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Cited by 550Influenza Virus Research StudiesRespiratory viral infections researchBacterial Infections and Vaccines

The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.

Use of the Oral Neuraminidase Inhibitor Oseltamivir in Experimental Human Influenza: Randomized Controlled Trials for Prevention and Treatment

Hayden, Frederick G., Treanor, John J., Fritz, R. Scott, Lobo, Monica, Betts, Robert F., Miller, Madeline, Kinnersley, Nelson, Mills, Roger G., Ward, Penelope, Straus, Stephen E.·1999·JAMA
DOI 10.1001/jama.282.13.1240
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Abstract

CONTEXT: Influenza virus neuraminidase is thought to be essential for virus replication in humans; however, to date, available neuraminidase inhibitors are limited to zanamivir, which is topically administered. OBJECTIVE: To determine the safety, tolerability, and antiviral activity of oral neuraminidase inhibitor oseltamivir (GS4104/Ro64-0796) for prevention and the early treatment of influenza in experimentally infected humans. DESIGN: Two randomized, double-blind, placebo-controlled trials conducted between June and July 1997. SETTING: Individual hotel rooms; 2 large US university medical schools. PARTICIPANTS: A total of 117 healthy adult volunteers (aged 18-40 years; median age, 21 years) who were susceptible (hemagglutination-inhibition antibody titer < or =1:8). INTERVENTIONS: All subjects were inoculated intranasally with influenza A/Texas/36/91 (H1N1) virus. For the prophylaxis study, oral oseltamivir (100 mg once daily [n = 12], 100 mg twice daily [n = 12], or matching placebo [n = 13], starting 26 hours before virus inoculation) was administered. For the treatment study, the same drug was given (20 mg, 100 mg, or 200 mg twice daily, 200 mg once daily, or matching placebo [n = 16], in each group starting 28 hours after inoculation). All regimens were continued for 5 days. MAIN OUTCOME MEASURES: Comparing placebo groups with pooled treatment groups, for prophylaxis, outcomes included frequency of infection and viral shedding; for treatment, viral shedding in titers. RESULTS: In the prophylaxis study, 8 (67%) of 12 placebo and 8 (38%) of 21 oseltamivir recipients became infected (P = .16; efficacy, 61%); 6 (50%) placebo compared with 0 oseltamivir recipients shed virus (P<.001; efficacy, 100%), and 33% of placebo but no oseltamivir recipient had infection-related respiratory illness (P<.01). Among infected subjects in the treatment study (n = 69), the viral titer area under the curve of the combined oseltamivir groups (n = 56) was lower (median [interquartile range [IQR]], 80 [23-151] vs 273 [79-306] log10 tissue culture-infective doses50 per milliliter x hour; P = .02) than the placebo group (n = 13), and the median (IQR) duration of viral shedding with therapy was reduced from 107 (83-131) to 58 (35-59) hours (P = .003). Oseltamivir treatment also reduced symptom scores (median [IQR] score-hours, 225 [97-349] vs 400 [189-645]; P = .05), and nasal proinflammatory cytokine levels. Transient mild to moderate nausea after dosing was observed in 15 (17%) of 88 oseltamivir and 2 (7%) of 29 placebo recipients (95% confidence interval for difference, -11% to 68%), which was largely prevented by ingestion with food. CONCLUSIONS: In these trials, prophylaxis and early treatment with oral oseltamivir were both associated with significant antiviral and clinical effects in experimental human influenza.

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Authors
Hayden, F. G., Treanor, J. J., Fritz, R. S., Lobo, M., Betts, R. F., Miller, M., Kinnersley, N., Mills, R. G., Ward, P., & Straus, S. E.
Affiliations
University of Virginia (US)
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
1999-10-06
Volume
282
Issue
13
Pages
1240
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.282.13.1240
OpenAlex
W2072658090
Cited by
550
References
30
Citations by year
2026: 10 · 2025: 11 · 2024: 8 · 2023: 10 · 2022: 17 · 2021: 14 · 2020: 17 · 2019: 8 · 2018: 12 · 2017: 16 · 2016: 22 · 2015: 13 · 2014: 23 · 2013: 22 · 2012: 22
FWCI
30.45
Type
journal article
Language
en
Open access
closed
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (n01co056000-057)
  • National Cancer Institute (N01 CO 56000)
Topics
  • Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
  • Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
  • Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
Keywords
oseltamivir, neuraminidase inhibitors, influenza A virus, antiviral prophylaxis, antiviral therapy, viral shedding, H1N1 influenza, drug safety and tolerability, dose comparison, zanamivir, influenza C, influenza D virus, influenza E
MeSH terms
Administration, Oral, Adolescent, Adult, Amines, Dose-Response Relationship, Drug, Double-Blind Method, Enzyme Inhibitors, Female, Humans, Influenza, Human, Male, Nausea, Neuraminidase, Nose, Influenza A virus, Area Under Curve, Oseltamivir

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