Improved Neurodevelopmental Outcomes following Long-Term High-Dose Oral Acyclovir Therapy in Infants with Central Nervous System and Disseminated Herpes Simplex Disease

Abstract

Infants with neonatal herpes, classified as central nervous system or disseminated disease, have a high incidence of moderate and severe neurologic deficits despite standard acute therapy. Following completion of parenteral therapy, infants with central nervous system and/or disseminated disease received 2 years of continuous oral acyclovir therapy. Target minimum peak serum acyclovir concentrations were >2 microg/ml for the first three patients, and >3 microg/ml for the subsequent 13 patients. Safety assessments were made every 3 months. We evaluated neurodevelopmental outcomes with Bayley Scales of Infant Development. A total of 16 consecutive herpes simplex virus-infected infants born during 1990 to 2003 received the treatment plan; 13/16 infants had central nervous system disease; 3 had disseminated disease without central nervous system involvement. A total of 69% (11/16) had Bayley scores in the normal range for mental development and 79% (11/14) had motor scores in the normal range. At the final assessment, five children had developmental delays. One child had severe mental delay with normal motor development. Four children had mild mental delays, with severe motor delays in three. All children were independently mobile, without seizure disorder, had normal vision, and had speech development. During the 2-year course of treatment, five children had brief recurrences of dermal lesions, and none had evidence of neurologic deterioration. There were no serious or sustained adverse drug reactions. This pilot study reports improved outcomes in a small cohort of infants with a prolonged course of oral acyclovir. A minority of these children exhibited mild or significant developmental delays. Further investigation of this approach to treatment is warranted.