HIV presents special therapeutic challenges to the drug development team, including resistance, complex pharmacokinetics, and patient compliance. Our modeling and simulation approach in HIV, as in other therapeutic domains, is to integrate relevant sub-models, estimate key parameters from trial data, and simulate candidate trial designs. The business benefits can include optimizing the design of the next trial or sequence of trials, better go/no-go decisions, and strategies to optimize unavoidable tradeoffs such as that between patient compliance and difficult dosing. Shawn O'Connor