• Participants With Neurologic Impairment at 12 Months as Measured by a Bayley's Neuro-developmental Assessment.(Motor Scores) [ Time Frame: At 12 months of life. ] [ Designated as safety issue: No ]
  Motor scores of all participants completing 6 months of blinded therapy as measured by the Bayleys neuro-developmental assessment at 12 months. Scores are classified as the following: greater than or equal to 115 suggests accelerated performance; 85 - 114 suggests development within normal limits; 70 - 84 suggests mildly delayed development and less than or equal to 69 suggests significant delayed development.
  
  
• Participants With Neurologic Impairment at 12 Months as Measured by a Bayley's Neuro-developmental Assessment.(Mental Scores) [ Time Frame: At 12 months of life. ] [ Designated as safety issue: No ]
  Mental scores of all participants completing 6 months of blinded therapy as measured by the Bayleys neuro-developmental assessment at 12 months. Scores are classified as the following: less than or equal to 115 suggests accelerated performance; 85 - 114 suggests development within normal limits; 70 - 84 suggests mildly delayed development and less than or equal to 69 suggests significant delayed development.
  
  

• Detection of Herpes Simplex Virus (HSV) DNA in the Cerebrospinal Fluid (CSF) by Polymerase Chain Reaction (PCR) at Anytime During the Initial 12 Months of Life. [ Time Frame: post randomization at 12 months ] [ Designated as safety issue: No ]
  Number of participants with positive herpes simplex virus (HSV) DNA by polymerase cahin reaction (PCR) in the cerebrospinal fluid of subjects assessed during the initial 12 months of life.
  
  
• Two or Fewer Episodes of Cutaneous Recurrence of HSV Disease Post-randomization During the Initial 12 Months of Life. [ Time Frame: post randomization - 12 months ] [ Designated as safety issue: No ]
  Number of participants experiencing 2 or fewer HSV recurrences during the first 12 months of life as measured by assessments and reports at study visits.
  
  

Neonatal herpes simplex virus (HSV) disease complicates approximately one in every 3,000 births in the United States. This study will be a placebo-controlled Phase III evaluation of suppressive therapy with oral Acyclovir suspension following neonatal HSV infections limited to the skin, eyes, and mouth (SEM). This study will evaluate the efficacy of long-term suppressive therapy with oral acyclovir in infants with SEM disease. It will determine if suppressive oral acyclovir therapy improves neurological outcome in infants following SEM disease. Only infants with SEM disease will qualify for this study. After qualifying for the study and obtaining informed consent, the infant will complete 14 days of intravenous (IV) Acyclovir (20 mg/kg/dose given every 8 hours). Patients will be randomized to receive suppressive oral Acyclovir versus placebo only if they continue to meet all study inclusion criteria at the completion of the IV therapy. This study will be double-blinded and placebo controlled. At the time of randomization, the patient will be placed in 1 of 2 groups (oral suppressive Acyclovir versus placebo). If a patient in either group has a cutaneous HSV recurrence, open-label oral Acyclovir (80 mg/kg/day divided into 4 doses per day) will be provided for 5 days. During the time of administration of open-label oral Acyclovir, study drug will be withheld. All children will be followed at 6, 12, 24, 36, 48, and 60 months of age. Physical examination, hearing assessment, and retinal examination will be performed at each follow up visit. Standardized neurologic evaluation will be performed at 12, 24, 36, 48, and 60 months of age.