Background: Letermovir is a novel cytomegalovirus antiviral that is approved for prophylaxis in hematopoietic stem cell transplantation recipients Methods: After obtaining informed consent, letermovir prophylaxis was started in a patient with a presumed late-onset primary, combined T-and B-cell immunodeficiency. Plasma CMV DNAemia was monitored with real-time polymerase chain reaction, and letermovir resistance analyses were performed using Sanger sequencing and Illumina MiSeq next-generation sequencing. Results: A letermovir-resistant cytomegalovirus variant (C325Y mutation in UL56) emerged 17 weeks after start of prophylaxis. The letermovir-resistant variant was able to reactivate without drug selective pressure as this variant was again detected in plasma 20.6 weeks after stopping of letermovir. Conclusions: This case indicates that the C325Y mutation in UL56 does not significantly alter fitness of cytomegalovirus in vivo.

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Keywords letermovir, resistance, viral fitness
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Journal Open Forum Infectious Diseases
Popping, S. (Stephanie), Dalm, V.A.S.H, Lübke, N. (Nadine), Di Cristanziano, V. (Veronica), Kaiser, R, Boucher, C.A.B, & van Kampen, J.J.A. (2019). Emergence and Persistence of Letermovir-Resistant Cytomegalovirus in a Patient with Primary Immunodeficiency. Open Forum Infectious Diseases, 6(9). doi:10.1093/ofid/ofz375