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Treatment-Emergent Influenza Variant Viruses With Reduced Baloxavir Susceptibility: Impact on Clinical and Virologic Outcomes in Uncomplicated Influenza.
- Source :
- Journal of Infectious Diseases; 2/1/2020, Vol. 221 Issue 3, p346-355, 10p
- Publication Year :
- 2020
-
Abstract
- <bold>Background: </bold>Single-dose baloxavir rapidly reduces influenza virus titers and symptoms in patients with uncomplicated influenza, but viruses with reduced in vitro susceptibility due to amino acid substitutions at position 38 of polymerase acidic protein (PA/I38X) sometimes emerge.<bold>Methods: </bold>We evaluated the kinetics, risk factors, and effects on clinical and virologic outcomes of emergence of PA/I38X-substituted viruses.<bold>Results: </bold>Viruses containing PA/I38X substitutions were identified 3-9 days after baloxavir treatment in 9.7% (36/370) of patients, of whom 85.3% had transient virus titer rises. Median time to sustained cessation of infectious virus detection was 192, 48, and 96 hours in the baloxavir recipients with PA/I38X-substituted viruses, without PA/I38X-substituted viruses, and placebo recipients, respectively. The corresponding median times to alleviation of symptoms were 63.1, 51.0, and 80.2 hours, respectively. After day 5, symptom increases occurred in 11.5%, 8.0%, and 13.0%, respectively, and in 8.9% of oseltamivir recipients. Variant virus emergence was associated with lower baseline neutralizing antibody titers.<bold>Conclusions: </bold>The emergence of viruses with PA/I38X substitutions following baloxavir treatment was associated with transient rises in infectious virus titers, prolongation of virus detectability, initial delay in symptom alleviation, and uncommonly with symptom rebound. The potential transmissibility of PA/I38X-substituted viruses requires careful study.<bold>Clinical Trial Registration: </bold>NCT02954354. [ABSTRACT FROM AUTHOR]
- Subjects :
- INFLUENZA viruses
AMINO acids
INFLUENZA
SULFUR compounds
PYRIDINE
RESEARCH
HETEROCYCLIC compounds
VIRAL load
RESEARCH methodology
ANTIVIRAL agents
EVALUATION research
MEDICAL cooperation
TREATMENT effectiveness
COMPARATIVE studies
BLIND experiment
DRUG resistance in microorganisms
INFLUENZA A virus, H3N2 subtype
OSELTAMIVIR
PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 00221899
- Volume :
- 221
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Journal of Infectious Diseases
- Publication Type :
- Academic Journal
- Accession number :
- 141288124
- Full Text :
- https://doi.org/10.1093/infdis/jiz244