Thrombocytopenia & HIV/HCV: Risk Factors & Treatment

描述(由申请人提供)：丙型肝炎病毒(丙型肝炎病毒)相关的肝病是艾滋病毒感染患者发病/死亡的一个日益增加的原因。用聚乙二醇干扰素和利巴韦林治疗丙型肝炎病毒，在不到一半的艾滋病毒感染者中实现了持续的病毒学应答。由于血小板减少，通常需要减少剂量和停用聚乙二醇干扰素，因此在丙型肝炎治疗过程中预先存在的血小板减少或出现的血小板减少阻碍了有效治疗丙型肝炎病毒的能力。这些研究的目的是描述HIV感染患者中血小板减少症的流行病学特征和危险因素，并探讨在丙型肝炎病毒治疗的背景下，潜在的治疗血小板减少症的安全性、有效性和作用机制。为了确定血小板减少症的患病率和危险因素，建议对有和不有血小板减少症的HIV感染门诊患者进行病例对照研究。为了检验两种不同治疗策略治疗血小板减少症的安全性和有效性，我们提出了两项前瞻性的初步临床试验：(1)利用抗-D免疫球蛋白减少Fc受体阻滞剂对外周血血小板的破坏；(2)利用造血剂增加巨核细胞的生成。这些研究将是第一次研究艾滋病毒/丙型肝炎病毒感染背景下的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，这些导师和合作者在与艾滋病毒感染、丙型肝炎病毒感染和免疫性血小板减少性紫癜相关的以患者为导向的研究方面具有专业知识。在格拉斯比博士和古力克博士的指导下，她将通过威尔医学院的临床调查硕士项目，用教学培训补充她的研究经验。这项建议中概述的研究计划、环境、教学培训和指导将为候选人作为一名独立调查员的职业生涯做好准备，她的长期研究目标是设计和实施临床研究，以评估改善艾滋病毒感染患者丙型肝炎病毒感染治疗的安全性、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.