Of the large number of agents under development for the treatment of herpes
virus infections [herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV)], only ten have apparently reached clinical development.
Aciclovir was approved for the treatment of HSV
infections over 10 years ago, and it remains an important and reliable
antiviral agent. Recent approvals in some countries of
valaciclovir for VZV
infection and
famciclovir for both HSV and VZV
infections demonstrate the rapidity of change in this field. Intravenous
ganciclovir and
foscarnet are approved for the treatment of CMV
infection in the immunocompromised patient. Five of the antiherpetic drugs under current clinical development are
nucleoside analogues or their
prodrugs; another is a phosphorylated
nucleoside (
nucleotide). Four of the
nucleoside agents-
penciclovir,
famciclovir,
valaciclovir and
lobucavir-are being developed for the management of HSV and VZV
infections.
Valaciclovir is also being developed for the prevention of CMV
infections and
famciclovir and
lobucavir for the treatment of
hepatitis B virus infection. Oral
ganciclovir,
lobucavir,
ISIS 2922 and
cidofovir are being developed for the suppression of CMV
infections in immunocompromised patients.
Sorivudine has been studied in VZV
infections. n-
Docosanol is under development for HSV
infections, and
cidofovir is being developed for both HSV and CMV
infections, as well as for treatment of other
viral diseases. Traditionally, the adverse effects associated with anti-CMV compounds have been more difficult to manage and are acceptable clinically only because of the severity of the underlying
infection and lack of safer therapeutic alternatives. In general, toxicity issues continue to be problematic in the anti-CMV arena, although newer agents have improved the situation to some extent. In contrast, the safety of anti-HSV compounds has traditionally been excellent, establishing a safety standard that must be met by newer agents entering the field.