Oral valganciclovir achieved better outcomes than IV ganciclovir for infants with CMV

October 10, 2013

SAN FRANCISCO — Six months of therapy with oral valganciclovir for infants with symptomatic congenital cytomegalovirus disease improved audiologic and neurodevelopmental outcomes, according to data presented here during ID Week.

Cytomegalovirus (CMV)-associated hearing loss can be present at birth or can develop later in childhood. Congenital CMV is also the most frequent viral cause of mental retardation, according to Penelope Dennehy, MD, professor of pediatrics at Brown Medical School and director of the division of pediatric infectious diseases at Hasbro Children’s Hospital, Providence, R.I., who presented the results during the late-breaker session. David W. Kimberlin, MD, from the University of Alabama at Birmingham and course director for the Infectious Diseases in Children Symposium, was lead author of the study.

Although 6 weeks of intravenous (IV) weeks of ganciclovir has been shown to improve long-term hearing outcomes in infants with symptomatic congenital cytomegalovirus (CMV) disease involving the central nervous system (CNS), preliminary results indicate that IV treatment with valganciclovir is superior.

Results of a phase 3, randomized, double-blind, placebo-controlled, multinational study indicate that valganciclovir treatment for 6 months in infants with symptomatic congenital CMV disease improved audiologic and neurodevelopmental outcomes in children to at least 2 years of age. Less neutropenia was also seen during the first 6 weeks of treatment with valganciclovir (19.3%), compared with a previous study of IV ganciclovir (63%). In addition, no excess neutropenia with continuation of valganciclovir treatment was reported from 6 weeks to 6 months compared with placebo.

In the National Institute for Allergy and Infectious Diseases’ Collaborative Antiviral Study Group phase 3 trial, enrolled patients had symptomatic congenital CMV disease with or without CNS involvement lasting 30 days or less. Hearing was assessed at baseline, 6 months, 12 months and 24 months, and neurodevelopment was assessed at 12 months and 24 months by the Bayley Scales of Infant and Toddler Development, Third Edition, according to Dennehy.

Language (P=.0046) and receptive communication (P=.0031) scores were superior at 24 months in the 6-month treatment group compared with the 6-week group. During the first 6 weeks of therapy, 19.3% of subjects experienced grade 3 to 4 neutropenia. From week 6 through month 6, 21.3% of subjects on valganciclovir and 26.5% of subjects on placebo had grade 3 to 4 neutropenia (P=.6353).

One patient had the valganciclovir dose temporarily held due to neutropenia.

“Six months of oral valganciclovir is superior to 6 weeks of therapy with improved hearing outcomes at 12 and 24 months and improved developmental outcomes at 24 months,” Dennehy said during the presentation. “These results apply only to infants with symptomatic congenital CMV disease with and without CNS involvement but do not apply to asymptomatic infection.”

Dennehy added that AST and ALT levels were higher at month 4 of therapy in some patients taking valganciclovir but it did not reach statistical significance.

“However, it does warrant monitoring as longer term valganciclovir is employed widely in the clinical setting,” she said.