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Individualized, model-based, target-oriented optimal concentration-controlled dosing of HIV medications can be beneficial to patients for whom there are limited dosing guidelines, such as children, adolescents, or patients with altered physiologic function. Barriers to this approach include lack of training, expertise, and access to appropriate software to assist the clinician. The authors present 4 illustrative clinical cases of HIV-infected patients whose therapy was optimized using population pharmacokinetic models (here generated from published studies) and supplemented by individualized Bayesian adaptive control of dosage regimens as implemented in the MM-USCPACK software. These 4 cases illustrate how clinicians can maximize therapeutic success in (1) patients with reduced drug clearance, (2) young adolescents transitioning to adult physiology, (3) patients with dose-dependent toxicity, and (4) adolescents with limited therapeutic options.