A review of the one-year incidence of resistance to lamivudine in the treatment of chronic hepatitis B

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 oneyear 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.

Safety of tumor necrosis factor α blockers in hepatitis B virus occult carriers (hepatitis B surface antigen negative/anti–hepatitis B core antigen positive) with rheumatic diseases

“…However, the use of lamivudine in patients receiving an extended course of immunosuppressive therapy has an uncertain benefit versus risk rate, as its prolonged employ is associated with the emergence of lamivudine-resistant mutants (30,33,50). Therefore, lamivudine administration as universal prophylactic therapy in all patients with previous contact with HBV should be considered with caution.…”

“…On the other hand, many cases have been described in which TNF blockade, either in association with lamivudine prophylactic therapy or not, did not lead to HBV reactivation (6,(25)(26)(27)(28)(29)(30), and recently a retrospective study showed no reactivation during anti-TNF␣ therapy (31). The use of lamivudine to prevent HBV reactivation is recommended in HBsAg-positive patients undergoing immunosuppressive therapies, including anti-TNF␣ drugs (4,32), but its use can lead to viral resistance (33). There are no prospective studies regarding HBV reactivation and TNF␣ blocker therapy, and in particular few data are available about HBsAg-negative, antiHBc-positive patients.…”

Hepatitis B virus management to prevent reactivation after chemotherapy: a review

“…However, in this setting, cessation of antiviral therapy should be followed by monitoring of ALT and HBV DNA for 6–12 months to minimize the risk of reactivation. The rate of genotypic resistance (mutations that confer resistance) to lamivudine in patients with virologic breakthrough has been reported to be up to 15%[70], and such mutations have resulted in poor outcomes in cancer patients who received lamivudine prophylaxis during chemotherapy and for 6 months after stem cell transplantation [71]. …”

Hepatitis B: An Overlooked STI, a Silent Threat, a Global Disease

“…In fact, lamivudine was the drug tested on HIV patients that coincidentally showed dramatic declines in HBV titers in those with coinfection. While it has negligible side effects and is effective in certain strains, it has a high incidence of resistance; although, there have been extensive debates on the difference in assays [19] and on the baseline HBV DNA [20]. Adefovir was approved in 2002 and had particular efficacy in HBeAg negative patients, but carried a risk of long-term renal toxicity and still a failure rate of almost 30%.…”