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

Abstract

UNLABELLED:

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.

• Authors: Stuart C Gordon, Zahary Krastev, Andrzej Horban, Jörg Petersen, Jan Sperl, Phillip Dinh, Eduardo B Martins, Leland J Yee, John F Flaherty, Kathryn M Kitrinos, Vinod K Rustgi, Patrick Marcellin
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 58 Issue 2 Pg. 505-13 (Aug 2013) ISSN: 1527-3350 [Electronic] United States
• PMID: 23364953 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 American Association for the Study of Liver Diseases.

Chemical References

• 9-(2-((bis(pivaloyloxymethoxy)phosphinoyl)methoxy)propyl)adenine
• Antiviral Agents
• DNA, Viral
• Organophosphonates
• Phosphorous Acids
• Deoxycytidine
• Emtricitabine
• Adenine
• adefovir dipivoxil

Topics

• Adenine (analogs & derivatives, therapeutic use)
• Adult
• Antiviral Agents (therapeutic use)
• DNA, Viral (blood)
• Deoxycytidine (analogs & derivatives, therapeutic use)
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Emtricitabine
• Female
• Hepatitis B virus (genetics)
• Hepatitis B, Chronic (blood, drug therapy)
• Humans
• Longitudinal Studies
• Male
• Middle Aged
• Organophosphonates (therapeutic use)
• Phosphorous Acids (therapeutic use)
• Treatment Outcome
• Viral Load