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/

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 defici ts 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 neon ates. Methods. Infants less than or equal to 1 month of age with virol ogically confirmed HSV-S SEM disease were eligible for enrollment. Sup pressive oral acyclovir therapy (300 mg/m(2)/dose given either twice d aily or three times per day) was administered for 6 months. Results. T welve (46%) of the 26 infants developed neutropenia (<1000 cells/mm(3) ) while receiving acyclovir. Thirteen (81%) of the 16 infants who rece ived drug 3 times per day experienced no recurrences of skin lesions w hile receiving therapy. In comparison, a previous Collaborative Antivi ral 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 re currence, and an acyclovir-resistant HSV mutant was isolated from anot her patient during the course of the study. Conclusions. Administratio n of oral acyclovir can prevent cutaneous recurrences of HSV after neo natal SEM disease. The effect of such therapy on neurologic outcome mu st be assessed in a larger, Phase III study. As such, additional inves tigation is necessary before routine use of suppressive therapy in thi s population can be recommended.