Long-term efficacy and safety of emtricitabine plus tenofovir DF vs. tenofovir DF monotherapy in adefovir-experienced chronic hepatitis B patients

• Published in: Journal of hepatology 2014-04, Vol.60 (4), p.715-722
• Main Authors: Berg, Thomas, Zoulim, Fabien, Moeller, Bernd, Trinh, Huy, Marcellin, Patrick, Chan, Sing, Kitrinos, Kathryn M, Dinh, Phillip, Flaherty, John F, McHutchison, John G, Manns, Michael
• Format: Article
• Language: English
• Subjects: Adefovir; Adenine - administration & dosage; Adenine - adverse effects; Adenine - analogs & derivatives; Antiviral Agents - administration & dosage; Antiviral Agents - adverse effects; Combination treatment; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; DNA, Viral - blood; Double-Blind Method; Drug Resistance, Viral; Drug Therapy, Combination; Emtricitabine; Female; Gastroenterology and Hepatology; Hepatitis B; Hepatitis B Antibodies - blood; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - immunology; Hepatitis B, Chronic - virology; Humans; Male; Monotherapy; Mutations; Organophosphonates - administration & dosage; Organophosphonates - adverse effects; Prospective Studies; Resistance; Tenofovir; Treatment Outcome; Viral Load - drug effects; Viremia - drug therapy; Viremia - virology
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2013.11.024

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 (⩾69 IU/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