The candidate completed her M.D. and M.P.H. at the University of Michigan. During her residency in Internal Medicine she pursued her growing interest in clinical research and was awarded a Minority AIDS Training Grant from the AIDS Clinical Trials Group. She trained in Infectious Diseases, emphasizing HIV/AIDS; her research focused on HIV immunology. The primary objectives of this career development award will be to receive updated training in clinical research design, biostatistics, and research ethics, and to increase her knowledge of the basic and clinical science of immunology. The candidate's long-term goal is to become an independent clinical researcher and to focus her clinical research efforts on HIV immunology and the integration of immunology laboratory techniques and observations into therapeutic strategies. This research proposal explores a strategy for improving immune restoration in HIV- infected individuals who have achieved incomplete immune reconstitution following treatment with HAART. HIV disease is associated with progressive loss of CD4+ T-lymphocytes of both na?ve and memory phenotype and consequently a loss of immune response to specific antigens and HIV itself. Following treatment with HAART, improvements in CD4+ lymphocytes are observed in most patients. Importantly, in many patients cellular restoration following HAART is incomplete. Naive and memory CD4 cell counts improve but do not return to the levels seen in HIV seronegative persons. Furthermore, although improvements in immune response to antigens have been described, restoration of immune competence is incomplete and HIV specific immune responses remain weak or absent in most subjects despite long-term therapy. There is evidence to suggest the incompleteness of immune restoration following HAART results at least in part from a limitation in the ability of the thymus to produce new cells. Studies have shown that growth hormone therapy is associated with increases in thymic mass, improvement in thymic function, and lymphocyte proliferation in animals. In addition, there is evidence that administration of growth hormone leads to improvements in HIV specific responses in HIV infected adults following vaccination with HIV antigens. The candidate proposes that administration of growth hormone to HIV infected adults with incomplete immune restoration following HAART will lead to improvements in cellular immune restoration and cell mediated response to antigens.
