CMV Modulation of the Immune System in ANCA-associated Vasculitis

Summary

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.

Timeline

Start

2013-07

Primary completion

2016-02

Completion

2017-09

Publications

• Background Morgan MD, Pachnio A, Begum J, Roberts D, Rasmussen N, Neil DA, Bajema I, Savage CO, Moss PA, Harper L. CD4+CD28- T cell expansion in granulomatosis with polyangiitis (Wegener's) is driven by latent cytomegalovirus infection and is associated with an increased risk of infection and mortality. Arthritis Rheum. 2011 Jul;63(7):2127-37. doi: 10.1002/art.30366.
• Chanouzas D, Sagmeister M, Faustini S, Nightingale P, Richter A, Ferro CJ, Morgan MD, Moss P, Harper L. Subclinical Reactivation of Cytomegalovirus Drives CD4+CD28null T-Cell Expansion and Impaired Immune Response to Pneumococcal Vaccination in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. J Infect Dis. 2019 Jan 7;219(2):234-244. doi: 10.1093/infdis/jiy493.
• Chanouzas D, Dyall L, Nightingale P, Ferro C, Moss P, Morgan MD, Harper L. Valaciclovir to prevent Cytomegalovirus mediated adverse modulation of the immune system in ANCA-associated vasculitis (CANVAS): study protocol for a randomised controlled trial. Trials. 2016 Jul 22;17(1):338. doi: 10.1186/s13063-016-1482-2.
• Chanouzas D, Dyall L, Dale J, Moss P, Morgan M, Harper L. CD4+CD28- T-cell expansions in ANCA-associated vasculitis and association with arterial stiffness: baseline data from a randomised controlled trial. Lancet. 2015 Feb 26;385 Suppl 1:S30. doi: 10.1016/S0140-6736(15)60345-2.

Drugs

Indications