Titre :

Effect of Remdesivir on Viral Dynamics in COVID-19 Hospitalized Patients: A Modelling Analysis of the Randomized, Controlled, Open-Label DisCoVeRy Trial

Auteur(s) :

Bouscambert-Duchamp, Maude [Auteur]
Centre International de Recherche en Infectiologie [CIRI]
Hospices Civils de Lyon [HCL]
Virology and human respiratory Pathologies - Virology and human respiratory Pathologies [CIRI] [VirPath]
Lingas, Guillaume [Auteur]
Infection, Anti-microbiens, Modélisation, Evolution [IAME (UMR_S_1137 / U1137)]
Néant, Nadège [Auteur]
Infection, Anti-microbiens, Modélisation, Evolution [IAME (UMR_S_1137 / U1137)]
Gaymard, Alexandre [Auteur]
Institut des Agents Infectieux [Lyon] [IAI]
Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] [CNR - laboratoire associé]
Virology and human respiratory Pathologies - Virology and human respiratory Pathologies [CIRI] [VirPath]
Belhadi, Drifa [Auteur]
Infection, Anti-microbiens, Modélisation, Evolution [IAME (UMR_S_1137 / U1137)]
AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Peytavin, Gilles [Auteur]
Infection, Anti-microbiens, Modélisation, Evolution [IAME (UMR_S_1137 / U1137)]
AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Hites, Maya [Auteur]
Université libre de Bruxelles [ULB]
Staub, Thérèse [Auteur]
Centre Hospitalier de Luxembourg [Luxembourg] [CHL]
Greil, Richard [Auteur]
Paracelsus Medizinische Privatuniversität = Paracelsus Medical University [PMU]
Paiva, José-Artur [Auteur]
Poissy, Julien [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Peiffer-Smadja, Nathan [Auteur]
Services de Maladies Infectieuses et Tropicales [CHU Bichat]
Infection, Anti-microbiens, Modélisation, Evolution [IAME (UMR_S_1137 / U1137)]
Imperial College London
Costagliola, Dominique [Auteur]
Institut Pierre Louis d'Epidémiologie et de Santé Publique [iPLESP]
Yazdanpanah, Yazdan [Auteur]
CIC - CHU Bichat
Infection, Anti-microbiens, Modélisation, Evolution [IAME (UMR_S_1137 / U1137)]
Wallet, Florent [Auteur]
Centre Hospitalier Lyon Sud [CHU - HCL] [CHLS]
Gagneux-Brunon, Amandine [Auteur]
Centre International de Recherche en Infectiologie [CIRI]
Mentré, France [Auteur]
AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Ader, Florence [Auteur]
Université Claude Bernard Lyon 1 [UCBL]
Centre International de Recherche en Infectiologie [CIRI]
Burdet, Charles [Auteur]
Emergence de la résistance bactérienne in vivo [EA3964]
Guedj, Jérémie [Auteur]
Infection, Anti-microbiens, Modélisation, Evolution [IAME (UMR_S_1137 / U1137)]

Titre de la revue :

Journal of Antimicrobial Chemotherapy

Pagination :

1404--1412

Éditeur :

Oxford University Press (OUP)

Date de publication :

2022

ISSN :

0305-7453

Discipline(s) HAL :

Sciences du Vivant [q-bio]/Médecine humaine et pathologie

Résumé en anglais : [en]

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 ...
Lire la suite >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 (NCT 04315948; 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 (≤q7 or >7\hspace0.25emdays since symptom onset) or viral load at randomization (< or ≥q3.5 log10 copies/104 cells). Results In our model, remdesivir reduced viral production by infected cells by 2-fold on average (95% CI: 1.5\textendash 3.2-fold). Model-based simulations predict that remdesivir reduced time to viral clearance by 0.7\hspace0.25emdays compared with SoC, with large inter-individual variabilities (IQR: 0.0\textendash 1.3\hspace0.25emdays). 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\textendash 25-fold) and the median time to viral clearance by 2.4\hspace0.25emdays (IQR: 0.9\textendash 4.5\hspace0.25emdays). Conclusions Remdesivir halved viral production, leading to a median reduction of 0.7\hspace0.25emdays in the time to viral clearance compared with SoC. The efficacy was larger in patients with high viral load at randomization.Lire moins >

Langue :

Anglais

Vulgarisation :

Non

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Source :

Harvested from HAL