STRATEGIC MANAGEMENT OF ANTIRETROVIRALS IN HIV INFECTION

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Over the last 2 years there have been dramatic advances in the treatment of HIV infection. The availability of protease inhibitors and non-nucleoside reverse transcriptase inhibitors allowed the development of combinations of antiretroviral drugs (HAART) that can completely block HIV viral replication. The use of highly active antiretroviral therapy has dramatically changed the morbidity and mortality rates of HIV infection and AIDS. This progress is not without problems. Protease inhibitors have major toxicities that are only partially understood. They are difficult to take requiring tight schedules and dietary restrictions and they are expensive. Better strategies in the use of these drugs are needed in order to maximize clinical benefits and improve the quality of life of patients. Given the fact that large strategic trials of many different combinations are not feasible, it is essential to determine if alternative strategic approaches can be developed. Two possible options constitute the proposed research in this grant: a)the use of statistical methods such as decision analysis to guide treatment decisions, and b) use of small pilot studies to provide basis for supporting or rejecting hypothesis that can guide strategic decisions. To accomplish these aims the investigator will: 1) Perfrom computing modeling of different strategies in the management of antiretroviral therapy in HIV infected patients using decision analysis techniques as well as Markov models; 2) Evaluate whether a fully suppressive antiretroviral regimen containing a protease inhibitor can be simplified substituting the protease inhibitor with a non-nucleoside reverse transcriptase inhibitor (NNRTI). He will also determine whether this simplification strategy has additional pathophysiologic effects correcting the metabolic abnormalities associated with protease inhibitor therapy, changing the body composition of the patients as measured by DEXA (dual energy x-ray absorptiometry) scans, or changing the distribution and absolute numbers of CD4/CD8 T memory and nave cells.