Postexposure treatment of experimental DHBV infection: a new therapeutic strategy.
The therapeutic efficacy of antiviral agents for postexposure prophylaxis to hepadnavirus infection has been studied using acyclovir and foscarnet in the duck hepatitis B virus (DHBV) model. A total of 112 Pekin-Aylesbury ducks were inoculated with DHBV at 11 days post-hatch. Three days later, groups of these birds were injected intraperitoneally twice daily for 10 days with acyclovir (25 mg/kg) or foscarnet (250 mg/kg) or phosphate-buffered saline. Serum samples were taken before, during, and up to 4 weeks post-treatment and were analysed for DHBV DNA by dot hybridization. Liver tissue obtained at sacrifice was examined for viral DNA and for histological changes. At completion of treatment with acyclovir, 21 of 22 ducks were not viremic, compared with 6 of 26 control birds (P less than 0.001). Four weeks after withdrawal of acyclovir, 12 of 20 ducks remained nonviremic, compared with 2 of 23 controls (P less than 0.01). In liver tissue, viral DNA was detected in 10 of 19 treated ducks, compared with 21/24 controls (P less than 0.01). Histological changes of hepatitis were present in more of the control birds than in the treated group. The results with foscarnet treatment were similar, although a smaller inoculum of DHBV was used and fewer control birds became infected. The administration of antiviral agents soon after exposure prevented productive infection in approximately 50% of birds. Therefore, the use of a safe antiviral agent such as acyclovir, which can be given orally, should be considered in post-exposure prophylaxis against human hepatitis B virus (HBV) infection.
Freiman
J S
JS
Department of Infectious Diseases, University of Sydney, NSW, Australia.
Murray
S M
SM
Vickery
K
K
Lim
D
D
Cossart
Y E
YE
D000212:Acyclovir / Q000627:therapeutic use*; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000032:analysis; D004372:Ducks; D005260:Female; D017245:Foscarnet; D015611:Hepatitis B Virus, Duck / Q000187:drug effects* / Q000235:genetics; D006524:Hepatitis, Viral, Animal / Q000188:drug therapy*; D008297:Male; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000998:Antiviral Agents; D004279:DNA, Viral; D017245:Foscarnet; D010746:Phosphonoacetic Acid; D000212:Acyclovir