CMV Infection Clinical Trial
Official title:
Does CMV Reactivation Cause Functional Impairment of CMV Specific CD4+ T-cells? The Potential for Valaciclovir to Prevent CMV-mediated Adverse Modulation of the Immune System in Patients With ANCA-associated Vasculitis
The purpose of this study is to determine whether Cytomegalovirus (CMV) reactivation in
ANCA-associated vasculitis (AAV) patients can be effectively and safely reduced using an
antiviral agent (valaciclovir) and whether this in turn improves the function of the immune
system thereby also improving the body's ability to fight other infections.
The primary hypothesis is that repeated episodes of CMV reactivation in AAV patients drive
the expansion and functional impairment of CMV-specific T-cells, with increased
susceptibility to infection. Inhibition of CMV replication with valaciclovir will block
further stimulation of CMV specific T-cells and increase the functional capacity of the
immune system.
Infection is the commonest cause of death in patients with ANCA-associated vasculitis (AAV).
The investigators have shown that the expansion of CD4+CD28- T-cells present in patients
with AAV is driven by CMV and this expansion is associated with increased infection risk. It
is suggested that these cells are driven by CMV reactivation and express markers of T-cell
exhaustion with reduced cytokine production and inhibitory receptor expression. However the
phenotype of CMV-specific T cells in those with extreme expansions of CD4+CD28- T-cells has
not been explored.
The investigators aim to investigate the phenotype of CMV-specific T-cells comparing those
patients with extreme expansions of CD4+CD28- T-cells to those with smaller expansions and
relate this to CMV reactivation. The investigators will monitor CMV reactivation in urine
and blood monthly by qPCR. This will be correlated with the expansion of CD4+CD28- T-cells
and the phenotype of these cells, specifically looking at cytokine production and inhibitory
receptor expression. The investigators will identify CMV-specific T-cells by MHC class II
tetramers or by stimulating with CMV lysate. The investigators will proceed to undertake a
randomised controlled trial with valaciclovir or no treatment to investigate whether the
reduction of CMV reactivation improves the phenotype of CD4+CD28- T-cells in these patients.
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Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science
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