Hepatitis C virus (HCV)-related liver disease is an increasing cause of morbidity/mortality in HIV-infected patients. HCV treatment with peginterferon and ribavirin achieves sustained virologic responses in less than half of HIV-infected individuals. Dose reductions and discontinuations of peginterferon are often required because of thrombocytopenia, thus preexisting thrombocytopenia or the development of thrombocytopenia during HCV therapy impedes the ability to effectively treat HCV. The objectives of the proposed studies are to characterize the epidemiology of and risk factors for thrombocytopenia in HIV-infected patients and to investigate the safety, efficacy and mechanism of action of potential treatments for thrombocytopenia in the setting of HCV treatment. To define the prevalence and risk factors for thrombocytopenia, a case-control study of HIV-infected outpatients with and without thrombocytopenia is proposed. To test the safety and efficacy of two mechanistically different treatment strategies for thrombocytopenia, two prospective, pilot clinical trials are proposed: (1) Utilizing anti-D immunoglobulin to decrease peripheral platelet destruction by Fc receptor blockade (2) Utilizing a thrombopoietic agent to increase megakaryopoiesis. These studies will be the first to investigate treatment strategies for thrombocytopenia in the setting of HIV/HCV coinfection. The candidate will work closely with a multidisciplinary group of mentors and collaborators with expertise in patient-oriented research related to HIV infection, HCV infection, and immune thrombocytopenic purpura. Under the supervision of mentors, Drs. Glesby and Gulick, she will supplement her research experience with didactic training through Weill Medical College's Masters Program in Clinical Investigation. The research plan, environment, didactic training, and mentoring outlined in this proposal will prepare the candidate for her career as an independent investigator with long term research goals of designing and implementing clinical studies to evaluate strategies for improving the safety, efficacy and tolerability of treatment of HCV infection in HIV-infected patients.
