Abstract
BACKGROUND: Cytomegalovirus (CMV) infection is a common opportunistic infection associated with significant morbidity, mortality, and risk of allograft loss. Early detection of viremia and initiation of treatment prior to disease progression is paramount. Alternatively, in the absence of treatment, many patients also control CMV infection, including low-level viremia, without progressing to disease. Thus, many treatment decisions (e.g., viremia thresholds to initiate treatment) are not currently well-defined. Given the excessive toxicities and costs of antiviral therapy, there is growing interest in assays that measure CMV-specific T-cell immunity (TCI), which may predict protection against infection. The Viracor® CMV T-cell Immunity Panel (CMV-TCIP) uses flow cytometry and intracellular cytokine staining (ICS) to measure % of CMV-specific CD4+ and CD8+ T-cells. Other currently available TCI commercial assays measure only aggregate (CD4+ and CD8+) or CD8+ immune responses only. METHODS: We included patients who had CMV-TCIP results at Rhode Island Hospital (January 2016–February 2018) and who subsequently had at least one additional assessment for CMV viremia. CMV events were defined as rising viremia prompting initiation of treatment and were captured after the most recent CMV-TCIP result. We built CMV-protection relative-operating curves (ROC) for % of CD4+ and CD8+ CMV-specific T-cells. RESULTS: We analyzed 17 samples from 13 patients: 10 were SOT (eight kidney, two heart) recipients (seven CMV R+, three D+/R−); two had hematologic malignancies; one other was immunosuppressed (prednisone, infliximab) for autoimmune colitis. Four additional samples were excluded because of CD4+ or CD8+ ICS background positivity. The CMV-protection ROC AUC was significant for % of CMV-specific CD4+ but not CD8+ T-cells (Figure 1). At a cut-off of 0.26% CMV-specific CD4+ T-cells, PPV was 90% (95% CI 71–100%), and NPV was 86% (95% CI 60–100%). In 14 of 17 cases (82%), the CMV-TCIP result was useful in guiding management. CONCLUSION: In this small, single-center, heterogeneous series, the % of CMV-specific CD4+ T-cells measured by ICS was predictive of protection against CMV. The CMV-TCIP can be a useful, cost-effective test, and merits further validation in larger prospective studies. Figure 1. DISCLOSURES: D. Farmakiotis, Viracor: Consultant and Invited speaker, Consulting fee.