—Christine. M. Kukka, Project Manager, HBV Advocate
Tenofovir (Viread), one of the leading antiviral drugs for hepatitis B treatment, produced no drug resistance in 585 patients after six years of treatment.
The report, published in the August issue of Hepatology, followed 347 hepatitis B "e" antigen-negative patients and 238 "e" antigen-positive patients who had been treated with the daily antiviral pill for six years.
They examined the molecular make-up of the hepatitis B virus of 52 patients who still had detectable HBV DNA after nearly six years of treatment to see if any of them had developed viral mutations that could "resist" tenofovir's ability to block viral replication.
The researchers reported that failure to take the antiviral as prescribed and natural viral mutations were behind the persistance of detectable viral load in these patients. Those patients were either switched to a combination of tenofovir and emtricitabine or began taking tenofovir as prescribed. To date, all patients have achieved undetecatable viral load.
Abstract:No detectable resistance to tenofovir disoproxil fumarate after 6 years of therapy in patients with chronic hepatitis B.
Kitrinos KM, Corsa A, Liu Y, Flaherty J, Snow-Lampart A, Marcellin P, Borroto-Esoda K, Miller MD. Gilead Sciences, Inc., Foster City, CA, USA.
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 <400 copies/mL at their last study visit regardless of whether they switched to FTC/TDF (n = 34) or maintained TDF monotherapy (n = 17). No patient exhibited persistent viremia (HBV DNA never <400 copies/mL) after week 240.
Conclusion: TDF monotherapy maintains effective suppression of HBV DNA through 288 weeks of treatment with no evidence of TDF resistance. (Hepatology 2013;).
Hepatology. 2013 Aug 12. doi: 10.1002/hep.26686.