HOPE in Action: A clinical trial of HIV-to-HIV deceased donor kidney transplantation

随着终末期肾病的流行，艾滋病毒感染者(HIV)对肾移植的需求越来越大。 阶段性肾病增多。移植非HIV感染者肾脏的HIV患者的结局 (HIV-)捐赠者非常优秀。然而，器官严重短缺，等待时间非常长， 尤其是艾滋病毒感染者的等待死亡率更高。 来自艾滋病毒已故捐赠者的器官(HIVD)是艾滋病毒移植候选人的独特资源。通过 扩大捐赠者池，使用来自HIVD的器官可能会对公共卫生产生重大影响， 减少等待名单上的每个人的等待时间。这激发了国会的希望(艾滋病毒器官政策 公平)法案，现在允许根据研究协议对艾滋病毒接受者(R)进行HIVD移植。 HIVD移植的潜在风险包括与供受者艾滋病毒重叠感染相关的并发症 (艾滋病毒-SI)和移植后与艾滋病毒相关的肾脏疾病的发展。初步经验： 南非的HIVD移植令人鼓舞，但这种经验不能推广到美国 由于人口差异(种族、年龄、性别、医疗保健机会)和疾病差异(基础肾脏 疾病、艾滋病毒流行率、亚型、机会性感染、抗逆转录病毒治疗的可及性和抵抗力)。 为了确定HIVD肾移植在美国是否安全有效，我们建议行动中的希望： HIV感染者已故供者肾移植的前瞻性多中心临床试验。我们 将比较接受HIV肾移植的HIV接受者和HIV捐赠者之间的移植结果 在3年的时间里，在16个移植中心，每组招募80人。目标1是比较时间上的差异 目的2比较HIV相关并发症和HIV相关肾脏疾病的发病率。在《目标3》中，我们将 血液中HIV-SI的特征及其与临床结果的关系，在目标4中，我们将特征 接受对HIV治愈有兴趣的免疫抑制剂的参与者中，HIV储存库随时间的变化。 最后，从这个独特的队列中建立丰富的组织和血液生物储存库将提供 为未来有关艾滋病毒持久性和致病机理的机制研究提供了前所未有的机遇。 在过去的一年里，在NIAID(R34AI23023)的支持下，我们规划和设计了试验， 组建一支由移植外科、艾滋病毒/传染病、肾脏病、流行病学、 生物统计学、病理学和病毒学。我们已经与联合国操作系统和OPTN合作进行了一项正在进行的研究 在全国范围内识别和评估HIVD(R01AI120938)。此外，我们正在协调一个多中心的临床 进行了先导性研究，并进行了美国首例HIVD肾和肝移植。 拟议的临床试验将确定HIVD的使用是否安全有效。如果实施， 这一做法可以提供过去十年来最大规模的器官捐赠者池扩张，有可能节省 数以千计的艾滋病毒感染者和艾滋病毒阴性者的生命。

There is a growing need for kidney transplantation in HIV-infected (HIV+) individuals as the prevalence of end- stage renal disease increases. Outcomes of transplant in HIV+ individuals with kidneys from HIV-uninfected (HIV-) donors are excellent. However, there is a profound organ shortage, with extremely long waiting times, and a higher waitlist mortality for HIV+ individuals in particular. Organs from HIV+ deceased donors (HIVD+) are a unique resource for HIV+ transplant candidates. By expanding the donor pool, use of organs from HIVD+ could have a significant public health impact and decrease wait times for everyone on the waitlist. This motivated the Congressional HOPE (HIV Organ Policy Equity) Act which now allows HIVD+ transplants for HIV+ recipients (R+) under research protocols. Potential risks of HIVD+ transplants include complications related to donor-to-recipient HIV superinfection (HIV-SI) and development of HIV-associated kidney disease after transplant. Preliminary experience with HIVD+ transplants in South Africa is encouraging, however, the experience cannot be generalized to the US due to population differences (race, age, sex, health care access), and disease differences (underlying kidney disease, HIV prevalence, subtype, opportunistic infections, access and resistance to antiretroviral therapy). To determine if HIVD+ kidney transplantation is safe and effective in the US, we propose HOPE in Action: A Prospective Multicenter, Clinical Trial of HIV+ Deceased Donor Kidney Transplants for HIV+ Recipients. We will compare transplant outcomes between HIV+ recipients who receive kidneys from HIV+ versus HIV- donors enrolling 80 in each group over 3 years at 16 transplant centers. Aim 1 is to compare differences in time to HIV-related complications and Aim 2 to compare incidence of HIV-related kidney disease. In Aim 3, we will characterize HIV-SI in blood and its association with clinical outcomes and in Aim 4 we will characterize changes in HIV reservoirs over time in participants receiving immunosuppressants of interest for HIV cure. Finally, establishment of a rich biorepository of tissue and blood from this unique cohort will provide an unprecedented opportunity for future mechanistic studies related to HIV persistence and pathogenesis. With support from NIAID (R34AI23023) over the past year, we have planned and designed the trial, assembling a team of experts in Transplant Surgery, HIV/Infectious Diseases, Nephrology, Epidemiology, Biostatistics, Pathology and Virology. We have partnered with the UNOS and OPTN in an ongoing study to identify and evaluate HIVD+ nationally (R01AI120938). In addition, we are coordinating a multicenter clinical pilot study and have performed the first-in-US HIVD+ kidney and liver transplants. The proposed clinical trial will determine whether the use of HIVD+ is safe and effective. If implemented, this practice could provide the largest expansion of the organ donor pool in the last decade, potentially saving thousands of lives of HIV+ and HIV-negative individuals.