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Anti-HBV Activity of In Vitro Combinations of Tenofovir with Nucleoside Analogs
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Reported by Jules Levin
AASLD, Oct 27-31, 2006, Boston, MA
Y Zhu*, X Qi, W Delaney, M Curtis,
M Miller, and K Borroto-Esoda
Gilead Sciences, Inc., Foster City, CA
Introduction
- Antiviral treatment for CHB is primarily monotherapy which can lead to resistance
- Combination therapy may improve response rates and minimize resistance
- Tenofovir is active against WT and LAMivudine-R HBV
- LAM-R HBV is cross resistant to most other drugs
- Tenofovir DF (approved for HIV) is in phase III trials for CHB
Background
Possible Antiviral Drug Interactions:
- Additivity: Combination activity equals that predicted by the individual activities of the drugs
- Synergy: Combination activity is greater than additive
- Antagonism: Combination activity is less than additive
Analysis and Interpretation of Data
Evaluated with both accepted models for in vitro drug interaction:
- Bliss independence (E(xy) = Ex* Ey)
- MacSynergy II
- Loewe additivity (dx/Dx + dy/Dy = 1)
- Isobologram analysis
OBJECTIVE
- To evaluate the in vitro anti-HBV activity of tenofovir (TFV) combined with:
- Emtricitabine (FTC)
- Lamivudine (3TC)
- Entecavir (ETV)
- Telbivudine (LdT)
Materials & Methods
- AD38 cells which express high levels of HBV
- Combinations tested: TFV plus FTC, 3TC, ETV or LdT
- Antiviral assay:
- Five replicate 96-well plates treated with drug combinations for 4 days
- Extracted intra-cellular HBV DNA quantified with TaqMan PCR assay
- Cytotoxicity assay: cell viability following drug treatments assessed with XTT cleavage as marker
AUTHOR CONCLUSIONS
The combination of tenofovir and emtricitabine resulted in additive to synergistic activity against HBV.
Tenofovir in combination with lamivudine, entecavir or telbivudine produced additive antiviral effects.
These in vitro results support the use of tenofovir in combination therapy of chronic hepatitis B.
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