Codex_V5

Emergence of letermovir resistance in a lung transplant recipient with ganciclovir-resistant cytomegalovirus infection.

Abstract: Following a year of valganciclovir prophylaxis, a lung transplant recipient developed cytomegalovirus (CMV) infection that became resistant to ganciclovir, as confirmed by detection of UL97 kinase mutation M460V and a previously uncharacterized UL54 DNA polymerase mutation L516P. The latter mutation is now shown to confer ganciclovir and cidofovir resistance. As predicted from the viral genotype, foscarnet therapy was effective, but resumption of valganciclovir as secondary prophylaxis resulted in a plasma viral load rebound to 3.6 log

Mutant	Gene	Virus	Antiviral	EC50 ratio	Phenotype
D515Y	UL54	Human betaherpesvirus 5	Cidofovir	2.60	Low level resistance
D515Y	UL54	Human betaherpesvirus 5	Foscarnet	1.10	No resistance
D515Y	UL54	Human betaherpesvirus 5	Ganciclovir	3.20	Intermediate level resistance
D981del2	UL54	Human betaherpesvirus 5	Cidofovir	3.20	Intermediate level resistance
D981del2	UL54	Human betaherpesvirus 5	Foscarnet	2.70	Low level resistance
D981del2	UL54	Human betaherpesvirus 5	Ganciclovir	7.00	High level resistance