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

TY - JOUR

T1 - Clinical Application of Variation in Replication Kinetics During Episodes of Post-transplant Cytomegalovirus Infections

AU - Lodding, I P

AU - Sengeløv, Henrik

AU - da Cunha-Bang, C

AU - Iversen, Martin Peter

AU - Rasmussen, Allan

AU - Gustafsson, F

AU - Downing, J G

AU - Grarup, Jesper

AU - Kirkby, N

AU - Frederiksen, C M

AU - Mocroft, A

AU - Sørensen, S S

AU - Lundgren, Jens

AU - MATCH Programme Study Group

PY - 2015/7/1

Y1 - 2015/7/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.ebiom.2015.05.003

DO - 10.1016/j.ebiom.2015.05.003

M3 - Journal article

C2 - 26288842

SN - 2352-3964

VL - 2

SP - 699

EP - 705

JO - EBioMedicine

JF - EBioMedicine

IS - 7

ER -