When to Initiate, When to Switch, and How to Sequence HIV Therapies: A Markov Decision Process Approach

by Shechter, Steven Michael

HIV and AIDS are major health care problems throughout the world, with 40 million people living with HIV by the end of 2005. In that year alone, 5 million people acquired HIV, and 3 million people died of AIDS. For many patients, advances in therapies over the past ten years have changed HIV from a fatal disease to a chronic, yet manageable condition. The purpose of this dissertation is to address the challenge of effectively managing HIV therapies, with a goal of maximizing a patient's total expected lifetime or quality-adjusted lifetime. Perhaps the most important issue in HIV care is when a patient should initiate therapy. Benefits of delaying therapy include avoiding the negative side effects and toxicities associated with the drugs, delaying selective pressures that induce the development of resistant strains of the virus, and preserving a limited number of treatment options. On the other hand, the risks of delayed therapy include the possibility of irreversible damage to the immune system, development of AIDS-related complications, and death. We develop a Markov decision process (MDP) model that examines this question, and we solve it using clinical data. Because of the development of resistance to administered therapies over time, an extension to the initiation question arises: when should a patient switch therapies? Also, inherent in both the initiation and switching questions is the question of which therapy to use each time. We develop MDP models that consider the switching and sequencing problems, and we discuss the challenges involved in solving these models.