Effect of Remdesivir on Viral Dynamics in COVID-19 Hospitalized Patients: A Modelling Analysis of the Randomized, Controlled, Open-Label DisCoVeRy Trial - Sorbonne Université Access content directly
Journal Articles Journal of Antimicrobial Chemotherapy Year : 2022

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

Abstract

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.

Dates and versions

hal-03793485 , version 1 (01-10-2022)

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Maude Bouscambert-Duchamp, Guillaume Lingas, Nadège Néant, Alexandre Gaymard, Drifa Belhadi, et al.. Effect of Remdesivir on Viral Dynamics in COVID-19 Hospitalized Patients: A Modelling Analysis of the Randomized, Controlled, Open-Label DisCoVeRy Trial. Journal of Antimicrobial Chemotherapy, 2022, 77 (5), pp.1404--1412. ⟨10.1093/jac/dkac048⟩. ⟨hal-03793485⟩
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