| Title: |
Early administration of tecovirimat shortens the time to mpox clearance in a model of human infection |
| Authors: |
Nguyen, Bach; Marc, Aurélien; Suñer, Clara; Marks, Michael; Ubals, Maria; Hernandez-Rodriguez, Agueda; Melendez, María Ángeles; Hruby, Dennis E.; Russo, Andrew T.; Mentré, France; Mitjà, Oriol; Grosenbach, Douglas W.; Guedj, Jérémie |
| Publication Year: |
2023 |
| Collection: |
Universitat Autònoma de Barcelona: Dipòsit Digital de Documents de la UAB |
| Subject Terms: |
Dose prediction methods; Lesions; Viral load; Blood plasma; Antiviral therapy; Viral clearance; Virions; Blood |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
PLoS biology; Vol. 21, issue 12 (December 2023), art. e3002249; https://ddd.uab.cat/record/311186; urn:10.1371/journal.pbio.3002249; urn:oai:ddd.uab.cat:311186; urn:pmcid:PMC10734935; urn:oai:pubmedcentral.nih.gov:10734935; urn:pmid:38127878 |
| Availability: |
https://ddd.uab.cat/record/311186 |
| Rights: |
open access ; 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. ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.AE4C0183 |
| Database: |
BASE |