Fig 1.
Summary of data obtained from oseltamivir clinical trials.
(A) Flowchart of participant selection per analysis. Data from participants who met the criteria among data used for efficacy analysis in the human challenge were used for analysis of viral load and correlation analysis using laboratory data. (B) Distribution of sex (left), age (center), and dosing (right) by genotype in the analyzed population. (C) Summary of laboratory measurements and temperature values by genotype. Statistical significance was determined using a two-tailed Welch’s t-test. p-values are nominal and not adjusted for multiple comparisons.
Fig 2.
Quantification of the influenza virus A and B loads.
(A) Dynamics of the viral load after virus inoculation by genotype estimated for individual participants in the oseltamivir-treated (colored) and placebo-treated (gray) groups. The solid and bold black lines represent the population estimates of viral load dynamics. The underlying data and individual fits are shown in S2 Fig. (B) AUC (left) and duration of virus shedding (right) for influenza A (red) and B (blue) infection compared with previous studies by Hooker and Ganusov [39]. (C) Comparison of the estimated characteristics of virus dynamics between groups by dose of oseltamivir for influenza A (left) and B (right) viruses. The doses without “od” were administered twice daily; the dose with “od” was administered once daily. We adjusted p-values according to the number of group combinations using a post hoc Bonferroni correction.
Fig 3.
Relationship between time to alleviation and viral infection dynamics.
(A) Kaplan–Meier survival curves describing the time to alleviation changes for each dose of the oseltamivir treatment group. The doses without “od” were administered twice daily; the dose with “od” was administered once daily. Statistical significance was determined using the log-rank test. p-values are nominal and not adjusted for multiple comparisons. (B and C) Correlations between daily viral load (B) or viral load-related features (C) were calculated using a mathematical model using estimated individual parameters and time to alleviate influenza A (red) and B (blue). Each point represents the value obtained from an individual participant.
Fig 4.
Correlations between participant status and outcomes.
(A) Relationships between the time to alleviate composite symptoms and laboratory measurements and body temperature (upper half) and between the AUC and laboratory measurements (lower half). (B) Partial rank correlation coefficients of participant background and clinical measurements against time to alleviation, AUC, peak virus titer, and duration of infection.