Cytomegalovirus (CMV) causes significant morbidity after solid organ transplantation (SOT). CMV-seronegative recipients of organs from seropositive donors (D+R-) are at highest risk despite antiviral prophylaxis. Moreover, prolonged antiviral prophylaxis is associated with significant cost and toxicity. Ideally, an optimized risk stratification of D+/R- SOT recipients would individualize the duration of prophylaxis. We hypothesized that development of an interferon-gamma (IFN-γ) response to CMV is protective against CMV disease, and could guide prophylaxis.
After obtaining consent, blood samples were collected at baseline within 1 week after SOT, then monthly thereafter for 6 months. CMV-specific immunity was assessed using the Quantiferon-CMV (QFT-CMV) IFN- γ release assay (IGRA). Patients were followed for up to 12 months post-transplant.
Twenty subjects completed all measurements, 13 (65%) were male; median age of 60 years. The transplanted organs included: 9 (45%) kidneys, 7 (35%) livers, 1 (5%) heart, 1 (5%) lung, 1 (5%) heart/liver and 1 (5%) pancreas. Induction immunosuppression consisted of antithymocyte globulin in 5 (25%) patients, methylprednisolone in 12 (60%), basiliximab in 5 (25%), alemtuzumab in 3 (15%) and azathioprine in 1 (5%). Most were on maintenance immunosuppression with tacrolimus, mycophenolate and prednisone; all received antiviral prophylaxis, except 3 liver recipients who were monitored for CMV and received preemptive therapy.
Using the suggested cut off of 0.2 IU/mL, all patients were negative at baseline; by months 3 and 6, 3 (15%) and 7 (35%) patients were positive by the QFT-CMV. CMV disease occurred in 6 (30%) patients, of which 3 were no longer on prophylaxis. All had negative QFT-CMV results prior to diagnosis; QFT-CMV testing after infection was available in 5/6 patients, and all tested positive; none had relapsed.
An IFN- γ response to CMV may be acquired even during antiviral prophylaxis. Patients reactive by the QFT-CMV assay were protected from disease. Conversely, non-reactive patients remain at risk for CMV. QFT-CMV may be beneficial in identifying D+/R- SOT recipients who remain at high risk for CMV disease, and may benefit from continued prophylaxis.
L. Misner, None
E. Beito, None
E. Theel, None
R. R. Razonable, None