Table 3. Clinical scenarios in which monitoring of CMV-specific T-cell-mediated immune response has been evaluated, and suggestions for future studies.

Clinical scenario	Predicted event	Previous studies	Monitoring method	Proposed intervention
High-risk patients (D+/R−, T-cell-depleting antibodies, lung transplantation) during antiviral prophylaxis	Late-onset diseasea	Yes103, 107, 108, 137	QuantiFERON-CMV, ELISpot	Prolong antiviral prophylaxis or close monitoring for viremia if inadequate response
High-risk patients (D+/R−) after discontinuing antiviral prophylaxis	Late-onset diseasea	Yes105	QuantiFERON-CMV	Prolong antiviral prophylaxis or close monitoring for viremia if inadequate response
High-risk patients (T-cell-depleting antibodies, lung or pancreas transplantation) after discontinuing antiviral prophylaxis	Late-onset diseasea	No		Prolong antiviral prophylaxis or close monitoring for viremia if inadequate response
Pre-transplant assessment in intermediate-risk patients (R+ with no other factors)	Post-transplant viremia and/or disease	Yes104, 108	QuantiFERON-CMV, ELISpot	Initiate antiviral prophylaxis in patients with inadequate response
Intermediate-risk patients (R+) on preemptive therapy with no concurrent viremia	Subsequent viremia and/or disease	Yes108, 109, 110, 112, 113, 138	ICS, QuantiFERON-CMV, ELISpot, MHC-tetramer staining	Reduce the frequency and/or discontinue monitoring of viremia if adequate response
Intermediate-risk patients (R+) on preemptive therapy with asymptomatic viremia	Spontaneous clearance	Yes106	QuantiFERON-CMV	Withhold antiviral therapy if adequate response
Active CMV infection or disease during antiviral treatment	Response to antiviral treatment	No		Decrease immunosuppression and/or modify antivirals if inadequate response
Active CMV infection or disease after discontinuation of antiviral treatment	Post-treatment relapse	Yes115	ICS	Initiate secondary prophylaxis if inadequate response
Acute graft rejection treated with steroid boluses and/or T-cell-depleting antibodies	Disease following anti-rejection therapy	No		Initiate prophylaxis if inadequate response

Abbreviations: CMV, cytomegalovirus; ELISpot, enzyme-linked immunosorbent spot assay; ICS, Intracellular cytokine staining; MHC, major histocompatibility complex.

^aRefers to the occurrence of CMV disease after discontinuing antiviral prophylaxis with ganciclovir or valganciclovir (usually administered for 100–200 days).