Alain S, et al. J Antimicrob Chemother 2020.
OBJECTIVES: To analyse mechanisms of letermovir breakthrough during compassionate primary and secondary prophylaxis.
METHODS: Mechanisms of letermovir breakthrough during compassionate primary and secondary prophylaxis were analysed in four patients from the French Named Patient Programme by the French National Reference Centre for Herpesviruses.
RESULTS: Of three absolute resistance cases, two were associated with treatment interruption or low letermovir concentrations in blood. A fourth case of breakthrough was not associated with resistance. Next-generation sequencing (NGS) genotyping confirmed rapid emergence of resistant mutants, within 3 months of treatment initiation.
CONCLUSIONS: Measurement of letermovir concentration and genotyping should be recommended for patient follow-up during letermovir therapy.