Portal de investigação
Effect of remdesivir on viral dynamics in COVID-19 hospitalized patients: a modelling analysis of the randomized, controlled, open-label DisCoVeRy trial
Data de publicação:
Data Ahead of Print:
Autores da FMUP
Participantes de fora da FMUP
- Lingas, G
- Neant, N
- Gaymard, A
- Belhadi, D
- Peytavin, G
- Hites, M
- Staub, T
- Greil, R
- Poissy, J
- Peiffer-Smadja, N
- Costagliola, D
- Yazdanpanah, Y
- Wallet, F
- Gagneux-Brunon, A
- Mentre, F
- Ader, F
- Burdet, C
- Guedj, J
- Bouscambert-Duchamp, M
- DisCoVeRy Study Grp
Unidades de investigação
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 (<= 7 or >7 days since symptom onset) or viral load at randomization (< or >= 3.5 log(10) copies/10(4) 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 0.7 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). Conclusions 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.
Dados da publicação
- ISSN/ISSNe:
- 0305-7453, 1460-2091
- Tipo:
- Article
- Páginas:
- 1404-1412
- DOI:
- 10.1093/jac/dkac048
- Link para outro recurso:
- www.scopus.com
Journal of Antimicrobial Chemotherapy Oxford University Press
Citações Recebidas na Web of Science: 23
Citações Recebidas na Scopus: 29
Documentos
- Não há documentos
Filiações
Keywords
- Adenosine Monophosphate; Alanine; Antiviral Agents; COVID-19; Humans; SARS-CoV-2; remdesivir; adenosine phosphate; alanine; antivirus agent; remdesivir; adult; aged; antiviral activity; Article; controlled study; coronavirus disease 2019; female; health care quality; hospital patient; human; major clinical study; male; mathematical model; nasopharyngeal swab; open study; plots and curves; randomized controlled trial; viral clearance; virus load; virus replication; drug therapy
Financiamento
Proyectos asociados
The impact of the Covid-19 pandemic on antimicrobial consumption: a descriptive and correlation analysis in a tertiary care hospital in Portugal
Investigador Principal: José Artur Osório de Carvalho Paiva
Estudo Clínico Académico (Antimicrobial consumpti) . 2021
Citar a publicação
Lingas G,Neant N,Gaymard A,Belhadi D,Peytavin G,Hites M,Staub T,Greil R,Paiva JA,Poissy J,Peiffer N,Costagliola D,Yazdanpanah Y,Wallet F,Gagneux A,Mentre F,Ader F,Burdet C,Guedj J,Bouscambert M,DisCoVeRy GRP. 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. 2022. 77. (5):p. 1404-1412. IF:5,200. (1).
