Evidence map›Paper›PMID 38716969›Full record

Trial reportThe Journal of infectious diseases2024

Characterization of Treatment Resistance and Viral Kinetics in the Setting of Single-Active Versus Dual-Active Monoclonal Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2.

Manish C Choudhary, Rinki Deo, Teresa H Evering, Kara W Chew, Mark J Giganti, Carlee Moser, Justin Ritz, James Regan, James P Flynn, Charles R Crain and 12 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in The Journal of infectious diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Trial
  2. Trial
  3. Article
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  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Manish C ChoudharyDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Rinki DeoDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Teresa H EveringDepartment of Medicine, Weill Cornell Medicine, New York, New York, USA.
Kara W ChewDepartment of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Mark J GigantiDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.ORCID 0000-0003-2255-9756
Carlee MoserDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.ORCID 0000-0001-5601-9112
Justin RitzDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
James ReganDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
James P FlynnDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Charles R CrainDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
David Alain WohlDepartment of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.
Judith S CurrierDepartment of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Joseph J EronDepartment of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.
David MargolisBrii Biosciences, Durham, North Carolina, USA.
Qing ZhuBrii Biosciences, Durham, North Carolina, USA.
Lijie ZhonBrii Biosciences, Durham, North Carolina, USA.
Li YaBrii Biosciences, Durham, North Carolina, USA.
Alexander L GreningerDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.ORCID 0000-0002-7443-0527
Michael D HughesDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Davey SmithDepartment of Medicine, University of California, San Diego, La Jolla, California, USA.
Eric S DaarDepartment of Medicine, Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, USA.
Jonathan Z LiDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0001-9914-9662

Funding

Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/UM1AI068636 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, RAJESH T GANDHI · 2011 to 2026
$1073.1M
Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marlene Ann Cooper, Michael David Hughes · 2011 to 2026
$246.6M
Validation, CLIA and Qualification (VQC): Enhancing the RS ratio as a tool for AIDS Clinical Trial Group (ACTG) tuberculosis trialsUM1AI106701 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Grace M Aldrovandi · 2014 to 2026
$116.8M
University of North Carolina Global HIV Prevention and Treatment Clinical Trials Unit 2024 SupplementUM1AI069423 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, MINA CHRISTINE HOSSEINIPOUR · 2012 to 2026
$71.8M
UCLA AIDS Prevention and Treatment Clinical Trials UnitUM1AI069424 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Judith S. Currier, RAPHAEL J LANDOVITZ · 2012 to 2026
$51.8M
Weill Cornell Medicine - Rutgers New Jersey Medical School Clinical Trials UnitUM1AI069419 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI ROY M. GULICK · 2012 to 2026
$44.6M
Seattle Vaccine Trials UnitUM1AI069481 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Rachel Ann Bender Ignacio, Margaret Juliana McElrath · 2012 to 2026
$24.4M
National Institute of Allergy and Infectious DiseasesNIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI069419NIAID NIH HHS UM1 AI069423NIAID NIH HHS UM1 AI069424NIAID NIH HHS UM1 AI069481NIAID NIH HHS UM1 AI106701NIH HHS UM1AI068634
6 · The paper itself

Abstract

backgroundMonoclonal antibodies (mAbs) represent a crucial antiviral strategy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether combination mAbs offer a benefit over single-active mAb treatment. Amubarvimab and romlusevimab significantly reduced the risk of hospitalizations or death in the ACTIV-2/A5401 trial. Certain SARS-CoV-2 variants are intrinsically resistant against romlusevimab, leading to only single-active mAb therapy with amubarvimab in these variants. We evaluated virologic outcomes in individuals treated with single- versus dual-active mAbs.

methodsParticipants were nonhospitalized adults at higher risk of clinical progression randomized to amubarvimab plus romlusevimab or placebo. Quantitative SARS-CoV-2 RNA levels and targeted S-gene next-generation sequencing was performed on anterior nasal samples. We compared viral load kinetics and resistance emergence between individuals treated with effective single- versus dual-active mAbs depending on the infecting variant.

resultsStudy participants receiving single- or dual-active mAbs had similar demographics, baseline nasal viral load, symptom score, and symptom duration. Compared with single-active mAb treatment, treatment with dual-active mAbs led to faster viral load decline at study days 3 (P < .001) and 7 (P < .01). Treatment-emergent resistance mutations were more likely to be detected after amubarvimab plus romlusevimab treatment than with placebo (2.6% vs 0%; P < .001) and were more frequently detected in the setting of single-active compared with dual-active mAb treatment (7.3% vs 1.1%; P < .01). Single-active and dual-active mAb treatment resulted in similar decrease in rates of hospitalizations or death.

conclusionsCompared with single-active mAb therapy, dual-active mAbs led to similar clinical outcomes but significantly faster viral load decline and a lower risk of emergent resistance.

Indexed as

Antibodies, Monoclonal, HumanizedCOVID-19 Drug TreatmentSARS-CoV-2Viral LoadAdultAgedAntibodies, MonoclonalAntiviral AgentsCOVID-19Drug Resistance, ViralDrug Therapy, CombinationFemaleHumansMaleMiddle AgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntiviral AgentsmAb resistanceSARS-CoV-2variantsviral kinetics

Identifiers

PMID38716969
PMCPMC11326811

What OpenQuestion holds

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Registered trials

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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.