The outcomes of neonatal herpes simplex virus (HSV) disease are dependent on the extent of the disease. Approximately 30% of babies with disseminated disease die, but only 20% of survivors have neurological sequelae. In contrast, only 6% of babies with CNS disease die, but approximately 70% have permanent neurological impairment. Antiviral suppressive therapy prevents the recurrence of localised disease in patients with genital or orolabial HSV infection. The National Institute of Allergy and Infectious Diseases (NIAID) Collaborative Antiviral Study Group (CASG) conducted parallel, identical, phase III, placebo-controlled studies of oral acyclovir suppressive therapy after neonatal HSV disease to determine the efficacy and safety of long-term antiviral administration during infancy.

One study involved neonates with CNS involvement (n= 45) and the other enrolled neonates with skin, eye, and mouth involvement (n= 29). After completing 14 to 21 days of parenteral acyclovir, they were randomised to immediate acyclovir suppression 300 mg/m2 per dose orally, three times daily for 6 months or placebo. Cutaneous recurrences were treated with open-label episodic therapy.

The Mental Development Index of the Bayley Scales of Infant Development (scores range from 50 to 150, with a mean of 100 and with higher scores indicating better neurodevelopmental outcomes) was assessed in 28 of the 45 infants with CNS involvement (62%) at 12 months of age.

After adjustment for covariates, infants with CNS involvement who had received aciclovir suppression had statistically significantly higher mean Bayley mental-development scores at 12 months than those in the placebo group (88.24 vs. 68.12, p = 0.046). There was however a trend toward more neutropenia in the aciclovir group than in the placebo group (p = 0.09).

The researchers conclude from these findings that infants surviving neonatal HSV disease with CNS involvement had improved neurodevelopmental outcomes when they received suppressive therapy with oral aciclovir for 6 months. They note that therapeutic studies of rare diseases such as neonatal herpes present unique challenges. Each of the previous major investigations of the management of neonatal HSV conducted by the CASG has spanned the course of a decade; the current studies were no exception, requiring 11 years to enroll 74 infants.

According to an accompanying editorial, this study presents a practical approach to preventing further CNS damage and decreasing the transmission of HSV from infected babies after the initial treatment with parenteral acyclovir. It notes that the number of patients was small and the statistical analysis was somewhat limited, not only by the loss of patients to follow-up but also by the fact that infants in the placebo group who had two recurrences were treated with open-label acyclovir. However it concludes that extended oral acyclovir therapy should improve the lives of babies who have survived neonatal HSV. It is hoped that specific antiviral therapy will be joined by the active immunisation to prevent maternal HSV infections.