Meesing, Atibordee

Abstract Background Quantitative nucleic acid amplification (QNAT) tests are cornerstone for the management of CMV disease after organ transplantation. We assessed the potential impact of viral load results obtained by two commercial WHO international standard-calibrated NAT in solid-organ (SOT) and hematopoietic stem cell transplant (HSCT) recipients. Methods Sixty-four patients (36 SOT and 28 HSCT) had plasma CMV viral load assessed using the COBAS AmpliPrep/COBAS TaqMan CMV Test (CAP/CTM; lower limit of quantification [LLoQ] at 137 IU/mL) and cobas 6800 System (cobas CMV; LLoQ at 35 IU/mL). Viral load values were correlated with clinical course and outcomes. Results Forty-three of 64 patients (67.2%) had CMV infection or disease (asymptomatic, 67.4%; gastrointestinal disease, 16.3%; pneumonitis 4.7%) at median of 4.4 months (IQR 1.4 to 7.7) from transplantation. At CMV infection diagnosis, viral load results (mean ± SD) were almost two-fold higher when measured by cobas CMV (19,456 ± 51,618 IU/mL) compared with CAP/CTM (10,504 ± 27,744 IU/mL; P = 0.04). Time to onset of CMV viremia was significantly shorter (11.5 days; P < 0.001) while viral clearance was significantly longer (12.75 days; P < 0.001) by cobas CMV when compared with CAP/CTM. Persistent viremia was observed with cobas CMV in 44% of patients at the time of first negative results by CAP/CTM. Patients with negative results by cobas CMV at the end of antiviral treatment had a significantly lower need for re-treatment (OR 0.26, 95% CI 0.04 to 0.99, P = 0.05). Conclusion Our study highlights significant differences between CMV QNAT assays despite calibration to the WHO-international standard. The significant differences in the degree (almost two-fold), time to onset (12 days difference) and clearance (13 days difference) of CMV viremia between two automated commercial QNAT assays have direct implications in the care of transplant recipients. Persistence of low-level viremia was observed in samples that reached negative threshold by CAP/CTM, when tested using the more sensitive cobas CMV. Clearance of CMV viremia, when assessed by the more sensitive cobas CMV, was significantly associated with a lower need for re-treatment. Disclosures All authors: No reported disclosures.

AbstractCytomegalovirus (CMV) viral loads overall were 0.29 log IU/mL higher with cobas CMV for use on the cobas 6800/8800 System (cobas CMV) compared with Cobas AmpliPrep/Cobas TaqMan CMV Test (CAP/CTM CMV). Cytomegalovirus DNAemia was detected 11.5 days earlier by cobas CMV, whereas clearance was delayed by 12.8 days. Cytomegalovirus remained detectable by cobas CMV in 44.2% of patients at the time of viral clearance as determined by CAP/CTM CMV. Undetectable viral load by cobas CMV at end of treatment was associated with reduced risk for retreatment (odds ratio, 0.26; 95% confidence interval, 0.04–0.99; P = .05).The use of different quantitative cytomegalovirus nucleic acid tests may affect direct patient care as a result of significant differences in reporting the degree of CMV DNAemia and the time to first detection and clearance of CMV DNAemia.

AbstractThis study of 64 solid organ and hematopoietic stem cell transplant recipients found that peripheral blood absolute lymphocyte count of &lt;610 and &lt;830/µL, respectively, correlated with cytomegalovirus infection. In an era when sophisticated measures of CMV-specific T cells are emerging, we emphasize the utility of the inexpensive and readily-available absolute lymphocyte count.

Background. Control of cytomegalovirus (CMV) infection after solid organ transplantation (SOT) requires a functional immune system. We assessed the association between quantitation and function of CMV-specific CD8+ T cells and CMV infection in SOT recipients. Methods. During a 10-year period, selected kidney, heart, lung, pancreas, liver, and composite tissue recipients were tested for CMV-specific CD8+ T cells immune competence (CMV-CD8+), as measured by enumeration, interferon-gamma production, and CD107a/b degranulation. Quantitative and functional data were used to assemble T-cell immune competence (TIC) score. CMV infection was diagnosed by polymerase chain reaction in blood and other samples or histopathology. Results. Of 130 patients tested, 59 had CMV infection or disease. The median onset to CMV infection was 10.5 months (interquartile range [IQR], 5.5–18.7). Gastrointestinal disease (28.8%), pneumonia (20.3%), and CMV syndrome (17%) were most common presentation. An impaired nonspecific or CMV-CD8+ TIC score was associated with tissue-invasive disease (hazard risk, 2.84, 95% confidence interval, 1.03–11.81; P = 0.04). Patients with impaired CMV-CD8+ TIC score had longer viremia duration (42.4 days vs 18.8 d; P < 0.001). Patients with impaired nonspecific or CMV-CD8+ TIC score had higher risk of relapse (68.8% vs 27.9%; hazard risk, 2.56; 95% confidence interval, 1.09–5.89; P = 0.03). Patients with CMV infection or disease had lower median absolute lymphocyte count (380 [IQR, 240–540] vs 940 [IQR, 551–1210] cells/mm 3 ; P < 0.0001) and CD4+ T cell count (29 cells/mm 3 [IQR, 1.3–116.0] vs 325.5 cells/mm 3 [IQR, 151.5–589.8]; P < 0.0001). Conclusions. Nonspecific and CMV-specific CD8+ T-cell function correlated with the course of CMV after SOT, and measuring these has the potential to assist in its clinical management.