No detectable resistance to tenofovir disoproxil fumarate after 6 years of therapy in patients with chronic hepatitis B
Open Access
- 12 August 2013
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hepatology
- Vol. 59 (2), 434-442
- https://doi.org/10.1002/hep.26686
Abstract
One major challenge in the treatment of chronic hepatitis B is to maintain long‐term viral suppression without promoting the selection of drug‐resistant mutations. We analyzed data from 347 hepatitis B e antigen‐negative and 238 hepatitis B e antigen‐positive patients receiving tenofovir disoproxil fumarate (TDF) in an open‐label, long‐term extension of two phase 3 studies. To date, resistance analyses have been completed for patients receiving up to 288 weeks (6 years) of TDF. Population sequencing of hepatitis B virus (HBV) polymerase/reverse transcriptase (pol/RT) was attempted for all patients at baseline, and any patient who remained viremic (HBV DNA ≥400 copies/mL [≥69 IU/mL]) at week 288 or at the end of treatment with TDF (n = 52) or emtricitabine (FTC)/TDF (n = 7). Phenotypic analyses were performed in HepG2 cells using recombinant HBV containing patient pol/RT sequences. Approximately half of the patients on open‐label treatment who qualified for genotyping had pol/RT sequence changes compared to baseline (23/52 [44%] on TDF, 4/7 [57%] on FTC/TDF). Most changes were at polymorphic sites and none were associated with TDF resistance. Virologic breakthrough occurred infrequently and was associated with nonadherence to study medication in the majority of cases (12/16, 75%). Per protocol, 57 patients (10%) were eligible to switch to FTC/TDF; the majority had HBV DNA Conclusion: TDF monotherapy maintains effective suppression of HBV DNA through 288 weeks of treatment with no evidence of TDF resistance. (Hepatology 2014;59:434–442)Keywords
This publication has 25 references indexed in Scilit:
- EASL Clinical Practice Guidelines: Management of chronic hepatitis B virus infectionJournal of Hepatology, 2012
- Management of Chronic Hepatitis B with Nucleoside or Nucleotide Analogues: A Review of Current GuidelinesGut and Liver, 2010
- Chronic hepatitis B: Update 2009Hepatology, 2009
- Hepatitis B virus DNA levels and outcomes in chronic hepatitis BHepatology, 2009
- Clinical outcomes in adults with chronic hepatitis B in association with patient and viral characteristics: A systematic review of evidenceHepatology, 2009
- Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naïve patients is rare through 5 years of therapyHepatology, 2009
- 2-Year GLOBE Trial Results: Telbivudine Is Superior to Lamivudine in Patients With Chronic Hepatitis BGastroenterology, 2009
- Long-term efficacy and safety of adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis BHepatology, 2008
- Long-term Therapy With Adefovir Dipivoxil for HBeAg-Negative Chronic Hepatitis B for up to 5 YearsGastroenterology, 2006
- Long-term safety of lamivudine treatment in patients with chronic hepatitis BGastroenterology, 2003