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.