Impact of an Ultrasensitive Cytomegalovirus (CMV) Quantitative Nucleic Acid Test (qNAT) on CMV Detection and Therapy in Renal Transplant Recipients Open Access

Abstract

Background: Cytomegalovirus (CMV) infection has broad implications for morbidity and mortality in renal transplant recipients (RTR). Routine surveillance for CMV replication with PCR-based quantitative nucleic acid testing (qNAT) assays is standard practice in most transplant centers, but the impact of assay sensitivity on antiviral decision-making and virologic outcomes has not been studied. We investigated the effects of an ultrasensitive CMV qNAT assay on clinical outcomes, including time to detection and duration of CMV DNAemia.

 

Methods: We conducted a single-center cohort study comparing RTRs monitored with a qNAT with a higher lower limit of quantification (LLOQ> 300 IU/mL) with those monitored with a more sensitive qNAT (LLOQ> 35 IU/mL). Patients were stratified by donor (D)/recipient (R) CMV serostatus (D+/R-, high-risk; any R+, moderate-risk). CMV viral load monitoring was performed monthly post-transplantation according to Emory Transplant Center protocols, with the primary outcomes being time to CMV DNAemia and its duration.

 

Results: 1382 patients were analyzed from 2014-2016 and 2019-2021. Moderate-risk RTRs monitored with the more sensitive assay experienced a greater hazard for the development of a first episode of CMV DNAemia (aHR- 1.95 95% CI- 1.55 to 2.46) and an average of 24 (95% CI- 16.40 to 31.98) additional days of DNAemia after reaching the 1,000 IU/mL threshold compared to those tested with the less sensitive assay. There was no difference in CMV end-organ disease or one-year all-cause mortality between moderate-risk RTRs.

 

Conclusions: The more sensitive assay was associated with earlier detection and extended durations of CMV DNAemia in moderate-risk RTRs, without altering clinical outcomes. These findings inform optimal use of these assays and antiviral stewardship in RTRs.

Table of Contents

Table of Contents

Introduction - 1

Methods - 8

Results - 14

Discussion - 18

References - 22

Tables- 26

Table 1- CMV Risk Stratification by Serostatus:- 26

Table 2: Baseline patient characteristics of renal transplant recipients- 27

Table 3- Hazard Ratios for time to CMV DNAemia: - 29

Table 4- Linear regression estimates for duration of CMV DNAemia:- 30

Table 5- Secondary outcomes:- 31

Table 6 Odds ratios for end-organ disease- 32

Table 7- Cause of death arranged by CMV risk status.- 33

Figures- 34

Figure 1: Flow diagram- 34

Figure 2: Directed Acyclic Graph for the primary exposure, PCR platform used, and outcome- time to CMV DNAemia.- 35

Figure 3: Directed Acyclic Graph for the primary exposure, PCR platform used, and outcome- duration of CMV DNAemia.- 36

Figure 4- Kaplan Meier curve analysis- 37

About this Master's Thesis

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School	Laney Graduate School
Department	Clinical Research
Degree	M.S.
Submission	Master's Thesis
Language	English
Research Field	Biology, Virology Health Sciences, Medicine and Surgery
Keyword	PCR CMV Renal Transplant
Committee Chair / Thesis Advisor	Amita Manatunga, Emory University Jordan Kempker, Emory University
Committee Members	Michael Woodworth, Emory University Ahmed Babiker, Emory University

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