Advances in the Development of Therapeutics for Cytomegalovirus Infections

• Published in: The Journal of infectious diseases Vol. 221; no. Supplement_1; pp. S32 - S44
• Main Authors: Acosta, Edward, Bowlin, Terry, Brooks, Jennifer, Chiang, Lillian, Hussein, Islam, Kimberlin, David, Kauvar, Lawrence M, Leavitt, Randi, Prichard, Mark, Whitley, Richard
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 05-03-2020
• Subjects: Acetates - administration & dosage; Acetates - adverse effects; Acetates - therapeutic use; Antiviral agents; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Antiviral drugs; Biomarkers; Clinical Studies as Topic; Cytomegalovirus; Cytomegalovirus - drug effects; Cytomegalovirus Infections - drug therapy; Cytomegalovirus Infections - prevention & control; Cytomegalovirus Infections - transmission; Cytomegalovirus Infections - virology; Drug Development; Drug Resistance, Viral; Ganciclovir; HIV; Human immunodeficiency virus; Humans; Infections; Infectious Disease Transmission, Vertical; Monoclonal antibodies; Pediatrics; Population studies; Quinazolines - administration & dosage; Quinazolines - adverse effects; Quinazolines - therapeutic use; Research Design; Sirtuins; Sirtuins - administration & dosage; Sirtuins - adverse effects; Sirtuins - therapeutic use; Stem Cell Transplantation - adverse effects; Stem Cell Transplantation - methods; Supplement; Treatment Outcome; Viral Load; letermovir; congenital cytomegalovirus; sirtuins; valganciclovir; ganciclovir; cyclopropovir; antiviral therapy; maribavir; monoclonal antibodies
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiz493

Abstract
The development of therapeutics for cytomegalovirus (CMV) infections, while progressing, has not matched the pace of new treatments of human immunodeficiency virus (HIV) infections; nevertheless, recent developments in the treatment of CMV infections have resulted in improved human health and perhaps will encourage the development of new therapeutic approaches. First, the deployment of ganciclovir and valganciclovir for both the prevention and treatment of CMV infections and disease in transplant recipients has been further improved with the licensure of the efficacious and less toxic letermovir. Regardless, late-onset CMV disease, specifically pneumonia, remains problematic. Second, the treatment of congenital CMV infections with valganciclovir has beneficially improved both hearing and neurologic outcomes, both fundamental advances for these children. In these pediatric studies, viral load was decreased but not eliminated. Thus, an important lesson learned from studies in both populations is the need for new antiviral agents and the necessity for combination therapies as has been shown to be beneficial in the treatment of HIV infections, among others. The development of monoclonal antibodies, sirtuins, and cyclopropovir may provide new treatment options.