Emergence of letermovir resistance in solid organ transplant recipients with ganciclovir resistant cytomegalovirus infection: A case series and review of the literature

Ganciclovir (GCV)-resistant cytomegalovirus (CMV) infection is a common problem among solid organ transplant (SOT) recipients without prior CMV immunity (CMV D+/R-). GCV-resistant CMV represents a particular challenge for CMV management. Letermovir is a recently licensed antiviral agent for primary CMV prophylaxis in allogenic hematopoietic stem cell transplant (HSCT) recipients. Given the favorable safety profile and its oral bioavailability letermovir may be considered a valuable off-label option for secondary prophylaxis of GCV-resistant CMV in SOT recipients. Here, we describe our experience with letermovir as secondary prophylaxis for GCV-resistant CMV in two renal transplant recipients and review the literature in regard of previously published cases. Letermovir resistance emerged after a few months of secondary prophylaxis in the two renal transplant recipients. In both cases, the previously described UL56 C325Y letermovir resistance mutation was detected. In vitro studies of letermovir suggest a relatively low genetic barrier to resistance. Therefore, caution is warranted when using letermovir as secondary prophylaxis for GCV-resistant CMV infection.

Automated summary

Letermovir can be considered as a secondary prophylaxis option for GCV-resistant CMV in SOT recipients, but caution is warranted due to the risk of resistance development. Two renal transplant recipients developed letermovir resistance after using it for secondary prophylaxis of GCV-resistant CMV. Letermovir has a relatively low genetic barrier to resistance, highlighting the need for careful consideration when using it for GCV-resistant CMV infection.