Entecavir plus adefovir versus adefovir plus lamivudine in hepatitis B virus e antigen-positive, lamivudine-resistant chronic hepatitis B

Abstract

Background and Aim In areas of the world where tenofovir disoproxil fumarate is not marketed, adefovir (ADV) + lamivudine (LAM) is recommended and widely used for LAM-resistant chronic hepatitis B (CHB). This study hypothesizes that entecavir (ETV) + ADV, where both components are active against LAM-resistant hepatitis B virus (HBV), will provide greater antiviral potency than ADV + LAM where only ADV is active. Methods Open-label, randomized trial in hepatitis B virus e antigen-positive LAM-experienced CHB patients with LAM resistance treated with ETV 1 mg + ADV 10 mg (n = 138), ADV + LAM 100 mg (n = 137), or ETV (n = 140). Results At week 48, there was no significant difference in the primary endpoint of HBV-DNA < 50 IU/mL between the treatment groups (25.4% [ETV + ADV] vs 19.7% [ADV + LAM], P = 0.2619; vs 16.4% [ETV], P = 0.1336). However, at week 96, rates of HBV-DNA < 50 IU/mL were significantly greater with ETV + ADV than with ADV + LAM (43.5% vs 28.5%; P = 0.0095). Rates of virologic breakthrough and resistance to ETV or ADV were low through week 96 with both combinations. The delayed benefit of ETV + ADV is likely related to the high baseline viremia in this cohort relating to continued LAM exposure after treatment failure. All three therapies had favorable safety profiles. Conclusions In patients with LAM-resistant HBV, ETV + ADV demonstrated greater antiviral efficacy than ADV + LAM and comparable safety over 2 years, and may therefore be a preferable treatment option for LAM-resistant CHB, especially in regions where alternative rescue therapies are not available. In highly viremic patients, the benefit of ETV + ADV became apparent after a longer treatment duration.