Modeling Influenza Antiviral Strategies: Reducing Burden and Preventing Resistance

Area of Science:

• Epidemiology
• Infectious Diseases
• Pharmacology

Background:

• Influenza epidemics cause significant global mortality and morbidity.
• Antiviral drugs like baloxavir and oseltamivir are crucial for managing influenza.
• Widespread antiviral use raises concerns about the emergence of drug-resistant influenza strains, especially in vulnerable populations.

Purpose of the Study:

• To evaluate age-stratified antiviral treatment strategies for influenza.
• To assess the impact of different strategies on reducing illness (measured by DALYs lost) and the risk of antiviral resistance.
• To compare the effectiveness and resistance risks of baloxavir versus oseltamivir, and explore combination therapy.

Main Methods:

• Development and application of a data-driven, age-stratified mathematical model.
• Simulation of various antiviral treatment scenarios during a typical US influenza season.
• Quantification of disability-adjusted life-years (DALYs) lost and the probability of widespread antiviral resistance transmission.

Main Results:

• Administering baloxavir to 20% of symptomatic individuals >5 years old reduced DALYs by 32.3% but carried a 26.4% risk of widespread resistance.
• Using oseltamivir for the same population reduced DALYs by 19.5% with only a 5.4% risk of resistance.
• Combination baloxavir-oseltamivir therapy for the same group reduced DALYs by 33.5% with a 10.2% risk of resistance.

Conclusions:

• Baloxavir offers greater DALY reduction than oseltamivir but at a significantly higher risk of resistance.
• Combination therapy presents a promising strategy to maximize DALY reduction while mitigating resistance risks.
• Implementing adaptive strategies, such as suspending baloxavir use upon resistance detection or using combination therapy, can effectively manage influenza and curb resistance spread.