Tecovirimat Resistance in Mpox Patients, United States, 2022-2023

• Published in: Emerging infectious diseases Vol. 29; no. 12; pp. 2426 - 2432
• Main Authors: Smith, Todd G, Gigante, Crystal M, Wynn, Nhien T, Matheny, Audrey, Davidson, Whitni, Yang, Yong, Condori, Rene Edgar, O'Connell, Kyle, Kovar, Lynsey, Williams, Tracie L, Yu, Yon C, Petersen, Brett W, Baird, Nicolle, Lowe, David, Li, Yu, Satheshkumar, Panayampalli S, Hutson, Christina L
• Format: Journal Article
• Language: English
• Published: United States U.S. National Center for Infectious Diseases 01.12.2023; Centers for Disease Control and Prevention
• Subjects: Amino acids; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Antiviral drugs; antivirals; Benzamides - therapeutic use; Biological Assay; Disease control; Drug resistance; Drug therapy; Genomes; Genotype & phenotype; Health aspects; Health surveillance; HIV; Human immunodeficiency virus; Human monkeypox; Humans; Infection; Infections; Monkeypox; Monkeypox virus; mpox; Mpox (monkeypox); Mutation; Patient outcomes; Patients; Pharmaceutical industry; Prevention; Proteins; Smallpox; ST-246; tecovirimat; Tecovirimat Resistance in Mpox Patients, United States, 2022–2023; TPOXX; United States - epidemiology; viruses; United States; United States > US; California; antivirals; tecovirimat; viruses; United States; antimicrobial resistance; TPOXX; orthopoxvirus; monkeypox virus; ST-246; mpox
• ISSN: 1080-6040; 1080-6059
• DOI: 10.3201/eid2912.231146

During the 2022 multinational outbreak of monkeypox virus (MPXV) infection, the antiviral drug tecovirimat (TPOXX; SIGA Technologies, Inc., https://www.siga.com) was deployed in the United States on a large scale for the first time. The MPXV F13L gene homologue encodes the target of tecovirimat, and single amino acid changes in F13 are known to cause resistance to tecovirimat. Genomic sequencing identified 11 mutations previously reported to cause resistance, along with 13 novel mutations. Resistant phenotype was determined using a viral cytopathic effect assay. We tested 124 isolates from 68 patients; 96 isolates from 46 patients were found to have a resistant phenotype. Most resistant isolates were associated with severely immunocompromised mpox patients on multiple courses of tecovirimat treatment, whereas most isolates identified by routine surveillance of patients not treated with tecovirimat remained sensitive. The frequency of resistant viruses remains relatively low (<1%) compared with the total number of patients treated with tecovirimat.