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.