• Open Access

Efficacy of tenofovir disoproxil fumarate at 240 weeks in patients with chronic hepatitis B with high baseline viral load


  • Potential conflict of interest: The following authors are employees of Gilead Sciences and hold stock interest in the company: Leland Yee, Phillip Dinh, John Flaherty, Kathryn Kitrinos, and Eduardo B. Martins. Jan Sperl and Zahary Krastev have received grants from Gilead. Patrick Marcellin advises, is on the speakers' bureau of, and received grants from Roche, Gilead, Janssen, and MSD. He advises and is on the speakers' bureau of Bristol-Myers Squibb, Novartis, Vertex, Boehringer Ingleheim, Abbott, and Pfizer. Stuart Gordon has received research/grant support from Abbott Laboratories, Bristol-Myers Squibb, Exalenz Bioscience, Gilead Sciences, GlaxoSmithKline, Intercept Pharmaceuticals, Merck & Co., Roche, and Vertex Pharmaceuticals; been a consultant for Achillon Pharmaceuticals, Bristol-Myers Squibb, CVS Caremark, Gilead Sciences, Merck & Co.; served on data monitoring boards for Janssen Pharmaceuticals.

  • Funding for this study was provided by Gilead Sciences, Inc. (Foster City, CA).

  • See Editorial on Page 483


We evaluated the antiviral response of patients with chronic hepatitis B (CHB) who had baseline high viral load (HVL), defined as having hepatitis B virus (HBV) DNA ≥9 log10 copies/mL, after 240 weeks of tenofovir disoproxil fumarate (TDF) treatment. A total of 641 hepatitis B e antigen (HBeAg)-negative and HBeAg-positive patients (129 with HVL) received 48 weeks of TDF 300 mg (HVL n = 82) or adefovir dipivoxil (ADV) 10 mg (HVL n = 47), followed by open-label TDF for an additional 192 weeks. Patients with confirmed HBV DNA ≥400 copies/mL on or after week 72 had the option of adding emtricitabine (FTC). By week 240, 98.3% of HVL and 99.2% of non-HVL patients on treatment achieved HBV DNA <400 copies/mL. Both groups had similar rates of histologic regression between baseline and week 240. Patients with HVL generally took longer to achieve HBV DNA <400 copies/mL than non-HVL patients, but by week 96, the percentages of patients with HBV DNA <400 copies/mL were similar in both groups. Among HVL patients, time to achieving HBV DNA <400 copies/mL was shorter among those initially receiving TDF, compared to ADV. No patient with baseline HVL had persistent viremia at week 240 or amino acid substitutions associated with TDF resistance. Conclusion: CHB patients with HVL can achieve HBV DNA negativity with long-term TDF treatment, although time to HBV DNA <400 copies/mL may be longer, relative to patients with non-HVL. (Hepatology 2013;58:505–513)