Administration of oral acyclovir suppressive therapy after neonatal herpes simplex virus disease limited to the skin, eyes and mouth: results of a phase I/II trial

Pediatr Infect Dis J. 1996 Mar;15(3):247-54. doi: 10.1097/00006454-199603000-00014.


Background: Neonatal herpes simplex virus (HSV) infections limited to the skin, eyes and mouth (SEM) can result in neurologic impairment. A direct correlation exists between the development of neurologic deficits and the frequency of cutaneous HSV recurrences. Thus, the National Institutes of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted a Phase I/II trial of oral acyclovir therapy for the suppression of cutaneous recurrences after SEM disease in 26 neonates.

Methods: Infants < or = 1 month of age with virologically confirmed HSV-2 SEM disease were eligible for enrollment. Suppressive oral acyclovir therapy (300 mg/m2/dose given either twice daily or three times per day) was administered for 6 months.

Results: Twelve (46%) of the 26 infants developed neutropenia (< 1000 cells/mm3) while receiving acyclovir. Thirteen (81%) of the 16 infants who received drug 3 times per day experienced no recurrences of skin lesions while receiving therapy. In comparison, a previous Collaborative Antiviral Study Group study found that only 54% of infants have no cutaneous recurrences in the 6 months after resolution of neonatal HSV disease if oral acyclovir suppressive therapy is not initiated. In one infant, HSV DNA was detected in the cerebrospinal fluid during a cutaneous recurrence, and an acyclovir-resistant HSV mutant was isolated from another patient during the course of the study.

Conclusions: Administration of oral acyclovir can prevent cutaneous recurrences of HSV after neonatal SEM disease. The effect of such therapy on neurologic outcome must be assessed in a larger, Phase III study. As such, additional investigation is necessary before routine use of suppressive therapy in this population can be recommended.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acyclovir / pharmacokinetics
  • Acyclovir / therapeutic use*
  • Administration, Oral
  • Antiviral Agents / pharmacokinetics
  • Antiviral Agents / therapeutic use*
  • Drug Resistance
  • Eye Infections, Viral / cerebrospinal fluid
  • Eye Infections, Viral / drug therapy*
  • Eye Infections, Viral / virology
  • Female
  • Herpes Genitalis / cerebrospinal fluid
  • Herpes Genitalis / drug therapy*
  • Herpes Genitalis / virology
  • Herpesvirus 2, Human / drug effects*
  • Herpesvirus 2, Human / genetics
  • Humans
  • Infant, Newborn
  • Male
  • Mouth Diseases / cerebrospinal fluid
  • Mouth Diseases / drug therapy*
  • Mouth Diseases / virology
  • Recurrence
  • Retrospective Studies
  • Skin Diseases, Viral / cerebrospinal fluid
  • Skin Diseases, Viral / drug therapy*
  • Skin Diseases, Viral / virology


  • Antiviral Agents
  • Acyclovir