Sofosbuvir/daclatasvir regimens for the treatment of COVID-19: an individual patient data meta-analysis.

Abstract

BACKGROUND:

The combination of sofosbuvir and daclatasvir has a well-established safety profile and improves clinical outcomes in HCV patients. In silico and in vitro studies suggest that sofosbuvir/daclatasvir may show antiviral activity against SARS-CoV-2.

METHODS:

Three clinical trials comparing sofosbuvir/daclatasvir-based regimens with a comparator in hospitalized COVID-19 patients were combined in a meta-analysis. The primary outcomes measured were clinical recovery within 14 days of randomization, time to clinical recovery and all-cause mortality. A two-step approach was used to analyse individual-level patient data. The individual trial statistics were pooled using the random-effects inverse-variance model.

RESULTS:

Our search identified eight studies of which three met the inclusion criteria (n = 176 patients); two studies were randomized and one was non-randomized. Baseline characteristics were similar across treatment arms. Clinical recovery within 14 days of randomization was higher in the sofosbuvir/daclatasvir arms compared with control arms [risk ratio = 1.34 (95% CI = 1.05-1.71), P = 0.020]. Sofosbuvir/daclatasvir improves time to clinical recovery [HR = 2.04 (95% CI = 1.25-3.32), P = 0.004]. The pooled risk of all-cause mortality was significantly lower in the sofosbuvir/daclatasvir arms compared with control arms [risk ratio = 0.31 (95% CI = 0.12-0.78), P = 0.013].

CONCLUSIONS:

Available evidence suggests that sofosbuvir/daclatasvir improves survival and clinical recovery in patients with moderate to severe COVID-19. However, the sample size for analysis was relatively small, one of the trials was not randomized and the designs were not standardized. These results need to be confirmed in larger randomized controlled trials.

• Authors: Bryony Simmons, Hannah Wentzel, Sara Mobarak, Gholamali Eslami, Anahita Sadeghi, Ali Ali Asgari, Hamideh Abbaspour Kasgari, Hafez Tirgar Fakheri, Shahin Merat, Andrew Hill
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 76 Issue 2 Pg. 286-291 (01 19 2021) ISSN: 1460-2091 [Electronic] England
• PMID: 33063117 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Antiviral Agents
• Carbamates
• Imidazoles
• Pyrrolidines
• Valine
• daclatasvir
• Sofosbuvir

Topics

• Adult
• Aged
• Antiviral Agents (administration & dosage, therapeutic use)
• Carbamates (administration & dosage, therapeutic use)
• Drug Therapy, Combination
• Female
• Humans
• Imidazoles (administration & dosage, therapeutic use)
• Iran
• Male
• Middle Aged
• Pyrrolidines (administration & dosage, therapeutic use)
• Randomized Controlled Trials as Topic
• SARS-CoV-2
• Severity of Illness Index
• Sofosbuvir (administration & dosage, therapeutic use)
• Treatment Outcome
• Valine (administration & dosage, analogs & derivatives, therapeutic use)
• COVID-19 Drug Treatment