Hie-Won Hann1, Vicki L Gregory, Jonathan S Dixon, Keith F Barker. 1. Division of Gastroenterology and Hepatology, Department of Medicine, Jefferson Medical College, 1025 Walnut Street, Philadelphia, PA, 19107, USA, Hie-Won.Hann@jefferson.edu.
Abstract
PURPOSE: The development of antiviral resistance is a recognized challenge to successful treatment of chronic hepatitis B (CHB), but it has been difficult to establish an accurate estimate of its incidence due to a number of factors: (a) lack of an accepted definition of antiviral resistance; (b) lack of a standardized assay to assess resistance; and (c) lack of consensus on patient selection criteria for resistance testing. Lamivudine, an effective and well-established antiviral agent, has been reported to show one-year resistance rates in CHB ranging from 6% to 32%, but methodologies used to calculate these rates vary considerably. This article reviews the clinical, statistical, and laboratory methodologies of clinical studies reporting one-year rates of antiviral resistance to lamivudine in CHB. METHODS: Studies reporting one-year resistance rates to lamivudine in CHB were analyzed for methodologic differences and their influence on reported resistance rates. RESULTS: Studies using only a genotypic definition of resistance reported one-year rates ranging from 14% to 32%. Studies assessing genotypic resistance in patients with evidence of virologic breakthrough reported much lower one-year resistance rates of 6.4-15.4%. CONCLUSIONS: It is important when comparing resistance rates to antiviral drugs in CHB to consider the methodology and definition of resistance used because this can dramatically influence the results.
PURPOSE: The development of antiviral resistance is a recognized challenge to successful treatment of chronic hepatitis B (CHB), but it has been difficult to establish an accurate estimate of its incidence due to a number of factors: (a) lack of an accepted definition of antiviral resistance; (b) lack of a standardized assay to assess resistance; and (c) lack of consensus on patient selection criteria for resistance testing. Lamivudine, an effective and well-established antiviral agent, has been reported to show one-year resistance rates in CHB ranging from 6% to 32%, but methodologies used to calculate these rates vary considerably. This article reviews the clinical, statistical, and laboratory methodologies of clinical studies reporting one-year rates of antiviral resistance to lamivudine in CHB. METHODS: Studies reporting one-year resistance rates to lamivudine in CHB were analyzed for methodologic differences and their influence on reported resistance rates. RESULTS: Studies using only a genotypic definition of resistance reported one-year rates ranging from 14% to 32%. Studies assessing genotypic resistance in patients with evidence of virologic breakthrough reported much lower one-year resistance rates of 6.4-15.4%. CONCLUSIONS: It is important when comparing resistance rates to antiviral drugs in CHB to consider the methodology and definition of resistance used because this can dramatically influence the results.
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