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 1mg+ADV 10mg (n=138), ADV+LAM 100mg (n=137), or ETV (n=140). Results: At week 48, there was no significant difference in the primary endpoint of HBV-DNA<50IU/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<50IU/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.
|Number of pages||9|
|Journal||Journal of Gastroenterology and Hepatology (Australia)|
|Publication status||Published - 2014 Jul|
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