Cytomegalovirus (CMV) manifestations remain important complications after allogeneic hematopoietic stem cell transplantation (HSCT), even in the current era. Unfortunately, available anti-CMV agents, mainly viral polymerase inhibitors, have a substantial risk of myelosuppression and nephrotoxicity. Letermovir, a novel anti-CMV drug that targets the viral terminase complex, has recently been approved for the prevention of clinically significant CMV infection in adult CMV seropositive hematopoietic stem cell transplantation recipients. This molecule could become a paradigm-shifting drug in preventing CMV manifestations based on its novel mechanism of action, lack of cross-resistance with available drugs, proven efficacy in a large randomized clinical trial, and its beneficial toxicity and tolerability profile. Drug-drug interactions and the lack of any activity against other viruses are the main shortcomings of letermovir.
Keywords: antiviral; antiviral resistance; cytomegalovirus; letermovir; pre-emptive; prophylaxis; terminase complex.