Emergence of antiviral resistance during oral valganciclovir treatment of an infant with congenital cytomegalovirus (CMV) infection

K. Yeon Choi, Bazak Sharon, Henry H Balfour, K. Belani, T. C. Pozos, Mark R Schleiss

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Congenital infection with human cytomegalovirus (CMV) is a major cause of morbidity, including sensorineural hearing loss (SNHL), in newborns. Antiviral therapy with ganciclovir (GCV) and its oral prodrug, valganciclovir (VAL-GCV) are increasingly being administered to infected infants, toward the goal of improving neurodevelopmental and auditory outcomes. In this case report, we describe a symptomatic congenitally infected infant treated with VAL-GCV in whom GCV resistance was suspected, based on a 50-fold increase in viral load after 6 weeks of oral therapy. Analyses of CMV sequences from both blood and urine demonstrated populations of viruses with M460V and L595F mutations in the UL97 phosphotransferase gene. In contrast, analysis of viral DNA retrieved from the newborn dried blood spot demonstrated wild-type UL97 sequences. DNAemia resolved after the discontinuation of VAL-GCV. Long-term VAL-GCV therapy in congenitally infected infants can select for resistant viral variants, and anticipatory virological monitoring may be warranted.

Original languageEnglish (US)
Pages (from-to)356-360
Number of pages5
JournalJournal of Clinical Virology
Volume57
Issue number4
DOIs
StatePublished - Aug 2013

Bibliographical note

Funding Information:
Grant support from NIH HD044064 and 038416 is acknowledged (M.R.S.). These studies were also supported by an Amplatz Children's Discovery award (B.Z.).

Keywords

  • Antiviral therapy
  • Congenital cytomegalovirus infection
  • Ganciclovir resistance
  • UL97 mutation

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