Avoiding and managing lamivudine resistance in chronic hepatitis B: current approaches and potential strategies including pegylated interferon

Abstract

Since its approval for the treatment of chronic hepatitis B in 1998, lamivudine (LAM) has been used extensively throughout the world, because of its relatively low costs and favourable tolerability. However, clinical trials and cohort studies have demonstrated that a high rate of resistance to this drug develops and, as a result, it is no longer included as a first-line therapy in most current treatment guidelines. Nevertheless, because of its low cost, this drug continues to be used in many countries and the pool of patients who have developed resistance to LAM continues to increase. Thus, there is a clear need to develop coherent management strategies to treat such patients as well as limit the emergence of resistance in the first instance. The purpose of this review is to highlight the need to aim for long-term treatment success while limiting the emergence of drug resistance and its consequences for the future. In addition to add-on/switch strategies with other nucleos(t)ide analogs, currently available data suggest that interferon-based therapies, with their potential to induce a sustained response, are worthy of consideration not only for reducing de novo resistance but as an option for the management of those patients in whom drug resistance has already developed.

Update on rescue therapies in patients with lamivudine-resistant chronic hepatitis B

“…One of the core concepts is that active virus replication is required to develop resistant strains 14,18. Primary non-response to treatment, defined as a <1 log 10 drop in HBV DNA at week 12, as well as partial response (still detectable HBV DNA levels after 24 weeks of treatment) are both risk factors in developing anti-HBV resistance 14.…”

“…Testing for resistance at baseline can help predict response to LAM, and therefore determine who is most appropriate for treatment 18. This may be especially useful in those with a prior treatment history, as their likelihood of LAM resistance is significantly higher.…”

Cost-effectiveness analysis of different rescue therapies in patients with lamivudine-resistant chronic hepatitis B in China

“…Fifth, the current analysis did not include interferon-based strategies for dealing with LAM resistance. Some studies have suggested that a significant proportion of patients with LAM resistance who switched to pegIFNa-2a from LAM had a similar response to pegIFNa-2a as treatment-naïve patients [6]. Sixth, the utility scores for patients with LAM-resistant and multi-resistant CHB were assumed to be equal to those for naïve CHB.…”

“…Although multiple rescue strategies for LAM-resistant CHB have been evaluated in clinical trials, the most commonly recommended strategies are ADV monotherapy (10 mg/day), combination therapy using LAM (100 mg/day) and ADV (10 mg/day), ETV monotherapy (1 mg/day) and TDF monotherapy (300 mg/day) [6]. Therefore, these 4 rescue strategies were included to compare their cost and effectiveness over time.…”

“…[4] However, the high daily cost of ETV and TDF limits their widespread use in areas with limited health resources, such as in China [5]. LAM is still accepted as the main antiviral agent in these areas, largely because of its relatively low daily cost and well-established safety and efficacy profile [6]. However, long-term use of LAM is associated with a high rate of resistance (up to 70% by the end of 5 years) due to mutation at the YMDD motif [7].…”