Many individuals living with HIV worldwide are still not receiving adequate antiretroviral therapy to prevent progression to AIDS and onward transmission, and most individuals at risk of acquiring HIV do not have access to pre-exposure prophylaxis (“PrEP”). New treatment strategies are under investigation to ease the burdens associated with long-term adherence to existing daily combination therapy, including new drugs with higher barriers to resistance, single-pill formulations, and extended release therapies with only weekly or monthly dosing. However, prioritizing these strategies for extensive clinical evaluation and understanding their impact in heterogeneous populations is difficult. In this project we are developing new multi-scale models of HIV drug action within individual patients, and using these models to optimize the development and deployment of antiretroviral therapy for the prevention and treatment of HIV. This modeling approach integrates components tracking the dynamics of virus infection and the host response, the pharmacological properties of antiretroviral drugs, and the evolution of drug resistance. It can be used to understand how treatment outcomes will change with alterations to the dose schedule, the adherence pattern, the delivery route, or co-administered drugs. In particular, we are investigating the impact of new long-acting HIV therapies and PrEP on risks of treatment failure, drug resistance, and transmission risks.