Presentation Information
[SS21-05]Modeling Resistance Evolution in HIV under Long-Acting PrEP: A Darwinian Approach
*Yeona Kang1, Yanping Ma2, Katharine Gurski (1. Howard University (United States of America), 2. Loyola Marymount University (United States of America))
Keywords:
HIV1,Resistance evolution
The emergence of drug-resistant HIV during long-acting pre-exposure prophylaxis (PrEP) poses a significant challenge to current prevention strategies. This paper develops a Darwinian model based on evolutionary game theory (EGT) to explore the dynamics of resistance evolution in early HIV infection under cabotegravir long-acting (CAB-LA) PrEP. We integrate within-host cellular models of HIV replication with evolutionary dynamics to analyze how viral fitness and resistance evolve in the presence of two transmission modes—free virion transfer and cell-to-cell transfer. The model incorporates pharmacokinetics and pharmacodynamics of CAB-LA to evaluate the trade-off between viral infectivity and resistance development.
Our findings show that cell-to-cell transmission significantly enhances the spread of resistant strains compared to free virion transfer, suggesting that viral strategies for infection play a critical role in resistance dynamics. Sensitivity analysis highlights the importance of drug effectiveness and viral evolutionary speed in determining resistance outcomes. The results underscore the need for optimized dosing protocols and suggest that targeting cell-to-cell transmission may improve the efficacy of long-acting PrEP strategies. This work provides a framework for predicting resistance evolution and offers insights for designing more effective HIV prevention approaches.
Our findings show that cell-to-cell transmission significantly enhances the spread of resistant strains compared to free virion transfer, suggesting that viral strategies for infection play a critical role in resistance dynamics. Sensitivity analysis highlights the importance of drug effectiveness and viral evolutionary speed in determining resistance outcomes. The results underscore the need for optimized dosing protocols and suggest that targeting cell-to-cell transmission may improve the efficacy of long-acting PrEP strategies. This work provides a framework for predicting resistance evolution and offers insights for designing more effective HIV prevention approaches.