ANTIRETROVIRAL THERAPY AND LONG-TERM CLINICAL OUTCOMES

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DESCRIPTION (adapted from the application s abstract): Recent advances in antiretroviral therapy have dramatically changed the treatment and clinical outcomes for persons with HIV infection. The goal of therapy has expanded from delaying HIV disease progression and death to suppressing viral replication below the level of quantitation for as long as possible to permit immunologic improvement and clinical stabilization. However, now there is a growing proportion of patients who cannot maintain viral suppression often despite changing and more complex therapeutic regimens. The candidate hypothesis s that in the clinic setting, in contrast to the clinical trials setting, a steadily increasing proportion of patients will not have sustained suppression of viral replication over the long-term. Better definition of the generic relationship between longitudinal urologic and immunologic measures and long-term clinical outcomes across the enormous number of antiretroviral combinations available, will become increasingly essential to clinicians. In addition, there is a need to assess potential survival benefits of early and prolonged potent antiretroviral treatment in relation to the long-term effects of treatment-related events, such as neuropathy and metabolic complications (e.g. hyperlipidemia, hyperglycemia), on health-related quality-of-life and quality-adjusted survival. To complement and extend information available from clinical efficacy trials, the investigator proposes an epidemiological investigation of predictors of AIDS-free survival and quality-adjusted survival among HIV infected individuals receiving potent combination antiretroviral therapies. For this purpose, she has developed a computerized medical information system at the University of Washington that captures real-time clinical practice information for an HIV clinic population in the Northwest. Collection of comprehensive longitudinal information about HIV infected patients in this clinic setting, may enable the candidate to develop sets of measures of virologic, immunologic, and clinical responses to potent antiretroviral treatment that best predict long-term clinical outcomes. The mentoring and additional training provided by the Mentored Patient-Oriented Research Award will provide the candidate with an opportunity to devote significant efforts to research questions using the clinical information system and to develop the skills necessary to pursue a research career that blends epidemiological approaches and health services research.