Cytomegalovirus viral load parameters associated with earlier initiation of pre-emptive therapy after solid organ transplantation

Sheila Lumley; Cameron Green; Hannah Rafferty; Colette Smith; Mark Harber; James O'Beirne; Gareth R Jones; Douglas Thorburn; Aileen Marshall; Tina Shah; Mohamed Zuhair; Emily Rothwell; Sowsan Atabani; Tanzina Haque; Paul David Griffiths

doi:10.1371/journal.pone.0210420

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Cytomegalovirus viral load parameters associated with earlier initiation of pre-emptive therapy after solid organ transplantation

Journal article

Open access

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Cytomegalovirus viral load parameters associated with earlier initiation of pre-emptive therapy after solid organ transplantation

Sheila Lumley, Cameron Green, Hannah Rafferty, Colette Smith, Mark Harber, James O'Beirne, Gareth R Jones, Douglas Thorburn, Aileen Marshall, Tina Shah, …

PLoS One, Vol.14(1), pp.1-11

2019

DOI: https://doi.org/10.1371/journal.pone.0210420

PMCID: PMC6347177

PMID: 30682032

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Abstract

cytomegalovirus

viral load

human cytomegalovirus (HCMV)

solid organ transplant

organ transplantation

Background: Human cytomegalovirus (HCMV) can be managed by monitoring HCMV DNA in the blood and giving valganciclovir when viral load exceeds a defined value. We hypothesised that such pre-emptive therapy should occur earlier than the standard 3000 genomes/ml (2520 IU/ml) when a seropositive donor transmitted virus to a seronegative recipient (D+R-) following solid organ transplantation (SOT). Methods: Our local protocol was changed so that D+R- SOT patients commenced valganciclovir once the viral load exceeded 200 genomes/ml; 168 IU/ml (new protocol). The decision point remained at 3000 genomes/ml (old protocol) for the other two patient subgroups (D+R+, D-R+). Virological outcomes were assessed three years later, when 74 D+R- patients treated under the old protocol could be compared with 67 treated afterwards. The primary outcomes were changes in peak viral load, duration of viraemia and duration of treatment in the D+R- group. The secondary outcome was the proportion of D+R- patients who developed subsequent viraemia episodes. Findings: In the D+R- patients, the median values of peak viral load (30,774 to 11,135 genomes/ml, p<0.0215) were significantly reduced on the new protocol compared to the old, but the duration of viraemia and duration of treatment were not. Early treatment increased subsequent episodes of viraemia from 33/58 (57%) to 36/49 (73%) of patients (p< 0.0743) with a significant increase (p = 0.0072) in those episodes that required treatment (16/58; 27% versus 26/49; 53%). Median peak viral load increased significantly (2,103 to 3,934 genomes/ml, p<0.0249) in the D+R+ but not in the D-R+ patient subgroups. There was no change in duration of viraemia or duration of treatment for any patient subgroup. Interpretation: Pre-emptive therapy initiated at the first sign of viraemia post-transplant significantly reduced the peak viral load but increased later episodes of viraemia, consistent with the hypothesis of reduced antigenic stimulation of the immune system.

Details

Title: Cytomegalovirus viral load parameters associated with earlier initiation of pre-emptive therapy after solid organ transplantation
Authors: Sheila Lumley (Author) - University College London
Cameron Green (Author) - University College London
Hannah Rafferty (Author) - University College London
Colette Smith (Author) - University College London
Mark Harber (Author) - Royal Free Hospital
James O'Beirne (Author) - Royal Free Hospital
Gareth R Jones (Author) - Royal Free Hospital
Douglas Thorburn (Author) - The Royal Free Hospital
Aileen Marshall (Author) - Royal Free Hospital
Tina Shah (Author) - Royal Free Hospital
Mohamed Zuhair (Author) - University College London
Emily Rothwell (Author) - University College London
Sowsan Atabani (Author) - University College London
Tanzina Haque (Author) - University College London
Paul David Griffiths (Author) - University College London
Publication details: PLoS One, Vol.14(1), pp.1-11
Publisher: Public Library of Science
Date published: 2019
DOI: 10.1371/journal.pone.0210420
ISSN: 1932-6203
PMID: 30682032; PMC6347177
Copyright note: © 2019 Lumley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Organisation Unit: University of the Sunshine Coast, Queensland; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99609708302621
Output Type: Journal article

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Web Of Science research areas: Immunology

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