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We present an overview of some concepts and methodologies we believe useful in modeling HIV pathogenesis. After a brief discussion of motivation for and previous efforts in the development of mathematical models for progression of HIV infection and treatment, we discuss mathematical and statistical ideas relevant to Structured Treatment Interruptions (STI). Among these are model development and validation procedures including parameter estimation, data reduction and representation, and optimal control relative to STI. Results from initial attempts in each of these areas by an interdisciplinary team of applied mathematicians, statisticians and clinicians are presented.