CMV mRNA pp67/150 biomarker for CMV replication and clinical utility

• Research type

  Research Study

• Full title

  CMV mRNA pp67/150 as a biomarker for real time changes in CMV viral replication and clinical correlation with antiviral therapy and viraemia

• IRAS ID

  250258

• Contact name

  Samuel Moses

• Contact email

  samuel.moses@nhs.net

• Sponsor organisation

  East Kent Microbiology Services

• Duration of Study in the UK

  0 years, 6 months, 27 days

• Research summary

  the potential for reactivation. The infection is asymptomatic in immunocompetent individuals; however it can cause a life-threatening disease in immunocompromised individuals and is an important cause of morbidity and mortality in individuals also carrying human immunodeficiency virus (HIV) and recipients of solid organ and stem cell transplants. Up to 40% of renal transplant patients will develop clinical disease as a result of primary infection or viral reactivation, the treatment for which is most commonly ganciclovir, which acts as a nucleoside analogue causing DNA chain termination.
  There are new drugs that have been developed recently such as Letermovir that act at the later stage of HCMV viral replication targeting the terminase complex. Current CMV monitoring is by testing CMV DNA levels, which can remain high for 10-12 days after any effective action of Letermovir as the pre-existing translated DNA needs to be cycled out from the cellular compartment as Letermovir acts post DNA transcription. In contrast, the relationship of CMV DNA levels and ganciclvoir therapy is more linear as ganciclovir inhibits DNA formation. Therefore, a high CMV DNA whilst on these Letermovir does not give a clear idea whether the therapy is failing or whether it is pre-existing HCMV DNA that needs to be cycled out.

  Our proposal is to develop a CMV mRNA assay targeting late CMV protein translation target HCMV pp67 and other alternatives such as HCMV pp150.

  HCMV infection in renal transplant patients as a method for the assessment of letermovir treatment efficacy. The project objectives are:
  • Phase 1: Develop an assay to isolate and detect HCMV mRNA
  • Phase 2: Test the assay using human serum samples and compare this with a commercial DNA-based assay
  Depending on progress within current course:
  • Phase 3: Investigate the HCMV mRNA levels throughout the course of HCMV infection/reactivation in renal transplant patients)

• REC name

  Wales REC 6

• REC reference

  18/WA/0384

• Date of REC Opinion

  6 Nov 2018

• REC opinion

  Unfavourable Opinion