Thrombocytopenia & HIV/HCV: Risk Factors & Treatment

描述（由申请方提供）：丙型肝炎病毒（HCV）相关肝病是HIV感染患者发病率/死亡率不断增加的原因。用聚乙二醇干扰素和利巴韦林治疗HCV在不到一半的HIV感染者中获得持续的病毒学应答。由于血小板减少症，聚乙二醇干扰素的剂量减少和停药通常是必需的，因此，预先存在的血小板减少症或HCV治疗期间血小板减少症的发展阻碍了有效治疗HCV的能力。拟定研究的目的是描述HIV感染患者血小板减少症的流行病学特征和风险因素，并研究HCV治疗背景下血小板减少症潜在治疗的安全性、疗效和作用机制。为了明确血小板减少症的患病率和危险因素，建议对HIV感染门诊患者伴和不伴血小板减少症进行病例对照研究。为了测试两种机制不同的血小板减少症治疗策略的安全性和有效性，提出了两项前瞻性初步临床试验：（1）利用抗D免疫球蛋白减少Fc受体阻断剂对外周血小板的破坏（2）利用血小板生成剂增加巨核细胞生成。这些研究将首次探讨HIV/HCV合并感染时血小板减少症的治疗策略。候选人将与一个多学科的导师和合作者小组密切合作，他们在以患者为导向的研究中具有与HIV感染，HCV感染和免疫性血小板减少性紫癜相关的专业知识。在导师Glesby和Gulick博士的监督下，她将通过威尔医学院的临床研究硕士课程的教学培训来补充她的研究经验。本提案中概述的研究计划、环境、教学培训和指导将为候选人作为独立研究者的职业生涯做好准备，其长期研究目标是设计和实施临床研究，以评估改善HIV感染患者HCV感染治疗的安全性、有效性和耐受性的策略。

DESCRIPTION (provided by applicant): 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.