Many aspects of mucocutaneous and visceral HSV infections are amenable to treatment with antiviral chemotherapy.

For mucocutaneous infections acyclovir has been the mainstay of therapy. Several antivirals are available for topical use in HSV eye infections: idoxuridine, trifiuorofhymidine, and topical vidarabine. For HSV encephalitis, intravenous acyclovir is the treatment of choice. For neonatal HSV infections both intravenous vidarabine and acyclovir are effective.

Acyclovir has been shown to be effective in shortening symptoms and the duration of lesions of mucocutaneous HSV infections in immunocompromised patients and first-episode genital herpes in immunocompetent patients. Intravenous and oral acyclovir will also prevent reactivation of HSV in seropositive immunocompromised patients who are undergoing induction chemotherapy for acute leukemia or in the immediate posttransplant period.

Oral acyclovir tablets have also been shown to speed the healing and resolution of symptoms of first and recurrent episodes of genital HSV-1 and HSV-2 infections. The benefit of treating acute episodes of recurrent genital disease with oral acyclovir is modest, and as such, routine use for recurrent episodes of disease, especially for mild episodes, is not recommended. Chronic daily suppressive therapy may be useful in reducing the frequency of reactivation disease among patients with very frequent genital herpes. However, while daily administration of two to five tablets of oral acyclovir for 4 to 6 months appears safe, selective use of the drug must be advocated until there is better understanding of possible long-term toxicity, the frequency with which resistant strains emerge, and the effects of chronic therapy on the transmission of the disease. Chronic suppressive oral acyclovir does not eliminate ganglionic latency, and reactivation of disease occurs after discontinuing therapy. No data are available on the use of oral acyclovir in the treatment of primary or recurrent gingivostomatitis.

Both intravenous vidarabine 15 mg/kg per day over 12 h daily and intravenous acyclovir 30 mg/kg per day given as 10 mg/kg infusion over 1 h at 8-hourly intervals have been shown to be effective in reducing the mortality of HSV encephalitis. Primary determinants of outcome include young age and early therapy. Comparative trials of the two drugs for the treatment of HSV encephalitis have indicated a lower mortality rate and fewer neurologic sequelae with intravenous acyclovir. The major side effect associated with intravenous acyclovir is transient renal insufficiency usually due to crystallization of the compound in the renal parenchyma. This can be avoided if the medication is given slowly over 1 h and the patient is well-hydrated. As CSF levels of acyclovir average only 30 to 50 percent of plasma levels, the dosage of acyclovir used for treatment of CNS infection (30 mg/kg per day) is double that used for treatment of mucocutaneous or visceral disease (15 mg/kg per day). Vidarabine at doses of 15 mg/kg per day tends to produce more hematopoietic and hepatic toxicity than acyclovir, but this is usually not a limiting problem in treating severe neonatal or CNS infections.