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Griffiths PD, Rothwell E, Raza M, et al. Randomized Controlled Trials to Define Viral Load Thresholds for Cytomegalovirus Pre-Emptive Therapy. PLoS One. 2016;11(9):e0163722doi: 10.1371/journal.pone.0163722.
Griffiths, P. D., Rothwell, E., Raza, M., Wilmore, S., Doyle, T., Harber, M., O'Beirne, J., Mackinnon, S., Jones, G., Thorburn, D., Mattes, F., Nebbia, G., Atabani, S., Smith, C., Stanton, A., & Emery, V. C. (2016). Randomized Controlled Trials to Define Viral Load Thresholds for Cytomegalovirus Pre-Emptive Therapy. PloS one, 11(9), e0163722. https://doi.org/10.1371/journal.pone.0163722
Griffiths, Paul D, et al. "Randomized Controlled Trials to Define Viral Load Thresholds for Cytomegalovirus Pre-Emptive Therapy." PloS one vol. 11,9 (2016): e0163722. doi: https://doi.org/10.1371/journal.pone.0163722
Griffiths PD, Rothwell E, Raza M, Wilmore S, Doyle T, Harber M, O'Beirne J, Mackinnon S, Jones G, Thorburn D, Mattes F, Nebbia G, Atabani S, Smith C, Stanton A, Emery VC. Randomized Controlled Trials to Define Viral Load Thresholds for Cytomegalovirus Pre-Emptive Therapy. PLoS One. 2016 Sep 29;11(9):e0163722. doi: 10.1371/journal.pone.0163722. eCollection 2016. PMID: 27684379; PMCID: PMC5042415.
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PLoS One. 2016 Sep 29;11(9):e0163722. doi: 10.1371/journal.pone.0163722. eCollection 2016.

Randomized Controlled Trials to Define Viral Load Thresholds for Cytomegalovirus Pre-Emptive Therapy.

PloS one

Paul D Griffiths, Emily Rothwell, Mohammed Raza, Stephanie Wilmore, Tomas Doyle, Mark Harber, James O'Beirne, Stephen Mackinnon, Gareth Jones, Douglas Thorburn, Frank Mattes, Gaia Nebbia, Sowsan Atabani, Colette Smith, Anna Stanton, Vincent C Emery

Affiliations

  1. Centre for Virology University College London Medical School, London, United Kingdom.
  2. Renal Transplant Unit Royal Free Hospital, London, United Kingdom.
  3. The Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital, London, United Kingdom.
  4. Department of Haematology, University College London, London, United Kingdom.
  5. Research Department of Infection and Population Health, University College London, London, United Kingdom.

PMID: 27684379 PMCID: PMC5042415 DOI: 10.1371/journal.pone.0163722

Abstract

BACKGROUND: To help decide when to start and when to stop pre-emptive therapy for cytomegalovirus infection, we conducted two open-label randomized controlled trials in renal, liver and bone marrow transplant recipients in a single centre where pre-emptive therapy is indicated if viraemia exceeds 3000 genomes/ml (2520 IU/ml) of whole blood.

METHODS: Patients with two consecutive viraemia episodes each below 3000 genomes/ml were randomized to continue monitoring or to immediate treatment (Part A). A separate group of patients with viral load greater than 3000 genomes/ml was randomized to stop pre-emptive therapy when two consecutive levels less than 200 genomes/ml (168 IU/ml) or less than 3000 genomes/ml were obtained (Part B). For both parts, the primary endpoint was the occurrence of a separate episode of viraemia requiring treatment because it was greater than 3000 genomes/ml.

RESULTS: In Part A, the primary endpoint was not significantly different between the two arms; 18/32 (56%) in the monitor arm had viraemia greater than 3000 genomes/ml compared to 10/27 (37%) in the immediate treatment arm (p = 0.193). However, the time to developing an episode of viraemia greater than 3000 genomes/ml was significantly delayed among those randomized to immediate treatment (p = 0.022). In Part B, the primary endpoint was not significantly different between the two arms; 19/55 (35%) in the less than 200 genomes/ml arm subsequently had viraemia greater than 3000 genomes/ml compared to 23/51 (45%) among those randomized to stop treatment in the less than 3000 genomes/ml arm (p = 0.322). However, the duration of antiviral treatment was significantly shorter (p = 0.0012) in those randomized to stop treatment when viraemia was less than 3000 genomes/ml.

DISCUSSION: The results illustrate that patients have continuing risks for CMV infection with limited time available for intervention. We see no need to alter current rules for stopping or starting pre-emptive therapy.

Conflict of interest statement

The authors have declared that no competing interests exist.

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