Randomized Controlled Trials to Define Viral Load Thresholds for Cytomegalovirus Pre-Emptive Therapy.
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/m...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5042415?pdf=render |
| _version_ | 1811234596871733248 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Paul D Griffiths |
| collection | DOAJ |
| description | 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.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.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.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. |
| first_indexed | 2024-04-12T11:38:52Z |
| format | Article |
| id | doaj.art-a73f4fbee9444bdabe09a02f4054da3d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T11:38:52Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a73f4fbee9444bdabe09a02f4054da3d2022-12-22T03:34:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01119e016372210.1371/journal.pone.0163722Randomized Controlled Trials to Define Viral Load Thresholds for Cytomegalovirus Pre-Emptive Therapy.Paul D GriffithsEmily RothwellMohammed RazaStephanie WilmoreTomas DoyleMark HarberJames O'BeirneStephen MackinnonGareth JonesDouglas ThorburnFrank MattesGaia NebbiaSowsan AtabaniColette SmithAnna StantonVincent C EmeryTo 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.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.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.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.http://europepmc.org/articles/PMC5042415?pdf=render |
| spellingShingle | 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 Randomized Controlled Trials to Define Viral Load Thresholds for Cytomegalovirus Pre-Emptive Therapy. PLoS ONE |
| title | Randomized Controlled Trials to Define Viral Load Thresholds for Cytomegalovirus Pre-Emptive Therapy. |
| title_full | Randomized Controlled Trials to Define Viral Load Thresholds for Cytomegalovirus Pre-Emptive Therapy. |
| title_fullStr | Randomized Controlled Trials to Define Viral Load Thresholds for Cytomegalovirus Pre-Emptive Therapy. |
| title_full_unstemmed | Randomized Controlled Trials to Define Viral Load Thresholds for Cytomegalovirus Pre-Emptive Therapy. |
| title_short | Randomized Controlled Trials to Define Viral Load Thresholds for Cytomegalovirus Pre-Emptive Therapy. |
| title_sort | randomized controlled trials to define viral load thresholds for cytomegalovirus pre emptive therapy |
| url | http://europepmc.org/articles/PMC5042415?pdf=render |
| work_keys_str_mv | AT pauldgriffiths randomizedcontrolledtrialstodefineviralloadthresholdsforcytomegaloviruspreemptivetherapy AT emilyrothwell randomizedcontrolledtrialstodefineviralloadthresholdsforcytomegaloviruspreemptivetherapy AT mohammedraza randomizedcontrolledtrialstodefineviralloadthresholdsforcytomegaloviruspreemptivetherapy AT stephaniewilmore randomizedcontrolledtrialstodefineviralloadthresholdsforcytomegaloviruspreemptivetherapy AT tomasdoyle randomizedcontrolledtrialstodefineviralloadthresholdsforcytomegaloviruspreemptivetherapy AT markharber randomizedcontrolledtrialstodefineviralloadthresholdsforcytomegaloviruspreemptivetherapy AT jamesobeirne randomizedcontrolledtrialstodefineviralloadthresholdsforcytomegaloviruspreemptivetherapy AT stephenmackinnon randomizedcontrolledtrialstodefineviralloadthresholdsforcytomegaloviruspreemptivetherapy AT garethjones randomizedcontrolledtrialstodefineviralloadthresholdsforcytomegaloviruspreemptivetherapy AT douglasthorburn randomizedcontrolledtrialstodefineviralloadthresholdsforcytomegaloviruspreemptivetherapy AT frankmattes randomizedcontrolledtrialstodefineviralloadthresholdsforcytomegaloviruspreemptivetherapy AT gaianebbia randomizedcontrolledtrialstodefineviralloadthresholdsforcytomegaloviruspreemptivetherapy AT sowsanatabani randomizedcontrolledtrialstodefineviralloadthresholdsforcytomegaloviruspreemptivetherapy AT colettesmith randomizedcontrolledtrialstodefineviralloadthresholdsforcytomegaloviruspreemptivetherapy AT annastanton randomizedcontrolledtrialstodefineviralloadthresholdsforcytomegaloviruspreemptivetherapy AT vincentcemery randomizedcontrolledtrialstodefineviralloadthresholdsforcytomegaloviruspreemptivetherapy |