A Randomized Study of Quantiferon CMV-directed Versus Fixed-duration Valganciclovir Prophylaxis to Reduce Late CMV After Lung Transplantation

Abstract

Background. We provide the results of the first interventional study of cytomegalovirus (CMV)-specific immune monitoring to direct the length of antiviral prophylaxis in lung transplantation (LTx). Methods. Patients (n = 118) at risk of CMV infection were randomized 1:2 to either 5 months or variable length valganciclovir prophylaxis (5–11 mo post-LTx), as determined by the QuantiFERON (QFN)-CMV assay. Patients with a negative QFN-CMV assay (< 0.2 IU/mL) received prolonged valganciclovir prophylaxis. Results. The primary endpoint that was the incidence of CMV infection in the lung allograft within 18 months of LTx was significantly reduced in the QFN-CMV directed arm (37% versus 58%, P = 0.03). Secondary endpoints that included blood viremia, acute rejection, and chronic lung allograft dysfunction did not differ between the 2 arms. Of the 80/118 patients who ceased antiviral prophylaxis at 5 months, the incidence of viremia (> 600 copies/mL) within the blood was significantly reduced in patients with a positive QFN-CMV assay compared with those without protective immunity (13% versus 67%, P = 0.0003), as was the incidence of severe viremia (> 10 000 copies/mL) (3% versus 50%, P < 0.001). Ceasing antiviral prophylaxis at 11 months in patients with a negative assay was associated with a 25% incidence of late CMV viremia. Conclusions. Cytomegalovirus immune monitoring allows an individualized approach to CMV prophylaxis and reduces late CMV infection within the lung allograft.

Clinical experience with a novel assay measuring cytomegalovirus (CMV)-specific CD4+ and CD8+ T-cell immunity by flow cytometry and intracellular cytokine staining to predict clinically significant CMV events

“…Over the last decade, there has been growing interest in the development and bedside implementation of CMV-CMI assays. The Quantiferon®-CMV assay can predict late-onset CMV disease after primary prophylaxis [10][11][12][13][14][15][16] and spontaneous clearance of CMV DNAemia [12,13,29]; it has also been used in two interventional studies to guide primary [16] or secondary (after treatment for a CMV event) [8] prophylaxis. ELISPOT-based CMV-CMI assays (T-Track CMV® and T-SPOT®-CMV) can also help predict CMV events [17][18][19][20][21][22][23][24][25][26].…”

“…To this end, several CMV-specific assays evaluating cell-mediated immunity (CMI) have been developed: The Quantiferon®-CMV assay exposes whole blood to 21 CMV epitopes. Interferon gamma (IFN-γ) released from activated CD8+ T-cells is then quantified via ELISA, allowing for a measure of CMV-specific CD8+ (but not CD4+) T-cell response [8][9][10][11][12][13][14][15][16]. The T-Track CMV® and T-SPOT®-CMV assays first isolate peripheral blood mononuclear cells (PBMC), then expose them to a variety of CMV antigens or lysates; the resulting IFN-γ is quantified via ELISpot allowing for a measure of aggregate CMV-specific CD4+/CD8+ Tcell and NK-cell response, but not its individual components [17][18][19][20][21][22][23][24][25][26].…”

Assessment and prevention of cytomegalovirus infection in allogeneic hematopoietic stem cell transplant and in solid organ transplant: A multidisciplinary consensus conference by the Italian GITMO, SITO, and AMCLI societies

“…In the majority of SOT patients, IGRAs can be performed at any time before and not earlier than 30 days after the transplant. In SOT experiences, IGRAs were performed before transplant, after transplant before CMV infection, or after CMV infection (Table ) . Positive IGRAs, both before and after SOT, were variably predictive of a lower risk of CMV infection/disease, longer CMV‐free period, spontaneous viral clearance, lower rate of CMV infection recurrence, and lower level of CMV DNAemia.…”

Use of T Cell Mediated Immune Functional Assays for Adjustment of Immunosuppressive or Anti-infective Agents in Solid Organ Transplant Recipients: A Systematic Review

“…In another clinical trial of 118 CMV seropositive lung transplant recipients, QuantiFERON®-CMV was used to guide the duration of antiviral prophylaxis ( 41 ). All the SOT recipients received antiviral prophylaxis for 5 months post-transplantation.…”