Solid Organ Transplantation in HIV: Multi-Site Study

HIV 实体器官移植：多中心研究

• 批准号: 7850382
• 负责人: PETER G STOCK
• 金额: $ 72.96万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7850382
• 关键词: Acceleration; Address; Allografting; Anti-Retroviral Agents; Area; Basic Science; CD4 Positive T Lymphocytes; Caring; Cell Count; Clinical; Clinical Management; Clinical Practice Guideline; Cohort Studies; Complex; Confusion; Cyclosporine; Cyclosporins; Cytochrome P450; Cytomegalovirus; Data; Development; Disease; Disease Progression; Distant; Dose; Drug Kinetics; Evaluation; Frustration; Funding; Future; Goals; Graft Survival; Guidelines; HIV; HIV Infections; HIV Seropositivity; HIV-1; Health Personnel; Hepatitis B; Herpesviridae; Highly Active Antiretroviral Therapy; Human; Human Herpesvirus 6; Human Herpesvirus 8; Human Papillomavirus; Immune; Immune response; Immune system; Immunologics; Immunology; Immunosuppression; Immunosuppressive Agents; Impaired Renal Function; Infection; Intervention; Kidney; Kidney Diseases; Kidney Transplantation; Liver; Liver diseases; Logistics; Mediating; Medical; Modification; Morbidity - disease rate; Multicenter Studies; Organ; Organ Transplantation; Organism; Outcome; Pathogenesis; Pathway interactions; Patients; Pharmaceutical Preparations; Phenotype; Prevalence; Prospective Studies; Protease Inhibitor; Protocols documentation; RNA; Recurrence; Relative (related person); Reporting; Research; Research Personnel; Risk; Safety; Sampling; Satellite Viruses; Sirolimus; Site; Solid; Specimen; Staging; Survival Rate; System; T-Lymphocyte; Tacrolimus; Testing; Third-Party Payer; Time; Transplant Recipients; Transplantation; Variant; Viral; Viral hepatitis; abstracting; base; clinically significant; cohort; design; experience; graft failure; liver transplantation; mortality; multidisciplinary; neoplastic; non-nucleoside reverse transcriptase inhibitors; outcome forecast; pathogen; post-transplant disease; prospective; response; success; virology

ABSTRACT The primary aim of this study is to evaluate the safety and efficacy of solid organ transplantation in people with HIV disease by conducting a prospective, multi-center cohort of HIV-positive (+) patients who undergo kidney or liver transplantation. Our long-range goals are: (1) to provide patients and clinicians with information regarding the HIV-specific risks of transplantation, (2) to provide clinicians with information necessary to manage immunosuppressive and antiretroviral (ARV) medications together, and (3) to understand underlying basic science mechanisms that explain patient outcomes so that clinical management can be adjusted to maximize these outcomes. Patients with HIV infection are at significant risk for end stage organ disease. Prior to the advent of highly active antiretroviral therapy (HAART), such patients were often not considered as transplant candidates based on poor prognosis. However, with the use of HAART, HIV positive patients have experienced significant improvements in morbidity and mortality. Thus, increasing numbers of HIV+ patients with end stage kidney and liver disease are potential candidates for transplantation. Despite increasing referrals, patients and clinicians lack the necessary data to determine the safety and efficacy of transplantation and immunosuppression in this group. This lack of conclusive data has led to continued denial of care by many transplant centers and third party payers, resulting in frustration and confusion for both patients and their health care providers. Therefore, the primary clinical focus of this proposal is the design of a multi-center study that is powered to test the hypothesis that HIV+ liver and kidney transplant recipients will have patient and graft survival rates equivalent to other patient groups without HIV infection currently considered acceptable transplant candidates. In addition to providing the numbers required for a sufficiently powered study, the multicenter study provides access to 16 transplant centers for HIV+ patients facing end stage organ disease, facilitating regional access to avoid the logistic difficulties associated with limited access to distant sites. Of equal importance, the research plan establishes a prospective cohort that provides an ideal opportunity to explore mechanisms underlying disease progression in HIV+ transplant recipients and key issues in their medical management. The multi-center approach will capitalize on access to experts in the fields of virology and immunology. These investigators will explore the effects of immunosuppression (IS) on progression of HIV and viral co-pathogens known to be important in both transplant recipients and people with HIV infection. Progression of HIV and viral co-pathogens will be correlated with changes in the host immune response to HIV, viral co-pathogens, and allografts. These data will provide an essential contribution to an understanding of the factors that may be responsible for variations in graft and patient survival rates. This cohort will also provide the basis for describing the pharmacokinetic interactions between IS and the hepatically-metabolized ARVs, data that will greatly benefit health care workers managing HIV+ patients following transplantation, as maintaining appropriate levels of both of these classes of drugs will be essential for success.

摘要 本研究的主要目的是评价实体器官移植治疗慢性阻塞性肺疾病的安全性和有效性。 通过对HIV阳性(+)患者进行前瞻性、多中心队列研究，这些患者接受肾脏或 肝脏移植。我们的长期目标是：(1)为患者和临床医生提供以下信息 移植的艾滋病毒特有风险，(2)为临床医生提供管理所需的信息 免疫抑制和抗逆转录病毒(ARV)药物一起使用，以及(3)了解潜在的基础知识 解释患者结果的科学机制，以便调整临床管理以最大限度地提高这些 结果。感染艾滋病毒的患者患终末期器官疾病的风险很大。在……出现之前 高效抗逆转录病毒疗法(HAART)，这样的患者通常不被认为是移植候选 基于预后不佳。然而，随着HAART的使用，HIV阳性患者经历了显著的 发病率和死亡率的改善。因此，越来越多的HIV+终末期肾病患者和 肝脏疾病是潜在的移植对象。 尽管转诊人数不断增加，但患者和临床医生缺乏必要的数据来确定联合化疗的安全性和有效性 移植和免疫抑制在本组。由于缺乏确凿的数据，人们继续否认 许多移植中心和第三方付款人的护理，导致患者和 他们的医疗保健提供者。因此，这一方案的主要临床焦点是设计一个多中心 一项旨在检验HIV+肝肾移植受者将有患者和 目前认为可接受的移植物存活率与其他未感染艾滋病毒的患者组相当 移植候选人。除了提供足够动力的研究所需的数字外，多中心 这项研究为面临终末期器官疾病的HIV+患者提供了16个移植中心的通道，为 区域准入，以避免与进入遥远地点的有限相关的后勤困难。平等的 重要的是，研究计划建立了一个预期的队列，提供了一个理想的探索机会 HIV+移植受者疾病进展的机制及其医疗中的关键问题 管理层。多中心方法将利用接触病毒学和 免疫学。这些研究人员将探索免疫抑制(IS)对艾滋病毒和艾滋病进展的影响 已知的病毒共病原体对移植受者和艾滋病毒感染者都很重要。 艾滋病毒和病毒共病原体的进展将与宿主对艾滋病毒的免疫反应的变化相关， 病毒共病原体和同种异体移植物。这些数据将为理解 可能导致移植物和患者存活率差异的因素。这一队列还将提供 描述IS和肝脏代谢的抗逆转录病毒药物之间药代动力学相互作用的基础，数据 将极大地有利于管理移植后HIV+患者的医护人员，因为保持 这两类药物的适当水平将是成功的关键。