Letermovir breakthroughs during the French Named Patient Programme: interest of monitoring blood concentration in clinical practice
Letermovir breakthroughs during the French Named Patient Programme: interest of monitoring blood concentration in clinical practice
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DOI：
10.1093/jac/dkaa135
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发表时间：
2020-08-01
影响因子：
5.2
通讯作者：
Hantz, S.
中科院分区：
文献类型：
--
作者：
Alain, S.;Feghoul, L.;Hantz, S.
目的：分析利特莫韦在爱心一级和二级预防中的突破机制。方法：分析由法国国家疱疹病毒参考中心提供的4例法国冠名患者方案患者在体恤一级和二级预防中利特莫韦突破的机制。结果：在3例绝对耐药病例中，2例与治疗中断或血液中低利替莫韦浓度有关。第四例突破与耐药性无关。新一代测序（NGS）基因分型证实，在开始治疗的3个月内，耐药性突变体迅速出现。结论：在替替韦治疗期间，应推荐患者随访时检测替替韦的浓度和基因分型。
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 3months of treatment initiation.Conclusions: Measurement of letermovir concentration and genotyping should be recommended for patient follow-up during letermovir therapy.