Clinical Application of Variation in Replication Kinetics During Episodes of Post-transplant Cytomegalovirus Infections

Abstract

Background: Cytomegalovirus (CMV) infection in transplant recipients is reported to replicate with a doubling time of 1.2–2 days, and weekly screening is recommended for early diagnosis. We re-evaluated these features in our cohort of transplant recipients. Methods: The CMV doubling time of the first CMV infection in the first year post-transplant could be calculated for 193 recipients of haematopoietic stem cell or solid organ transplantation. Factors determining the proportion of recipients with a high diagnostic CMV viral load (≥18,200 IU/mL) were explored using mathematical simulation. Findings: The overall median doubling time was 4.3 days (IQR 2.5–7.8) and was not influenced by prior CMV immunity, or type of transplantation (p > 0.4). Assuming a fixed doubling time of 1.3 days and screening intervals of 7 or 10 days, 11.1% and 33.3% were projected to have a high CMV viral load at diagnosis, compared to 1.4% and 4.3% if the doubling time varies as observed in our cohort. Consistently, 1.9% of recipients screened weekly had a high diagnostic virus load. Interpretation: Screening intervals can be extended to 10 days in cohorts with comparable CMV doubling time, whereas shorter than 7 days is required in cohorts with shorter doubling times to maintain pre-emptive screening quality.

Keywords

• Cytomegalovirus
• PCR
• Solid organ transplantation
• Haematopoietic stem cell transplantation
• Pre-emptive treatment
• Doubling time