Beyond Thresholds: CMV Replication Kinetics as Early Predictors of Clinical Risk in Transplant Recipients

Cytomegalovirus (CMV) is a pervasive beta herpes virus which establishes latency after primary infection. CMV infection after solid organ transplant is common and associated with negative outcomes for both the allograft and patient. The medications that are available can be associated with significant toxicity and do not provide a cure. Reliable protection from recurrence and freedom from antiviral therapy requires development of CMV-specific cell-mediated immunity (CMI). This can be difficult to achieve after transplant in the setting of immunosuppressive medications due to the complexity of the immune response required to control the virus and often leads to prolonged antiviral courses and lengthy monitoring periods. While assays exist to measure CMI, they are not widely available and can pose challenges related to cost and collection restrictions. Conversely, viral replication trends utilizing widely available molecular diagnostics in tandem with risk factor assessment can be used as surrogate markers for the presence and development of CMI which can guide need for antiviral prophylaxis or treatment. The purpose of this review is to establish a foundation for the immunology of CMV and widely used molecular diagnostics, highlight CMV-specific CMI testing as an emerging molecular diagnostic tool, justify how the currently available antiviral drugs have limitations in their utility and outline the opportunity to use viral replication and replication kinetics, rather than absolute viral load thresholds, as a tool to understand the complex interplay of the host's immune response and the virus' capacity for replication while guiding clinical decision making.