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- Title
Effect of remdesivir on viral dynamics in COVID-19 hospitalized patients: a modelling analysis of the randomized, controlled, open-label DisCoVeRy trial.
- Authors
Lingas, Guillaume; Néant, Nadège; Gaymard, Alexandre; Belhadi, Drifa; Peytavin, Gilles; Hites, Maya; Staub, Thérèse; Greil, Richard; Paiva, Jose-Artur; Poissy, Julien; Peiffer-Smadja, Nathan; Costagliola, Dominique; Yazdanpanah, Yazdan; Wallet, Florent; Gagneux-Brunon, Amandine; Mentré, France; Ader, Florence; Burdet, Charles; Guedj, Jérémie; Bouscambert-Duchamp, Maude
- Abstract
<bold>Background: </bold>The antiviral efficacy of remdesivir in COVID-19 hospitalized patients remains controversial.<bold>Objectives: </bold>To estimate the effect of remdesivir in blocking viral replication.<bold>Methods: </bold>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 >7 days since symptom onset) or viral load at randomization (< or ≥3.5 log10 copies/104 cells).<bold>Results: </bold>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 0.7 days compared with SoC, with large inter-individual variabilities (IQR: 0.0-1.3 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 2.4 days (IQR: 0.9-4.5 days).<bold>Conclusions: </bold>Remdesivir halved viral production, leading to a median reduction of 0.7 days in the time to viral clearance compared with SoC. The efficacy was larger in patients with high viral load at randomization.
- Subjects
REMDESIVIR; VIRAL load; VIRAL replication; HOSPITAL patients
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2022, Vol 77, Issue 5, p1404
- ISSN
0305-7453
- Publication type
Journal Article
- DOI
10.1093/jac/dkac048