Core B: Computational

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Project Summary for Mathematical Modeling and Bioinformatics Core The goal of this Core is to provide mathematical modeling and bioinformatics support for the three research projects. We have assembled a team of experts with experience in modeling HIV viral dynamics, the effects of antiretroviral therapy, the establishment of the HIV reservoir, and the effects of latency reversing agents on the reservoir and on the time to viral load rebound after ART termination. We also have experience in developing models of post-treatment control. In addition, we have experience in HIV sequence analysis and bioinformatics that will allow us to gain information from rebounding virus. Our technical expertise includes working with deterministic and stochastic models as well as in the development of simulation models. We have proven capabilities in fitting models to data, estimating parameters, parameter sensitivity analysis, parameter identification, pharmacokinetics, pharmacodynamics, pharmacometrics and biostatistics. Team members not only have modeling experience but have also worked with the three project PIs in the past and have good working relationships. The Core also has superb computing resources available through Los Alamos National Laboratory. The models to be developed by the Core will address strategies for cure or viral remission in pediatric and adult cases of HIV as well as in nonhuman primates infected with SIV. The models will provide a basis for synergy between the various projects, where information learned from models in one arena can inform models in another area. For example, models of pediatric patients with immature immune systems, when compared with model results for HIV-infected adults, may provide information about the role of more developed immune responses in HIV control. Models of the effects of checkpoint inhibitors and latency reversing agents in nonhuman primates may inform on the effects of immune modulators in HIV infected children and adults. Thus, through modeling we foresee integrating information obtained from all three research projects to benefit the overall goal of achieving viral remission or cure.