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


CONCLUSIONS
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.
Centre for Virology University College London Medical School, London, United Kingdom.
Paul D
PD
Griffiths
Centre for Virology University College London Medical School, London, United Kingdom.
Emily
E
Rothwell
Centre for Virology University College London Medical School, London, United Kingdom.
Mohammed
M
Raza
Centre for Virology University College London Medical School, London, United Kingdom.
Stephanie
S
Wilmore
Centre for Virology University College London Medical School, London, United Kingdom.
Tomas
T
Doyle
Renal Transplant Unit Royal Free Hospital, London, United Kingdom.
Mark
M
Harber
The Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital, London, United Kingdom.
James
J
O'Beirne
Department of Haematology, University College London, London, United Kingdom.
Stephen
S
Mackinnon
Renal Transplant Unit Royal Free Hospital, London, United Kingdom.
Gareth
G
Jones
The Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital, London, United Kingdom.
Douglas
D
Thorburn
Centre for Virology University College London Medical School, London, United Kingdom.
Frank
F
Mattes
Centre for Virology University College London Medical School, London, United Kingdom.
Gaia
G
Nebbia
Centre for Virology University College London Medical School, London, United Kingdom.
Sowsan
S
Atabani
Research Department of Infection and Population Health, University College London, London, United Kingdom.
Colette
C
Smith
Centre for Virology University College London Medical School, London, United Kingdom.
Anna
A
Stanton
Centre for Virology University College London Medical School, London, United Kingdom.
Vincent C
VC
Emery
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