Oral Acyclovir Suppression and Neurodevelopment after Neonatal Herpes

Abstract

BACKGROUND Poor neurodevelopmental outcomes and recurrences of cutaneous lesions remain unacceptably frequent among survivors of neonatal herpes simplex virus (HSV) disease. METHODS We enrolled neonates with HSV disease in two parallel, identical, double-blind, placebo-controlled studies. Neonates with central nervous system (CNS) involvement were enrolled in one study, and neonates with skin, eye, and mouth involvement only were enrolled in the other. After completing a regimen of 14 to 21 days of parenteral acyclovir, the infants were randomly assigned to immediate acyclovir suppression (300 mg per square meter of body-surface area per dose orally, three times daily for 6 months) or placebo. Cutaneous recurrences were treated with open-label episodic therapy. RESULTS A total of 74 neonates were enrolled — 45 with CNS involvement and 29 with skin, eye, and mouth disease. The Mental Development Index of the Bayley Scales of Infant Development (in which 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 been randomly assigned to acyclovir suppression had significantly higher mean Bayley mental-development scores at 12 months than did infants randomly assigned to placebo (88.24 vs. 68.12, P = 0.046). Overall, there was a trend toward more neutropenia in the acyclovir group than in the placebo group (P = 0.09). CONCLUSIONS Infants surviving neonatal HSV disease with CNS involvement had improved neurodevelopmental outcomes when they received suppressive therapy with oral acyclovir for 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; CASG 103 and CASG 104 ClinicalTrials.gov numbers, NCT00031460 and NCT00031447, respectively.)

Encefalitis herpética neonatal: valor de la clínica versusla biología molecular

“…Dado las características propias del virus herpes se ha planteado la reactivación periódica como causa de mayor deterioro neurológico pero aún el uso de aciclovir oral como terapia supresora, es controversial 19,20 .…”

Genotypic and phenotypic diversity within the neonatal HSV-2 population

“…We utilized samples collected from ten HSV-2-infected neonates enrolled by the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group (CASG) for clinical trials between 1981 and 2008 (8,43,44). These infants encompassed a range of clinical disease manifestations (see Table 1), with about half experiencing invasive CNS disease (5 patients) or disseminated (DISS) disease with CNS involvement (2 patients), and the remainder peer-reviewed) is the author/funder.…”

“…To reveal how genetic variation may contribute to culture phenotype, and ultimately clinical disease manifestations, we sequenced the complete viral genome for all ten neonatal HSV-2 isolates. The clinical trials utilized in this study enrolled HSV-infected infants from multiple enrollment sites across the United States (8,43,44).…”

“…Currently, the antiviral medication acyclovir is the standard therapy for all forms of neonatal HSV disease. Although this intervention has reduced mortality due to invasive disease, most survivors are left with permanent neurodevelopmental deficits (8,9). …”

“…http://dx.doi.org/10.1101/262055 doi: bioRxiv preprint first posted online Feb. 8, 2018; Here we analyzed a set of 10 low-passage HSV-2 isolates collected from neonates with cultureor PCR-confirmed HSV infection, enrolled in three published clinical studies (8,43,44). These samples represented a wide range of clinical manifestations including SEM, CNS, and disseminated disease, and were associated with robust de-identified clinical information.…”