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. 2020 Aug 1;75(8):2253-2257.
doi: 10.1093/jac/dkaa135.

Letermovir breakthroughs during the French Named Patient Programme: interest of monitoring blood concentration in clinical practice

S Alain  1   2   3 , L Feghoul  4 , S Girault  5 , Q Lepiller  6 , E Frobert  7 , D Michonneau  8 , A Berceanu  9 , S Ducastelle-Lepretre  10 , V Tilloy  2   3 , E Guerin  3 , J Le Goff  4 , G Peytavin  11 , S Hantz  1   2
Affiliations

Letermovir breakthroughs during the French Named Patient Programme: interest of monitoring blood concentration in clinical practice

S Alain et al. J Antimicrob Chemother. .

Abstract

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.

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