Solid Organ Transplantation in HIV: Multi-Site Study

描述(由申请人提供)： 这项研究的主要目的是通过对接受肾或肝移植的HIV阳性(+)患者进行前瞻性的多中心队列研究，评估实体器官移植在HIV疾病患者中的安全性和有效性。我们的长期目标是：(1)向患者和临床医生提供有关移植的艾滋病毒特有风险的信息，(2)为临床医生提供必要的信息，以共同管理免疫抑制和抗逆转录病毒(ARV)药物，以及(3)了解解释患者结果的潜在基本科学机制，以便可以调整临床管理，使结果最大化。感染艾滋病毒的患者患终末期器官疾病的风险很大。在高效抗逆转录病毒疗法(HAART)出现之前，这些患者往往因为预后不佳而不被认为是移植对象。然而，随着HAART的使用，HIV阳性患者的发病率和死亡率都有了显著的改善。因此，越来越多的HIV+终末期肾脏和肝脏疾病患者是潜在的移植对象。尽管转诊增加，但患者和临床医生缺乏必要的数据来确定移植和免疫抑制在这一群体中的安全性和有效性。由于缺乏确凿的数据，许多移植中心和第三方付款人继续拒绝治疗，导致患者和他们的医疗保健提供者感到沮丧和困惑。因此，这项建议的主要临床重点是设计一项多中心研究，旨在检验这样一种假设，即HIV+肝和肾移植接受者的患者和移植物存活率将与目前被认为是可接受的移植候选者的其他未感染HIV的患者组相同。除了提供足够强大的研究所需的数字外，这项多中心研究还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，为区域通道提供便利，以避免与有限的远程站点访问相关的后勤困难。同样重要的是，该研究计划建立了一个前瞻性队列，为探索HIV+移植接受者疾病进展的潜在机制和他们医疗管理中的关键问题提供了一个理想的机会。多中心方法将利用获得病毒学和免疫学领域专家的机会。这些研究人员将探索免疫抑制(IS)对HIV和已知对移植接受者和HIV感染者都很重要的病毒共病原体进展的影响。HIV和病毒共病原体的进展将与宿主对HIV、病毒共病原体和同种异体移植物的免疫反应的变化相关。这些数据将为理解可能导致移植物和患者存活率变化的因素提供重要的贡献。这一队列还将为描述IS和肝脏代谢的ARV之间的药代动力学相互作用提供基础，这些数据将极大地帮助管理移植后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。

DESCRIPTION (provided by applicant): 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 o 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 the 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.