Assessing the oseltamivir-induced resistance risk and implications for influenza infection control strategies
Nan-Hung Hsieh1, Yi-Jun Lin2, Ying-Fei Yang2
1Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA.
Background:
Oseltamivir-resistant mutants with higher drug resistance rates and low trans-mission fitness costs have not accounted for influenza (sub)type viruses. Predicting the impacts of neuraminidase inhibitor therapy on infection rates and transmission of drug-resistant viral strains requires further investigation.
Objectives:
The purpose of this study was to assess the potential risk of oseltamivir-induced resistance for influenza A (H1N1) and A (H3N2) viruses.
Materials And Methods:
An immune-response-based virus dynamic model was used to best fit the oseltamivir-resistant A (H1N1) and A (H3N2) infection data. A probabilistic risk assessment model was developed by incorporating branching process-derived probability distribution of resistance to estimate oseltamivir-induced resistance risk.
Results:
Mutation rate and sensitive strain number were key determinants in assessing resistance risk. By increasing immune response, antiviral efficacy, and fitness cost, the spread of resistant strains for A (H1N1) and A (H3N2) were greatly decreased. Probability of resistance depends most strongly on the sensitive strain number described by a Poisson model. Risk of oseltamivir-induced resistance increased with increasing the mutation rate for A (H1N1) only. The ≥50% of resistance risk induced by A (H1N1) and A (H3N2) sensitive infected cells were 0.4 (95% CI: 0.28-0.43) and 0.95 (95% CI 0.93-0.99) at a mutation rate of 10-6, respectively. Antiviral drugs must be administrated within 1-1.5 days for A (H1N1) and 2-2.5 days for A (H3N2) virus infections to limit viral production.
Conclusion:
Probabilistic risk assessment of antiviral drug-induced resistance is crucial in the decision-making process for preventing influenza virus infections.
Insights
Assessing oseltamivir resistance risk in influenza A (H1N1) and A (H3N2) is vital. Early antiviral treatment and understanding mutation rates are key to mitigating the spread of drug-resistant influenza strains.
Area of Science:
- Virology
- Epidemiology
- Computational Biology
Background:
- Oseltamivir resistance in influenza poses a public health threat, particularly for strains with low fitness costs.
- Predicting the impact of neuraminidase inhibitor therapy on drug-resistant influenza transmission requires further study.
Purpose of the Study:
- To evaluate the risk of oseltamivir-induced resistance in influenza A (H1N1) and A (H3N2) viruses.
- To inform strategies for managing antiviral resistance in seasonal influenza.
Main Methods:
- Developed an immune-response-based virus dynamic model to analyze oseltamivir-resistant influenza A (H1N1) and A (H3N2) infection data.
- Utilized a probabilistic risk assessment model incorporating branching process theory to estimate resistance risk.
Main Results:
- Mutation rate and susceptible strain numbers are critical factors in determining resistance risk.
- Increased immune response, antiviral efficacy, and fitness costs significantly reduced the spread of resistant strains.
- The probability of resistance was strongly influenced by the number of susceptible strains, modeled using a Poisson distribution. Risk of resistance increased with mutation rate for A (H1N1).
- Optimal antiviral administration times were identified: within 1-1.5 days for A (H1N1) and 2-2.5 days for A (H3N2) to limit viral production.
Conclusions:
- Probabilistic risk assessment is essential for informed decision-making in preventing antiviral drug-induced resistance.
- Effective management of influenza requires understanding and predicting resistance dynamics to guide therapeutic interventions.
