Effect of remdesivir on viral dynamics in COVID-19 hospitalized patients: a modelling analysis of the randomized, controlled, open-label DisCoVeRy trial.
J Antimicrob Chemother
; 77(5): 1404-1412, 2022 04 27.
Article
en En
| MEDLINE
| ID: mdl-35233617
ABSTRACT
BACKGROUND:
The antiviral efficacy of remdesivir in COVID-19 hospitalized patients remains controversial.OBJECTIVES:
To estimate the effect of remdesivir in blocking viral replication.METHODS:
We analysed nasopharyngeal normalized viral loads from 665 hospitalized patients included in the DisCoVeRy trial (NCT04315948; EudraCT 2020-000936-23), randomized to either standard of care (SoC) or SoC + remdesivir. We used a mathematical model to reconstruct viral kinetic profiles and estimate the antiviral efficacy of remdesivir in blocking viral replication. Additional analyses were conducted stratified on time of treatment initiation (≤7 or >7â days since symptom onset) or viral load at randomization (< or ≥3.5 log10 copies/104 cells).RESULTS:
In our model, remdesivir reduced viral production by infected cells by 2-fold on average (95% CI 1.5-3.2-fold). Model-based simulations predict that remdesivir reduced time to viral clearance by 0.7â days compared with SoC, with large inter-individual variabilities (IQR 0.0-1.3â days). Remdesivir had a larger impact in patients with high viral load at randomization, reducing viral production by 5-fold on average (95% CI 2.8-25-fold) and the median time to viral clearance by 2.4â days (IQR 0.9-4.5â days).CONCLUSIONS:
Remdesivir halved viral production, leading to a median reduction of 0.7â days in the time to viral clearance compared with SoC. The efficacy was larger in patients with high viral load at randomization.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tratamiento Farmacológico de COVID-19
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Antimicrob Chemother
Año:
2022
Tipo del documento:
Article
País de afiliación:
Francia