Tenofovir Suppresses HBV in Patients Non-responsive to Adefovir, But Not in Those with Adefovir-resistant HBV

The nucleotide analogue adefovir (Hepsera) results in primary non-response in as many as 50% of patients with chronic Hepatitis B, according to researchers at the University of Michigan. Tenofovir (Viread), another nucleotide analogue that is closely related to adefovir, may result in more potent and durable HBV suppression, as it is administered at a dose 30 times that of adefovir.

The objective of the current study presented at DDW 2007 was to determine viral response to tenofovir or tenofovir + emtricitabine (FTC; Emtriva) therapy in 11 patients with suboptimal response to adefovir. Both tenofovir and emtricitabine are approved for treatment of HIV, and are components of the Truvada fixed-dose combination pill.

Patients with suboptimal virological response to adefovir (HBV DNA > 4 log₁₀ copies/mL after > 6 months of treatment) were switched to tenofovir (n=9) or tenofovir + emtricitabine (n=2). At the start of tenofovir therapy, the median age was 51 years and 9 patients were HBeAg positive.

HBV DNA by PCR and liver chemistries were monitored every 3-6 months. Viral resistant mutations were determined using direct sequencing. Cloning of serial samples was performed for pts with known adefovir-resistance and pts with a suboptimal virological response to tenofovir.

Results

• 2 patients had viral breakthrough and genotypic resistance (rtA181V) to adefovir.
  
  
• Patient #1 had an initial decrease in HBV DNA from 7.6 to 5.1 log¹⁰ copies/mL after 3 months of tenofovir, HBV DNA levels then plateaued for the next 11 months and then decreased to 3.7 log₁₀ c/mL, 4 months after the addition of emtricitabine.
  
  
• The percentage of clones with rtA181V and rtN236T mutations was 100% and 3% at the start of tenofovir and 100% and 8% after 13 months of tenofovir.
  
  
• Patient #2 had decrease in HBV DNA from 7.3 log₁₀ to 2.6 log₁₀ copies/mL after 9 months of tenofovir + emtricitabine.
  
  
• The percentage of clones bearing the rtA181V mutants was 100% at the start of tenofovir and 96 % after 3 months of tenofovir; rtN236T was not detected in any of the clones.
  
  
• Nine patients did not have adefovir-resistant mutations, and median HBV DNA at the start of tenofovir was 6.8 log₁₀ copies/mL.
  
  
• After a median 13 months on tenofovir, 6 had undetectable HBV DNA, 2 had HBV DNA of 2.5 log₁₀ copies/mL.
  
  
• The remaining patient had suboptimal virological response on tenofovir, with HBV DNA decreasing from 7.6 to 5.1 log₁₀ copies/mL after 21 months of treatment.
  
  
• None of the clones had any adefovir-resistant mutations at baseline, but 17% of the clones had rtA181T mutation at the last visit.

Conclusion

Based on these findings, the investigators concluded, “tenofovir is effective in suppressing HBV replication in most patients with suboptimal response to adefovir. However, tenofovir alone may be less effective in patients with adefovir resistance, as adefovir-resistant mutations persist and are further selected. Our data suggest that mutations resistant to adefovir are cross-resistant to tenofovir.”

05/22/07

Reference
J Tan, S N Wong, M T Hussain, and others. Tenofovir (TDF) monotherapy is effective in suppressing serum HBV DNA in chronic hepatitis B (CHB) patients with primary nonresponse to adefovir (ADV) but not those with ADV-resistant HBV. Digestive Disease Week 2007 (DDW 2007). Washington, DC. May 19-24, 2007. Abstract 95.

Return to to DDW 2007 Main Page