Understanding antiviral intolerance in the management of cytomegalovirus; a scoping review

Older antiviral agents for managing cytomegalovirus (CMV) infections post transplantation are associated with treatment limiting toxicities. Presently, there is no consensus on the definition of 'antiviral intolerance' however for the purposes of this systematic scoping review, it was defined as a Type A adverse drug reaction leading to cessation or dose modification. The literature was evaluated to improve clinician understanding to the extent and impact of antiviral intolerance when managing CMV infection post transplantation.

In the 71 studies evaluated, intolerance to CMV antivirals (161 instances) were identified as hematological toxicities (44%), predominantly neutropenia (grade 3 to 4), leukopenia, and thrombocytopenia, acute kidney injury (AKI) (20%), and gastrointestinal intolerances (12%). Granulocyte colony stimulating factor was used for neutropenia or leukopenia in 43% of instances. Maribavir and letermovir were identified in fewer studies ( n  = 16). Dose reductions were reported as a management strategy in 15% of intolerances. Severity and supportive management of intolerances were poorly characterized.

The most commonly identified intolerances were acute kidney injury, hematological and gastrointestinal effects in older anti-CMV agents. Fewer studies described intolerance of the newer agents. Detailed descriptions of intolerances are absent within the literature and there is an opportunity to standardize terminology used to help guide clinical practice.