Trial reportThe Journal of infectious diseases2023
Viral Resistance Analyses From the Remdesivir Phase 3 Adaptive COVID-19 Treatment Trial-1 (ACTT-1).
Trial report in The Journal of infectious diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04280705 (A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults), which is not on this map. Cited by 26 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults
Who cites it
26 citing papers in PubMed, 30 citations in OpenAlex.
- Virologic insights from the phase 3 REDPINE trial: remdesivir in renally impaired and immunocompromised patients with COVID-19.Antimicrobial agents and chemotherapy · 2026Trial
- SARS-CoV-2 resistance analyses from the Phase 3 PINETREE study of remdesivir treatment in nonhospitalized participants.Antimicrobial agents and chemotherapy · 2025Trial
- No Remdesivir Resistance Observed in the Phase 3 Severe and Moderate COVID-19 SIMPLE Trials.Viruses · 2024Trial
- Article
- Cross-resistance patterns in SARS-CoV-2 against 3CL protease inhibitors.Nature communications · 2026Article
- Preferential remdesivir triphosphate incorporation by SARS-CoV-2 polymerase is altered to ATP by the S759A mutation.Communications biology · 2026Article
- Article
- Role of remdesivir for the treatment of COVID-19 in patients with hematologic malignancy-A narrative review and expert opinion.European journal of clinical investigation · 2025Review
- Structural basis for selective remdesivir incorporation by SARS-CoV-2 polymerase, and S759A resistance.Research square · 2025Article
- Review
- Review
- SARS-CoV-2 Remdesivir Exposure Leads to Different Evolutionary Pathways That Converge in Moderate Levels of Drug Resistance.Viruses · 2025Article
- Remdesivir postexposure prophylaxis limits measles-induced "immune amnesia" and measles antibody responses in macaques.JCI insight · 2025Article
- Remdesivir and Obeldesivir Retain Potent Antiviral Activity Against SARS-CoV-2 Omicron Variants.Viruses · 2025Article
- The impact of remdesivir on SARS-CoV-2 evolution in vivo.JCI insight · 2025Article
- Oral pharmacokinetics and efficacy of oral phospholipid remdesivir nucleoside prodrugs against SARS-CoV-2 in mice.Antimicrobial agents and chemotherapy · 2024Article
- Article
- Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections.Nature communications · 2024Article
- COVID-19 and Cancer Care: A Review and Practical Guide to Caring for Cancer Patients in the Era of COVID-19.Current oncology (Toronto, Ont.) · 2024Review
- SARS-CoV-2 Resistance to Small Molecule Inhibitors.Current clinical microbiology reports · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundRemdesivir is approved for treatment of coronavirus disease 2019 (COVID-19) in nonhospitalized and hospitalized adult and pediatric patients. Here we present severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resistance analyses from the phase 3 ACTT-1 randomized placebo-controlled trial conducted in adult participants hospitalized with COVID-19.
methodsSwab samples were collected at baseline and longitudinally through day 29. SARS-CoV-2 genomes were sequenced using next-generation sequencing. Phenotypic analysis was conducted directly on participant virus isolates and/or using SARS-CoV-2 subgenomic replicons expressing mutations identified in the Nsp12 target gene.
resultsAmong participants with both baseline and postbaseline sequencing data, emergent Nsp12 substitutions were observed in 12 of 31 (38.7%) and 12 of 30 (40.0%) participants in the remdesivir and placebo arms, respectively. No emergent Nsp12 substitutions in the remdesivir arm were observed in more than 1 participant. Phenotyping showed low to no change in susceptibility to remdesivir relative to wild-type Nsp12 reference for the substitutions tested: A16V (0.8-fold change in EC50), P323L + V792I (2.2-fold), C799F (2.5-fold), K59N (1.0-fold), and K59N + V792I (3.4-fold).
conclusionsThe similar rate of emerging Nsp12 substitutions in the remdesivir and placebo arms and the minimal change in remdesivir susceptibility among tested substitutions support a high barrier to remdesivir resistance development in COVID-19 patients. Clinical Trials Registration. NCT04280705.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.