Abstract 963 Infectious Diseases Platform, Tuesday, 5/4
From 1989 to 1997, the NIAID CASG evaluated ACV at doses of > 30 mg/kg/day in 88 infants with neonatal HSV disease to assess both safety and efficacy. 79 of the 88 patients had virologically-confirmed HSV disease and were included in both safety and efficacy analyses; 9 of the 88 patients did not have culture-proven HSV infection and were included in only safety analyses. 16 infants received ACV for 21 days at the intermediate-dose of 45 mg/kg/day (ID ACV), and 72 received ACV for 21 days at the high-dose of 60 mg/kg/day (HD ACV). Disease was caused by HSV-1 in 26% of the cases and by HSV-2 in 68% of the cases; the isolate was not typed in 6% of the cases. No patients receiving ID ACV experienced adverse events possibly related to study drug. Of the 72 patients receiving HD ACV, 4 experienced adverse events possibly related to study drug (drug overdose; drug infiltration; neutropenia; and receipt of expired drug). 3 (19%) of 16 patients receiving ID ACV had elevation of creatinine to ≥ 2 mg/dL during therapy, while 2 (3%) of 72 infants receiving HD ACV had similar elevations of creatinine during therapy. With ID ACV, 2 (13%) of 16 patients had an absolute neutrophil count (ANC) of ≤ 1000 during therapy. With HD ACV, 14 (19%) of 72 patients had an ANC ≤ 1000 during therapy. Viral shedding ceased by day 14 in all patients receiving HD ACV; comparison to historical controls revealed that patients receiving ACV at 30 mg/kg/day (standard-dose ACV, or SD ACV) shed virus until day 21. Use of HD ACV decreased mortality at 12 months of age in patients with CNS HSV disease from 14% (SD ACV; n=35) to 4% (HD ACV; n=24). Among infants with disseminated HSV disease, use of HD ACV decreased mortality at 12 months of age from 61% (SD ACV; n=18) to 30% (HD ACV; n=33). Among surviving patients with CNS HSV disease and known follow-up after 12 months, use of HD ACV increased the percentage who were developing normally at 12 months of age from 29% (SD ACV; n=28) to 31% (HD ACV; n=13). Among surviving infants with disseminated HSV disease and known follow-up after 12 months, use of HD ACV increased the percentage who were developing normally at 12 months of age from 60% (SD ACV; n=5) to 79% (HD ACV; n=19). Acyclovir at a dose of 60 mg/kg/day is safe and effective for the treatment of neonatal HSV disease.
Author information
Authors and Affiliations
Consortia
Rights and permissions
About this article
Cite this article
Kimberlin, D., Jacobs, R., Powell, D. et al. The Safety and Efficacy of High-Dose (HD) Acyclovir (ACV) in Neonatal Herpes Simplex Virus (HSV) Infections. Pediatr Res 45, 165 (1999). https://doi.org/10.1203/00006450-199904020-00980
Issue Date:
DOI: https://doi.org/10.1203/00006450-199904020-00980