AbstractBackground 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.