymerase. This study investigated whether failure of famciclovir therapy is also associated with presence or emergence of particular mutations in the HBV polymerase. Methhods: We analyzed longitudinally the sequence of the priming and polymerase domain in seven patients with primary non-response to therapy and two patients with a breakthrough during therapy. Two patients who responded to therapy served as a control. Results: The YMDD motif and the B region were conserved in all isolates. V-->I changes at position 555 just downstream of the YMDD motif were observed before and during therapy in a virus subpopulation of two patients with a primary non-response. In patients with a breakthrough, 378-V-->I and 424-N-->D mutations emerged in the N terminal part of the polymerase domain during follow-up. Lamivudine rescue therapy initiated in four patients, including a patient infected with YMDD(555-V-->I) variants, efficiently reduced viremia, Conclusions: These data indicate that failure of famciclovir therapy can occur independently of mutations in the YMDD motif or B region of the HBV polymerase and provide a rationale for rescue therapy with lamivudine.
引用
收藏
页码:749 / 754
页数:6
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