Numerical approaches for the rapid analysis of prophylactic efficacy against HIV with arbitrary drug-dosing schemes

Pre-exposure prophylaxis (PrEP) is an important pillar to prevent HIV  transmission. Because of experimental and clinical shortcomings, mathematical models that integrate pharmacological, viral- and host factors are frequently used to quantify clinical efficacy of PrEP. Stochastic simulations of these models provides sample statistics from which the clinical efficacy is approximated. However, many stochastic simulations are needed to reduce the associated sampling error. To remedy the shortcomings of stochastic simulation, we developed three numerical methods that allow predicting the efficacy of arbitrary prophylactic regimen directly from a viral dynamics model, without sampling. We apply the methods to various hypothetical dolutegravir (DTG) prophylaxis scenarios. The approaches are verified against one another, as well as state-of-the-art stochastic simulation. While the methods are more accurate than stochastic simulation, they are superior in terms of computational performance. For example, a continuous 6-month prophylactic profile is computed within a few seconds on a laptop computer. The methods9 computational performance, therefore, substantially expands the horizon of feasible analysis in the context of PrEP, and possibly other applications.