Modeling viral shedding and symptom outcomes in oseltamivir-treated experimental influenza infection

Abstract

Influenza remains a global public health concern, and although the antiviral drug oseltamivir is widely used to treat infections, questions regarding its actual antiviral efficacy and clinical benefits remain. Here, we evaluated the effects of oseltamivir on viral shedding dynamics in the context of experimental influenza infection. We analyzed individual participant data, including viral load, time to symptom alleviation, and laboratory test measurements, obtained from three publicly available clinical trials involving experimental infections with influenza A and B viruses. We applied mathematical modeling and estimated parameters using a nonlinear mixed-effects model to capture viral infection dynamics. Our analysis revealed that, compared with placebo groups, the oseltamivir-treated groups tended to have lower values in terms of viral load area under the curve, duration of infection, peak viral titer, and time to peak; however, most of these differences were not significant; and no dose-dependent effects were observed. Moreover, there was no significant correlation between time to symptom alleviation and viral load. Some laboratory test parameters showed opposing correlations with symptom-related and viral load-related outcomes. These findings are consistent with distinct mechanisms underlying the symptom-alleviating effects of oseltamivir and its antiviral activity. Our findings suggest that the availability of individual-level data for public use is essential because it enables the evaluation of mechanisms in clinical trials and the development of more appropriate outcome measures.