Early administration of tecovirimat shortens the time to mpox clearance in a model of human infection
Nguyen, Bach (Institut national de la santé et de la recherche médicale (France))
Marc, Aurélien (Institut national de la santé et de la recherche médicale (France))
Suñer, Clara (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Marks, Michael (London School of Hygiene and Tropical Medicine. Clinical Research Department)
Ubals, Maria (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Hernandez-Rodriguez, Agueda (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Melendez, María Ángeles (Hospital 12 de Octubre (Madrid))
Hruby, Dennis E. (SIGA Technologies, Inc. (Corvallis))
Russo, Andrew T. (SIGA Technologies, Inc. (Corvallis))
Mentré, France (Institut national de la santé et de la recherche médicale (France))
Mitjà, Oriol (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Grosenbach, Douglas W. (SIGA Technologies, Inc. (Corvallis))
Guedj, Jérémie (Institut national de la santé et de la recherche médicale (France))

Fecha:	2023
Resumen:	Despite use of tecovirimat since the beginning of the 2022 outbreak, few data have been published on its antiviral effect in humans. We here predict tecovirimat efficacy using a unique set of data in nonhuman primates (NHPs) and humans. We analyzed tecovirimat antiviral activity on viral kinetics in NHP to characterize its concentration-effect relationship in vivo. Next, we used a pharmacological model developed in healthy volunteers to project its antiviral efficacy in humans. Finally, a viral dynamic model was applied to characterize mpox kinetics in skin lesions from 54 untreated patients, and we used this modeling framework to predict the impact of tecovirimat on viral clearance in skin lesions. At human-recommended doses, tecovirimat could inhibit viral replication from infected cells by more than 90% after 3 to 5 days of drug administration and achieved over 97% efficacy at drug steady state. With an estimated mpox within-host basic reproduction number, R0, equal to 5. 6, tecovirimat could therefore shorten the time to viral clearance if given before viral peak. We predicted that initiating treatment at symptom onset, which on average occurred 2 days before viral peak, could reduce the time to viral clearance by about 6 days. Immediate postexposure prophylaxis could not only reduce time to clearance but also lower peak viral load by more than 1. 0 log10 copies/mL and shorten the duration of positive viral culture by about 7 to 10 days. These findings support the early administration of tecovirimat against mpox infection, ideally starting from the infection day as a postexposure prophylaxis.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Dose prediction methods ; Lesions ; Viral load ; Blood plasma ; Antiviral therapy ; Viral clearance ; Virions ; Blood
Publicado en:	PLoS biology, Vol. 21, issue 12 (December 2023) , art. e3002249, ISSN 1545-7885

DOI: 10.1371/journal.pbio.3002249
PMID: 38127878

16 p, 1.6 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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