This application proposes David Simpson M.D. for a Mid-Career Investigator Award in Patient-Oriented Research in Neuro-AIDS. Its primary focus is to provide the Principal Investigator with support to continue his development as a productive clinician/scientist with sufficient protected time to pursue his clinical research and mentoring activities. As the first emphasis of this proposal, the Candidate proposes to continue and intensify a program of patient-oriented research, focused on the neurological disorders complicating HIV infection and AIDS. The objective is to build a clinical research program in Neuro-AIDS that engages the participation o researchers from a variety of clinical disciplines to address the multi-faceted aspects of HIV-associated neurological disorders. A primary focus of proposed new research is the prospective and longitudinal assessment of patient cohorts with advanced HIV disease in order to identify subclinical and unrecognized neurological disorders. Specific disorders of interest include peripheral neuropathy associated with HIV infection and neurotoxic antiretroviral agents, myopathy, myelopathy, and cognitive impairment. Outcomes of interest include risk factors for the development of these disorders, their correlation with virological and immunological measures, and the utility of assessment instruments. Cohorts available for these studies include the NIH-funded Manhattan Brain Bank Consortium, AIDS Clinical Trials Group studies, and pharmaceutical industry trials. Patients identified with neurological disorders will be referred into ongoing therapeutic clinical trials. The second emphasis of this proposal is the mentoring of Fellows and Junior Faculty committed to patient-oriented research. Trainees will be recruited from numerous disciplines including Neurology, Infectious Diseases and non-physician health care providers, including Nurse Practitioners and Physician Assistants- Visiting Scholars from abroad will be mentored. The Program will provide a structured curriculum incorporating a knowledge base in Neuro-AIDS, neurological examination skills, and training in clinical trial design, conduct, and analysis. The Neuro-AIDS Educational Program will incorporate an Internet-based and video case presentation series in order to provide distance learning for health care providers, patients and other communities. The Neuro-Adherence Program will assess the affect of neurological disease on patients' adherence to medical regimens, and the impact of education and support groups on adherence.