Oral administration of various combined and independent antiviral drug therapies may effectively treat chronic hepatitis B virus (HBV) infection in woodchucks, a well-characterized mammalian model for research with human implications, and provide an alternative strategy for managing drug resistance.
The researchers from Cornell University, Ithaca, New York; Gilead Sciences, Durham, North Carolina; and Georgetown University Medical Center, Washington, DC report their findings in the October 2008 issue of the journal Antimicrobial Agents and Chemotherapy.
Chronic infection with HBV is responsible for 1.2 million annual deaths worldwide. Statistics also show that 2 billion people currently or previously suffered from infection while 350 million people are chronic carriers of HBV and are at risk of developing chronic hepatitis, hepatic cirrhosis, and hepatocellular carcinoma. Preventative vaccines are currently offered, however, side effects and drug resistance are limiting the efficacy of available treatment therapies.
In the study researchers evaluated the antiviral effects of orally administered adefovir dipivoxil (ADV) or tenofovir disoproxil fumarate (TDF) alone or in combination with lamivudine (3TC) or emtricitabine (FTC) in woodchucks with chronic hepatitis virus infection. Initial results showed once daily treatment for 48 weeks with ADV plus 3TC or TDF plus FTC greatly reduced viral levels from those pretreatment. Additional treatment with TDF plus 3TC, ADV alone, ADV plus FTC, TDF alone, 3TC alone, and FTC alone showed pronounced declines in viral levels in all groups. Following drug withdrawal most woodchucks displayed renewed hepatitis virus replication, but some did experience sustained effects. Lastly, no toxicity was observed following administration of any of the drugs or drug combinations.
"In conclusion, the oral administration of 3TC, FTC, ADV, and TDF alone and in combination was safe and effective in the woodchuck model of HBV infection," say the researchers.
- S. Menne, S.D. Bulter, A.L. George, I.A. Tochkov, Y. Zhu, S. Xiong, J.L. Gerin, P.J. Cote, B.C. Tennant. Antiviral Effects of Lamivudine, Emtricitabine, Adefovir Dipivoxil, and Tenofovir Disoproxil Fumarate Administered Orally Alone and in Combination to Woodchucks with Chronic Woodchuck Hepatitis Virus Infection. Antimicrobial Agents and Chemotherapy, 2008; 52 (10): 3617 DOI: 10.1128/AAC.00654-08
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