HOPE in Action: HIV-to-HIV Solid Organ Transplantation in the US

 描述(申请人提供)：由于终末期肾脏疾病和终末期肝病的发病率上升，对艾滋病毒感染者(HIV+)的器官移植的需求越来越大。研究表明，在使用艾滋病毒未感染(HIV-)捐赠者的HIV+个人中移植的效果很好。然而，器官严重短缺，等待时间极长，特别是艾滋病毒携带者的等待名单死亡率更高。人们迫切需要一种针对HIV+感染者的新器官来源。HIVDD的器官对于等待移植的HIV+患者来说是一个独特的潜在资源。通过扩大捐赠者群体，使用艾滋病毒/艾滋病治疗方案还可以减少艾滋病毒感染者的等待时间，从而对公共卫生产生深远的影响。认识到这一需要，我们团队撰写了《艾滋病毒器官政策公平法案》(HOPE)，该法案在国会获得通过，最近由奥巴马总统于2013年11月21日签署，呼吁对艾滋病毒到艾滋病毒的器官移植进行研究。《希望法案》指示卫生与公众服务部秘书制定和公布与艾滋病毒/艾滋病器官移植相关的研究和安全性指导方针，并进一步授权卫生与公众服务部秘书决定在什么情况下允许艾滋病毒/艾滋病器官开放移植。在南非，Elmi Muller博士率先将来自HIVDD的器官用于HIV+肾移植候选人，并看到了极好的结果。然而，美国和S非洲之间的关键差异将影响艾滋病毒到艾滋病毒移植的安全性、器官质量和结果：器官疾病的患病率和原因、移植的可及性、等待名单死亡率、艾滋病毒流行率、每年艾滋病毒死亡人数和艾滋病毒感染种族、年龄、死因、并存、艾滋病毒病毒载量、CD4T细胞计数、获得抗逆转录病毒治疗(ART)和抗逆转录病毒疗法(ART)的耐药性。为了评估美国HIV-to-HIV移植的安全性、可行性和有效性，我们建议设计和计划一项多中心前瞻性研究：希望在行动。我们得到了全美20多个主要美国移植中心的支持，他们致力于协助我们设计和实施这项研究，该研究将探讨使用HIVDD器官进行肾脏和肝脏移植。主要结果将是患者存活和移植物存活，相比之下，1)使用艾滋病毒捐赠者进行艾滋病毒+移植的结果，2)等待下一个可用的艾滋病毒器官(生存益处)。次要结果将包括移植排斥反应的发生率、艾滋病毒-AN的复发、艾滋病毒重叠感染的发生率、艾滋病毒水平和CD4T细胞的变化、抗逆转录病毒药物耐药性和感染发生率。我们团队在美国国立卫生研究院资助的多中心研究方面有着长期的经验。我们已经与器官采购移植网络建立了关键的基础设施，我们聘请了NIH资助的艾滋病毒多站点研究的PI彼得·斯托克博士和使用艾滋病毒+捐赠者进行移植的世界专家埃尔米·穆勒博士担任顾问。这笔R34赠款将使拟议的临床试验能够及时启动，该试验将提供有关艾滋病毒到艾滋病毒移植的安全性、可行性和有效性的关键信息。

 DESCRIPTION (provided by applicant): There is a growing need for organ transplantation in HIV-infected (HIV+) individuals due to a rising prevalence of end-stage renal disease and end-stage liver disease. Studies demonstrate excellent outcomes of transplantation in HIV+ individuals using HIV-uninfected (HIV-) donors. However, there is a profound organ shortage, with extremely long waiting times, and a higher waitlist mortality for HIV+ individuals in particular. A novel source of organs specific to HIV+ individuals is desperately needed. Organs from HIVDD are a unique potential resource for HIV+ individuals on the transplant waitlist. By expanding the donor pool, the use of HIVDD could also decrease the wait time for HIV- individuals, resulting in a far-reaching public health impact. Recognition of this need led our group to write the HIV Organ Policy Equity (HOPE) Act which passed Congress and was recently signed by President Obama on November 21, 2013, calling for research on HIV-to-HIV organ transplants. The HOPE Act directs the Secretary of HHS to develop and publish guidelines for the conduct of research and safety relating to HIVDD organ transplantation, and further empowers the Secretary to determine at what point to allow open transplantation of HIVDD organs. In South Africa, Dr. Elmi Muller has pioneered the use of organs from HIVDD for HIV+ renal transplant candidates and seen excellent outcomes. However there are key differences between the US and S Africa that will impact safety, organ quality and outcomes of HIV-to-HIV transplantation: prevalence and causes of organ disease, access to transplantation, waitlist mortality, HIV prevalence, number of HIV deaths/year and HIVDD race, age, cause of death, co-morbidities, HIV viral load, CD4 T cell count, access to antiretroviral therapy (ART) and ART resistance. To evaluate the safety, feasibility and effectiveness of HIV-to-HIV transplantation in the US, we propose to design and plan a multicenter prospective study: HOPE in Action. We have the support of more than 20 major US transplant centers across the US who are committed to assisting us in the design and implementation of the study which will look at kidney and liver transplant using organs from HIVDD. The primary outcomes will be patient survival and graft survival, compared to 1) outcomes of HIV+ transplantation using HIV- donors and 2) waiting for the next available HIV- organ (survival benefit). Secondary outcomes will include incidence of graft rejection, recurrence of HIV-AN, incidence of HIV- superinfection, changes in HIV levels and CD4 T-cells, ART resistance, and incidence of infections. Our group has long-standing experience in NIH-funded multicenter studies. We have established critical infrastructure with the Organ Procurement Transplant Network and we have recruited Dr. Peter Stock, the PI of the NIH- funded HIV Multisite Study and Dr. Elmi Muller, the world's expert on transplantation using HIV+ donors to serve as consultants. This R34 grant will enable timely initiation of the proposed clinical trial, which will provide critical information on the safety, feasibility and effectiveness of HIV-to-HIV transplantation.