Treatment of cytomegalovirus infection and disease pre‐ and post‐quantitative nucleic acid test standardization: does use of a more sensitive assay lead to longer treatment duration?

Abstract

Quantitative cytomegalovirus (CMV) nucleic acid testing (NAT) has been standardized using the World Health Organization (WHO) international calibration standard. A new FDA-approved WHO-calibrated assay (CA) was found to be more sensitive than a laboratory-developed test (LDT). We hypothesized that monitoring therapeutic response using a more sensitive assay may lead to longer antiviral therapy in solid organ and hematopoietic stem cell transplant patients with CMV infection. We reviewed transplant patients with CMV disease retrospectively, and divided them into two groups: those diagnosed and managed based on LDT and those managed using WHO-CA. Compared to patients monitored by LDT, the time to reach an undetectable viral load was significantly longer in the group monitored by the WHO-CA. However, a trend toward shorter duration of antiviral treatment was observed (median, 34 vs. 41 d; p = 0.058), with earlier discontinuation of induction antiviral therapy upon reaching undetectable viral load using WHO-CA (11 vs. 18 d; p = 002). We concluded that despite using a more sensitive CMV NAT, the total duration of antiviral treatment was not significantly prolonged in transplant patients with CMV infection and disease. Relapse rates did not differ between the two groups.

The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation

“…A recent study showed that using a more sensitive test does increase the time to reach an undetectable viral load; however, there was a trend towards shorter duration of therapy with the more sensitive assay. 55 Finally, treatment until viral load values are less than 137 IU/mL is predictive of a clinical response. 56 Though there is value to using highly sensitive assays, the practice of continuing therapy until successive viral load tests are undetectable may not be necessary when using such tests (ie, with highly sensitive assays, multiple very low results might be sufficient before stopping therapy).…”

Transition from antigenemia to quantitative nucleic acid amplification testing in cytomegalovirus-seropositive kidney transplant recipients receiving preemptive therapy for cytomegalovirus infection

“…There was an initial concern that highly sensitive assays to manage the CMV infection resulted in prolonged treatments and unnecessary exposure to antiviral therapy 14 . However, a shorter time of treatment using standardized quantitative nucleic acid testing has been demonstrated in a previous study 17 , 18 . Additionally, as a direct consequence of a more prolonged treatment time with RT-PCR observed in our study, we expected that the rate of the retreating requirement was reduced, considering that reaching a virological suppression seems to be predictive of clinical response 17 .…”

Prevention of Cytomegalovirus Infection in Solid Organ Transplant Recipients: Guidelines by the Korean Society of Infectious Diseases and the Korean Society for Transplantation

“…Failure to eradicate plasma DNAemia at the end of treatment is the major significant predictor of virologic recurrence [ 126 ]. Two consecutive negative weekly CMV QNAT results were previously suggested (in studies that used less sensitive CMV QNAT assays), but a single negative test may suffice if a highly sensitive QNAT is performed [ 127 128 ]. The highly sensitive test in the aforementioned studies is the WHO-calibrated assay, which corresponds to the test used in hospitals in Korea.…”