Tenofovir Appears Highly Effective as Salvage Therapy for HBV Patients with Suboptimal Response to Adefovir

Variable antiviral effects have been observed in adefovir dipivoxil (ADV) [Hepsera]-treated patients with either wild type or lamivudine [Epivir-HBV] resistant (LAM-R) hepatitis B virus (HBV) infection.

While a HBV DNA decline of >/= 4 log was demonstrated in the majority of patients after 48 weeks of ADV treatment, incomplete suppression of HBV DNA or null response to ADV were also found in large scale studies.

In this study, German researchers examined whether tenofovir disoproxil fumarate (TDF), which has been shown to be highly active against LAM-R HBV infections, is an efficient drug in the treatment of HBV infections with suboptimal ADV responsiveness.

Suboptimal ADV response (HBV DNA decline of less than 3 log or presence of high level viremia greater than 106 log in the absence of an ADV resistant mutants) during ADV treatment was documented in 14 patients with LAM-R chronic HBV infection (mean age 45 years [range25-63]; m/f: 12/2; 13 HBeAg+).

Mean period of ADV administration in these patients was 15 months (range 8-22 months). All 14 patients were directly switched from ADV to TDF at a daily dose of 300 mg.

At this time, mean HBV DNA levels ranged between 5.0 to 7.6 log10 copies/mL (mean 6.6 log10copies/mL) corresponding to a mean HBV DNA decline of HBV DNA -0.9 log10 copies/mL (range -3.4 - +1.9  log10 copies/mL) during the ADV treatment phase.

No patient had decompensated liver cirrhosis but 10 patients had elevated ALT levels. HBV DNA levels were measured on a monthly basis (HBV Monitor, Roche Diagnostics, detection limit 400 copies/ml) over a period of 6-14 months. All patients were screened for resistance-associated mutations within the HBV polymerase gene.

Results

• Following the start of tenofovir treatment, at month 3 and month 6 the mean decrease of HBV DNA was -3.1 log10 copies/mL [range 2.0-4.6] and -3.9 log10 copies/mL [range 1.9-4.6].
• During the observed period, 13 patients reached HBV DNA levels below the detection limit (400 copies/ml) and 5 patients with initially elevated ALT reached normal liver enzymes after a mean duration of 4 months [range 1-9 months] and 6 months [range 1-12 months], respectively.
• Two patients experienced loss of HBeAg after 3 and 5 months.
• At the start of TDF therapy, mutations at rtL180M and rtM204V were shown in 4 of the patients, however without effect on the antiviral response.
• Genotypic ADV resistance was excluded in all patients by direct sequencing of a region spanning the polymerase gene from rt103 to rt244 as previously described.
• No significant side effects were observed.

Conclusion

Because of its high antiviral activity, tenofovir might become a highly effective rescue drug for patients with suboptimal response to adefovir.

11/16/05

Reference
F van Bömmel and others. Tenofovir rescue for patients with lamivudine resistant HBV infection with suboptimal virologic response to adefovir. Abstract 1000. Program and Abstracts of the 56^th annual meeting of the American Association for the Study of Liver Diseases. November 11-15, 2005. San Francisco, CA.