Abstract
BackgroundHuman 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).MethodsOur 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.FindingsIn 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.InterpretationPre-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.
Highlights
Cytomegalovirus (HCMV) is an important opportunistic pathogen in solid organ transplant (SOT) patients
Would it be possible in clinical practice to intervene early so that treatment was begun before viraemia reached 3000 genomes/ml, given[13] the rapid rate of Human cytomegalovirus (HCMV) replication? Would such earlier treatment translate into a lower peak viral load and shorter duration of viraemia? If so, would earlier initiation of pre-emptive therapy still provide sufficient antigen presentation to the immune system so that the number of future episodes of viraemia was not increased? To address these questions, we describe the results of 67 D+R- patients managed consecutively after the change in protocol and compare them with the published results in 74 D+R- patients managed under the old protocol
We describe the viral load parameters of a total of 960 kidney and liver transplant recipients, before (n = 566) and after (n = 394) a change in treatment protocol for the D+R- patients where treatment for the D+R+ and D-R+ patients remained the same throughout
Summary
Cytomegalovirus (HCMV) is an important opportunistic pathogen in solid organ transplant (SOT) patients. An analysis by the Cochrane database found 7 randomised controlled trials (RCT) that compared the two strategies, with no significant difference in any of four major clinical outcomes.[4] The results of RCTs of prophylactic therapy show that prophylaxis for 200 days post-transplant is superior to 100 days.[5] late onset disease, occurring once treatment is stopped, is seen in some patients managed using prophylaxis and may require the use of foscarnet to treat HCMV strains resistant to ganciclovir.[6] Resistant strains may be seen after pre-emptive therapy. 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)
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