Thomas Berg1, Fabien Zoulim2, Bernd Moeller3, Huy Trinh4, Patrick Marcellin5, Sing Chan6, Kathryn M Kitrinos7, Phillip Dinh7, John F Flaherty7, John G McHutchison7, Michael Manns8. 1. Sektion Hepatologie, Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Universitätsklinikum Leipzig, Leipzig, Germany. Electronic address: thomas.berg@medizin.uni-leipzig.de. 2. INSERM U1052 and Hospices Civils de Lyon, Lyon, France. 3. Private practice, Berlin, Germany. 4. Private practice, San Jose, CA, USA. 5. Service d'Hepatologie and INSERM CRB3, University of Paris, Hopital Beaujon, Pavillon Abrami, Paris, France. 6. Private practice, Flushing, NY, USA. 7. Gilead Sciences, Inc., Foster City, CA, USA. 8. Department of Gastroenterology, Hepatology and Endocrinology, Medical School of Hannover, Hannover, Germany.
Abstract
BACKGROUND & AIMS: Suboptimal virologic response to nucleos(t)ide analogs may represent a significant risk factor for resistance development in patients with chronic hepatitis B virus infection; treatment options have not been well studied. We evaluated long-term efficacy and safety of tenofovir alone and in combination with emtricitabine in a prospective, placebo-controlled trial in patients who remained viremic on adefovir therapy. METHODS:Hepatitis B e antigen-positive and -negative patients with hepatitis B virus DNA ⩾ 1000 copies/ml despite up to 96 weeks of adefovir were randomized to double-blind tenofovir or emtricitabine/tenofovir for 168 weeks. Patients with hepatitis B virus DNA ⩾ 400 copies/ml (⩾ 69IU/ml) at or after week 24 could switch to open-label emtricitabine/tenofovir. RESULTS: Overall, 90/105 (86%) patients (46/53 tenofovir and 44/52 emtricitabine/tenofovir) completed the 168-week study period, including 74/105 (70%) patients (35/53 tenofovir and 39/52 emtricitabine/tenofovir) who completed the study on their initial randomized treatment. Long-term viral suppression (hepatitis B virus DNA <400 copies/ml) was maintained at week 168 in 84% and 82% of patients receiving either emtricitabine/tenofovir combination or tenofovir monotherapy, respectively (non-completer equal to failure analysis). Baseline viral load as well as the presence of lamivudine and/or adefovir resistance-associated mutations at baseline had no impact on long-term treatment response. No resistance to tenofovir was observed through 168 weeks. Both treatments had a favorable safety profile. CONCLUSIONS:Tenofovir monotherapy is as effective as emtricitabine/tenofovir combination therapy in maintaining long-term viral suppression in patients with a suboptimal response to adefovir, and is well tolerated in this population.
RCT Entities:
BACKGROUND & AIMS: Suboptimal virologic response to nucleos(t)ide analogs may represent a significant risk factor for resistance development in patients with chronic hepatitis B virus infection; treatment options have not been well studied. We evaluated long-term efficacy and safety of tenofovir alone and in combination with emtricitabine in a prospective, placebo-controlled trial in patients who remained viremic on adefovir therapy. METHODS:Hepatitis B e antigen-positive and -negative patients with hepatitis B virus DNA ⩾ 1000 copies/ml despite up to 96 weeks of adefovir were randomized to double-blind tenofovir or emtricitabine/tenofovir for 168 weeks. Patients with hepatitis B virus DNA ⩾ 400 copies/ml (⩾ 69IU/ml) at or after week 24 could switch to open-label emtricitabine/tenofovir. RESULTS: Overall, 90/105 (86%) patients (46/53 tenofovir and 44/52 emtricitabine/tenofovir) completed the 168-week study period, including 74/105 (70%) patients (35/53 tenofovir and 39/52 emtricitabine/tenofovir) who completed the study on their initial randomized treatment. Long-term viral suppression (hepatitis B virus DNA <400 copies/ml) was maintained at week 168 in 84% and 82% of patients receiving either emtricitabine/tenofovir combination or tenofovir monotherapy, respectively (non-completer equal to failure analysis). Baseline viral load as well as the presence of lamivudine and/or adefovir resistance-associated mutations at baseline had no impact on long-term treatment response. No resistance to tenofovir was observed through 168 weeks. Both treatments had a favorable safety profile. CONCLUSIONS:Tenofovir monotherapy is as effective as emtricitabine/tenofovir combination therapy in maintaining long-term viral suppression in patients with a suboptimal response to adefovir, and is well tolerated in this population.
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Authors: Andrea L Cathcart; Henry Lik-Yuen Chan; Neeru Bhardwaj; Yang Liu; Patrick Marcellin; Calvin Q Pan; Maria Buti; Stephanie Cox; Bandita Parhy; Eric Zhou; Ross Martin; Silvia Chang; Lanjia Lin; John F Flaherty; Kathryn M Kitrinos; Anuj Gaggar; Namiki Izumi; Young-Suk Lim Journal: Antimicrob Agents Chemother Date: 2018-09-24 Impact factor: 5.191
Authors: Fabien Zoulim; Jolanta Białkowska-Warzecha; Mircea Mihai Diculescu; Adrian Eugen Goldis; Renate Heyne; Tomasz Mach; Patrick Marcellin; Jörg Petersen; Krzysztof Simon; Soumaya Bendahmane; Isabelle Klauck; Wojciech Wasiak; Harry L A Janssen Journal: Hepatol Int Date: 2016-05-20 Impact factor: 6.047