AASLD-No Hepatitis B Virus Resistance to Tenofovir Seen Out to 5 Years

No Hepatitis B Virus Resistance to Tenofovir Seen Out to 5 Years:

Presented at AASLD

By Bob Roehr

SAN FRANCISCO -- November 11, 2011 -- Hepatitis B virus (HBV) showed no resistance to tenofovir disoproxil fumarate (TDF) up to 5 years, according to a study presented here at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).
Patrick Marcellin, MD, PhD, Hospital Beaujon, University of Paris, Clichy, France, presented interim 5-year data on the planned 8-year open-label follow-up study of TDF on November 8.
The initial studies randomised HBeAg-negative and -positive patients 2:1 to receive TDF or adefovir dipivoxil (ADV) for 48 weeks followed by open-label TDF. At the physician’s discretion, after week 72, patients with HBV DNA more then 400 copies/mL could add emtricitabine (FTC) as a fixed-dose combination tablet.

Genetic sequencing of HBV pol reverse transcriptase was done on baseline samples, at time of breakthrough (defined as either more then 1 log10 from nadir or HBV DNA more then 400 copies/mL after less then 400 copies/mL), at week 240, and at time of study discontinuation or FTC addition.
Retention rates were 81% and 70% in the studies at 5 years, with 83% of patients at less then 400 copies/mL HBV DNA, said Dr. Marcellin.

Only 4 of 494 (0.8%) patients were classified as having virologic breakthrough during year 5 of the study, and 3 of those had documented nonadherence during the time of breakthrough, where TDF plasma levels were undetectable. However, on resumption of treatment, all 4 patients suppressed their viraemia less then 400 copies/mL.
No patients showed persistent viraemia in year 5. Of the 12 patients who did experience viraemia more then 400 copies/mL, 6 were on TDF and 6 were on the TDF/FTC combination. Their levels of viraemia were sufficiently high for genetic analysis, and all of the polymorphic site changes were unique.

Dr. Marcellin concluded, ôDuring the fifth year, of the almost 500 patients [77% of the initial cohort], virologic breakthrough was rare, transient, and associated with documented nonadherence.

Ishak fibrosis scores also improved over baseline. In year 1, 30% of patients showed a worsening of fibrosis, whereas 60% reported no change. By year 3, only 2% showed a worsening, 30% showed no change, and nearly 70% showed improvement. By year 6, no patient scores were worsening, 30% showed no change, and nearly 70% continued to show improvement.

[Presentation title: No Detectable Resistance to Tenofovir Disoproxil Fumarate (TDF) Following up to 240 Weeks of Treatment in Patients With HBeAg+ and HBeAg- Chronic Hepatitis B Virus Infection. Abstract 238]