HIVandHepatitis.com Highlights from the
56th Annual AASLD Conference
 November 11 - 15, 2005 San Francisco, California

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In Comparison to Adefovir, the Efficacy of Tenofovir Seems Unchanged by the Presence of Lamivudine-resistant HBV

The nucleotide analogues adefovir dipivoxil (FDA-approved for the treatment of lamivudine-resistant (LAM-R) hepatitis B virus (HBV) infections) and tenofovir disoproxil fumarate, which is successfully used in the treatment of HIV infections and has also activity against HBV, were recently shown to exhibit marked differences in virological responsiveness after one year of therapy.

In the current study, German researchers compared the long-term effectiveness of tenofovir and adefovir by virological and immunological parameters. In addition, they studied the influence of mutations in the HBV polymerase gene on the virological response.

Eighty-eight HBV infected patients (m/f 72/16, mean age 45 years [18-67]) with chronic hepatitis B were treated either with tenofovir 300mg (n=35, 32 HBe-Ag positive, 24 HBV/HIV co-infected) or adefovir 10mg (n=53, 49 HBe-Ag positive) for a mean duration of 33±7.0 and 24±5.1 months (range 24-48 and 18-34 months) and prospectively analyzed.

At baseline all patients had HBV viremia >20x105 copies/ml (HBV-Monitor, Roche) and elevated ALT.

All patients treated with TDF and 32 patients treated with ADV had genotypic resistance to lamivudine (Epivir-HBV) (70% rt204V, 30% 204I, direct sequencing). ALT, creatinine, and HBV DNA were measured on a three-monthly basis (HBV Monitor, Roche Diagnostics, detection limit 400 copies/ml).

Results

  • During treatment with TDF and ADV, a reduction of HBV DNA below limit of detection was found in 94% and 32% at month 12, in 100% and 35% at month 18 and in 100% and 49% of the patients at month 24 (p<0.00).
  • HBV DNA suppression below 105copies/mL was found in 100% and 54% at month 12 and in 100% and 85% at month 24. HBe-Ag loss was found in 51% and 21% after a mean duration of treatment of 15±9.1 [3-36] and 15±7.4 [5-26] months.
  • HBs-Ag loss was found in 12% (n=4) and 6% (n=3) after a mean duration of treatment of 20±11 [9-34] and 19±9 [6-29] months.
  • No significant side effects were noted in both groups and creatinine levels remained within normal ranges.
  • The patients in the ADV group showed great individual variations of HBV DNA decline.
  • The presence of the LAM-R associated mutations rtM180L and rtM204V at baseline was significantly associated with a lower rate of suppression of
HBV DNA under the limit of detection at month 12 (p=0.01) and 18 (p=0.02) in the  ADV group while HBV DNA levels in the TDF group were not affected.

Based on these results, the authors conclude, “The results of this retrospective analysis demonstrate the higher long-term efficacy and the high safety profile of tenofovir as compared to adefovir.”

“In comparison to adefovir, the efficacy of tenofovir seems not to be influenced by the presence of YMDD mutants.”

11/23/05

Reference
F van Boemmel and others. Long-term effect of tenofovir in the treatment of lamivudine-resistant hepatitis B virus infections in comparison to adefovir. Abstract 184. 56th annual meeting of the American Association for the Study of Liver Diseases (56th AASLD). November 11-15, 2005. San Francisco, CA.