Solid Organ Transplantation in HIV: Multi-Site Study

描述（由申请人提供）： 本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、多中心队列研究，评价实体器官移植在HIV疾病患者中的安全性和有效性。我们的长期目标是：（1）为患者和临床医生提供有关移植的HIV特异性风险的信息，（2）为临床医生提供同时管理免疫抑制和抗逆转录病毒（ARV）药物所需的信息，（3）了解解释患者结局的潜在基础科学机制，以便调整临床管理以最大限度地提高结局。艾滋病毒感染者有患终末期器官疾病的重大风险。在高效抗逆转录病毒疗法（HAART）出现之前，这些患者通常不被认为是基于预后不良的移植候选人。然而，随着高效抗逆转录病毒疗法的使用，艾滋病毒阳性患者的发病率和死亡率有了显著改善。因此，越来越多的HIV阳性终末期肾病和肝病患者是移植的潜在候选人。尽管越来越多的转介，患者和临床医生缺乏必要的数据，以确定在这组移植和免疫抑制的安全性和有效性。缺乏结论性数据导致许多移植中心和第三方支付者继续拒绝护理，导致患者及其医疗保健提供者的沮丧和困惑。因此，本提案的主要临床重点是设计一项多中心研究，该研究旨在检验以下假设：HIV+肝和肾移植受者的患者和移植物存活率与目前认为可接受的移植候选人中未感染HIV的其他患者组相当。除了提供足够把握度的研究所需的数量外，多中心研究还为面临终末期器官疾病的HIV+患者提供了16个移植中心的访问，促进了区域访问，以避免与远程站点访问受限相关的后勤困难。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+移植受者疾病进展的机制及其医疗管理中的关键问题提供了理想的机会。多中心方法将利用病毒学和免疫学领域的专家。这些研究人员将探索免疫抑制（IS）对HIV和病毒共病原体进展的影响，这些共病原体在移植受者和HIV感染者中都很重要。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应答的变化相关。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做出重要贡献。该队列还将为描述IS和肝代谢ARV之间的药代动力学相互作用提供基础，这些数据将极大地受益于移植后管理HIV+患者的医护人员，因为维持这两类药物的适当水平对于成功至关重要。

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.