Thrombocytopenia & HIV/HCV: Risk Factors & Treatment

血小板减少症

• 批准号: 6947377
• 负责人: KRISTEN M MARKS
• 金额: $ 13.15万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6947377
• 关键词: AIDS therapy; HIV infections; antiantibody; antibody receptor; antiviral agents; clinical research; disease /disorder proneness /risk; hepatitis C; hepatitis C virus; human immunodeficiency virus; human subject; human therapy evaluation; immunoglobulin D; patient oriented research; polyethylene glycols; secondary infection; thrombocytopenia; thrombopoietic factor

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.

描述（由申请人提供）：丙型肝炎病毒 (HCV) 相关肝病是 HIV 感染者发病/死亡的一个日益增加的原因。使用聚乙二醇干扰素和利巴韦林治疗 HCV 可使不到一半的 HIV 感染者获得持续的病毒学应答。由于血小板减少症，通常需要减少聚乙二醇干扰素的剂量并停用聚乙二醇干扰素，因此先前存在的血小板减少症或在HCV治疗期间出现血小板减少症会妨碍有效治疗HCV的能力。拟议研究的目的是描述 HIV 感染患者血小板减少症的流行病学和危险因素，并研究 HCV 治疗中血小板减少症潜在治疗方法的安全性、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，建议对患有或不患有血小板减少症的艾滋病毒感染门诊患者进行病例对照研究。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、试点临床试验：（1）利用抗 D 免疫球蛋白通过 Fc 受体阻断来减少外周血小板破坏（2）利用血小板生成剂来增加巨核细胞生成。这些研究将首次探讨 HIV/HCV 合并感染情况下血小板减少症的治疗策略。候选人将与一个由导师和合作者组成的多学科小组密切合作，他们在以患者为中心的艾滋病毒感染、丙型肝炎病毒感染和免疫性血小板减少性紫癜相关研究方面具有专业知识。在导师的监督下，博士。在 Glesby 和 Gulick 的帮助下，她将通过威尔医学院的临床研究硕士课程通过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，以评估提高治疗安全性、有效性和耐受性的策略HIV 感染者中 HCV 感染的情况。