TY - JOUR
T1 - Emergence of antiviral resistance during oral valganciclovir treatment of an infant with congenital cytomegalovirus (CMV) infection
AU - Choi, K. Yeon
AU - Sharon, Bazak
AU - Balfour, Henry H
AU - Belani, K.
AU - Pozos, T. C.
AU - Schleiss, Mark R
N1 - 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.).
PY - 2013/8
Y1 - 2013/8
N2 - 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.
AB - 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.
KW - Antiviral therapy
KW - Congenital cytomegalovirus infection
KW - Ganciclovir resistance
KW - UL97 mutation
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U2 - 10.1016/j.jcv.2013.04.004
DO - 10.1016/j.jcv.2013.04.004
M3 - Article
C2 - 23688863
AN - SCOPUS:84879269504
SN - 1386-6532
VL - 57
SP - 356
EP - 360
JO - Journal of Clinical Virology
JF - Journal of Clinical Virology
IS - 4
ER -