Comparison of effects of famciclovir and valaciclovir on pathogenesis of herpes simplex virus type 2 in a murine infection model.
The effects of famciclovir (FCV) and valaciclovir (VACV) were compared in a cutaneous infection model for herpes simplex virus type 2 (HSV-2). The compounds were administered orally from day 1 to day 5 postinfection. Both compounds reduced local inflammation and virus replication in the skin. FCV markedly reduced mortality and virus replication in the nervous system. On the cessation of therapy after 5 days, when the levels of infectious virus in the tissues were reduced to below the level of detection, there followed a rebound of virus replication in the ganglia and brain stems of mice that had been treated with VACV. The recurrence of infection in the brain stem occurred on three separate occasions. No such recurrences were observed following FCV treatment. When ganglia were explanted from survivors 6 weeks later, latent virus was shown to be reactivated in all 10 of 10 control, untreated mice. The number of mice whose ganglia yielded virus was reduced to 60% in mice that had been treated with VACV, whereas no mice that had been treated with FCV had evidence of latent infection by this test.
Thackray
A M
AM
Centre for Veterinary Science, Cambridge University Veterinary School, United Kingdom.
Field
H J
HJ
D015075:2-Aminopurine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016475:3T3 Cells / Q000187:drug effects; D000212:Acyclovir / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001933:Brain Stem / Q000821:virology; D004431:Ear, External / Q000821:virology; D000077595:Famciclovir; D005260:Female; D006564:Herpesviridae; D006566:Herpesviridae Infections / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D011355:Prodrugs / Q000494:pharmacology / Q000627:therapeutic use*; D012668:Trigeminal Ganglion / Q000821:virology; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D000998:Antiviral Agents; D011355:Prodrugs; D015075:2-Aminopurine; D014633:Valine; D000077483:Valacyclovir; D000077595:Famciclovir; D000212:Acyclovir