Solid Organ Transplantation in HIV: Multi-Site Study

摘要 本研究的主要目的是评估实体器官移植在患有以下疾病患者中的安全性和有效性： 通过对接受肾脏或肾脏移植的HIV阳性（+）患者进行前瞻性、多中心队列研究， 肝移植我们的长期目标是：（1）为患者和临床医生提供有关 移植的HIV特异性风险，（2）为临床医生提供必要的信息，以管理 免疫抑制和抗逆转录病毒（ARV）药物一起，（3）了解基本的 科学机制，解释病人的结果，使临床管理可以调整，以最大限度地提高这些 结果。艾滋病毒感染者有患终末期器官疾病的重大风险。出现之前 在高活性抗逆转录病毒疗法（HAART）的情况下，这些患者通常不被视为移植候选人 因为预后不佳然而，随着HAART的使用，HIV阳性患者经历了显著的 降低发病率和死亡率。因此，越来越多的艾滋病毒阳性患者患有终末期肾病， 肝脏疾病是移植的潜在候选者。 尽管越来越多的转诊，患者和临床医生缺乏必要的数据来确定安全性和有效性， 移植和免疫抑制。由于缺乏确凿的数据， 许多移植中心和第三方支付者的护理，导致患者和 他们的医疗保健提供者。因此，本提案的主要临床重点是设计多中心 这项研究是有把握的，以测试假设，艾滋病毒+肝脏和肾脏移植受者将有病人， 移植物存活率与目前认为可接受的无HIV感染的其他患者组相当 移植候选人除了提供足够把握度研究所需的数量外，多中心研究还提供了 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， 区域准入，以避免与有限的远程站点准入相关的后勤困难。平等 重要的是，研究计划建立了一个前瞻性的队列，提供了一个理想的机会，探索 HIV+移植受者疾病进展的潜在机制及其医学治疗中的关键问题 管理多中心方法将利用病毒学领域的专家， 免疫学这些研究人员将探讨免疫抑制（IS）对HIV进展的影响， 已知在移植受者和HIV感染者中都很重要的病毒共病原体。 HIV和病毒共病原体的进展将与宿主对HIV的免疫应答的变化相关， 病毒共病原体和同种异体移植物。这些数据将为了解 可能导致移植物和患者生存率变化的因素。该队列还将提供 描述IS和肝代谢ARV之间药代动力学相互作用的基础， 将大大有利于医疗保健工作者管理艾滋病毒+患者移植后， 这两类药物的适当水平对于成功至关重要。

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.