Queen's School of Business Presentation
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Dialogues in Cytomegalovirus 3 CMV Management in the Post-DNA Polymerase Inhibitor Era Matthew P. Cheng, MD, FRCPC Dr. Matthew P. Cheng is an Assistant Professor in the Department of Medicine at McGill University, in Montreal. He leads the medical mycology laboratory and practices transplant infectious diseases at the McGill University Health Centre. Dr. Cheng obtained his medical degree from McGill University in 2011 and completed his residency in internal medicine at the University of British Columbia in 2014. He returned to McGill University to pursue a combined fellowship in infectious diseases and medical microbiology, which he finished in 2017. He completed a postdoctoral fellowship at the Harvard Medical School-affiliated Brigham and Women's Hospital and Dana-Farber Cancer Institute in 2019 before establishing his clinical research program at the McGill University Health Centre. Dr. Cheng's research interests include treating patients with potentially lethal infectious diseases, including opportunistic infections in immunocompromised hosts. His research program focuses on improving outcomes in these conditions by developing novel treatment strategies and diagnostic assays. His research is supported by the Fonds de Recherche Québec – Santé, the Canadian Institutes for Health Research, the US National Institutes of Health, and the Australian National Health and Medical Research Council. Dr. Cheng has been the recipient of numerous awards, including the New Investigator Award from the Association of Medical Microbiologists and Infectious Diseases Specialists of Canada and the prestigious Terry Fox Humanitarian Award. Affiliations: Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada Division of Medical Microbiology, Department of Laboratory Medicine, McGill University Health Centre, Montreal, Quebec, Canada McGill Interdisciplinary Initiative in Infection and Immunity, McGill University, Montreal, Quebec, Canada Background Cytomegalovirus (CMV) is a double-stranded DNA virus that is part of the Herpesviridae. Seroprevalence data suggest that 50% to 90% of the human population is infected with CMV depending on geographical location and socioeconomic factors. 1 The virus establishes latent infection in the human host and, under normal circumstances, is suppressed by the immune system. 2 However, the virus can reactivate during periods of immune suppression, including following solid organ transplantation (SOT) or allogeneic hematopoietic cell transplantation (allo-HCT). 3 If le› untreated, CMV replication can result in end- organ damage throughout the body and undesirable immunological outcomes including gra› versus host disease or organ rejection, 4,5 as well as increased morbidity and mortality post-transplantation. 6,7 Despite the availability of effective antivirals, CMV remains one of the most common viral diseases in the context of solid organ and stem cell transplantation. 8,9 Novel Antiviral Agents The search for effective antiviral agents against CMV resulted in the early discovery of three agents with similar mechanisms of action: ganciclovir and its oral prodrug valganciclovir, foscarnet and cidofovir. Ganciclovir functions by inhibiting CMV DNA polymerase (UL54) a›er it is phosphorylated intracellularly by a viral kinase (UL97) and cellular enzymes. 10 While both intravenous ganciclovir and oral valganciclovir are generally well tolerated, these agents are associated with increased rates of myelosuppression. These effects can occur in up to 40% of patients, generally following several weeks or months of usage. 10 Foscarnet and cidofovir directly inhibit CMV DNA polymerase and do not need to be activated by a viral kinase to exert their antiviral effects. 11,12 While foscarnet is more commonly used than cidofovir, both agents are administered intravenously and are associated with increased rates of renal toxicities, including acute kidney injury, electrolyte