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

希望在行动：艾滋病毒转艾滋病毒死者供体肾移植的临床试验

• 批准号: 10214499
• 负责人: Christine Marie Durand
• 金额: $ 141.61万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-05 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10214499
• 关键词: APOL1 gene; Acquired Immunodeficiency Syndrome; Age; Allografting; Anti-HIV Agents; Antibodies; Antiretroviral resistance; Antithymoglobulin; Biological; Biometry; Biopsy; Blood; CD4 Lymphocyte Count; Case Report Form; Cell Count; Cessation of life; Clinical; Clinical Trials; Communicable Diseases; Communities; Consent; Databases; Development; Disease; Donor person; Drug resistance; Effectiveness; Electron Microscopy; End stage renal failure; Enrollment; Ensure; Epidemiology; Event; Failure; Funding; Future; Gender; Genetic; Genetic Risk; Graft Rejection; Grant; HIV; Health Benefit; Immune; Immunofluorescence Microscopy; Immunosuppressive Agents; Incidence; Individual; Infection; Infrastructure; Kidney; Kidney Diseases; Kidney Transplantation; Knowledge; Lead; Malignant Neoplasms; Measures; Mediating; Multi-Institutional Clinical Trial; Multicenter Studies; National Institute of Allergy and Infectious Disease; Nephrology; Opportunistic Infections; Organ; Organ Donor; Organ Procurements; Outcome; Participant; Pathogenesis; Pathologic; Pathology; Patients; Pharmaceutical Preparations; Pilot Projects; Policies; Population; Prevalence; Protocols documentation; Public Health; Race; Research; Resistance; Resources; Risk; Safety Management; Savings; Severities; Sirolimus; Source; South Africa; South African; Testing; Time; Tissues; Transplant Recipients; Transplantation; Transplantation Surgery; United Network for Organ Sharing; United States National Institutes of Health; Variant; Viral; Wait Time; Waiting Lists; antiretroviral therapy; biobank; cohort; comorbidity; data management; design; detection assay; digital imaging; donor-specific antibody; experience; frailty; graft failure; health care availability; interest; liver transplantation; living kidney donor; mortality; next generation sequencing; novel; operation; post-transplant; primary endpoint; prospective; public health relevance; recruit; repository; safety and feasibility; sex; superinfection; transplant centers; trial design; viral rebound; virology; whole slide imaging

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.

随着终末期肾病的流行，艾滋病毒感染者（HIV+）对肾移植的需求日益增长。 阶段肾脏疾病增加。 HIV+ 患者的肾脏来自未感染 HIV 的患者的移植结果 （HIV-）捐赠者非常出色。然而，器官严重短缺，等待时间极长， 尤其是艾滋病病毒感染者的等待名单死亡率更高。 来自 HIV+ 已故捐献者 (HIVD+) 的器官是 HIV+ 移植候选者的独特资源。经过 扩大捐赠者库，使用 HIVD+ 的器官可能会对公共卫生产生重大影响，并且 减少候补名单上每个人的等待时间。这激发了国会希望（HIV器官政策 公平）法案现在允许根据研究方案对 HIV+ 接受者 (R+) 进行 HIVD+ 移植。 HIVD+ 移植的潜在风险包括与供体与受体 HIV 重复感染相关的并发症 （HIV-SI）和移植后 HIV 相关肾病的发展。初步经验 南非的 HIVD+ 移植令人鼓舞，但这一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获得和抵抗）。 为了确定 HIVD+ 肾移植在美国是否安全有效，我们建议 HOPE in Action： 对 HIV+ 已故捐献者肾脏移植用于 HIV+ 受体的前瞻性多中心临床试验。我们 将比较接受 HIV+ 和 HIV- 捐赠者肾脏的 HIV+ 受者之间的移植结果 3年内在16个移植中心每组招募80名患者。目标 1 是比较时间差异 HIV 相关并发症和目标 2 比较 HIV 相关肾脏疾病的发生率。在目标 3 中，我们将 描述血液中的 HIV-SI 及其与临床结果的关联，在目标 4 中，我们将描述 在接受用于治疗艾滋病毒的免疫抑制剂的参与者中，艾滋病毒储存库随着时间的推移而发生变化。 最后，从这个独特的群体中建立一个丰富的组织和血液生物储存库将提供 为未来与艾滋病毒持续性和发病机制相关的机制研究提供了前所未有的机会。 在过去一年NIAID（R34AI23023）的支持下，我们规划并设计了试验， 组建了移植手术、艾滋病毒/传染病、肾病学、流行病学、 生物统计学、病理学和病毒学。我们与 UNOS 和 OPTN 合作开展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，我们正在协调一项多中心临床 试点研究并进行了美国首例 HIVD+ 肾脏和肝脏移植。 拟议的临床试验将确定 HIVD+ 的使用是否安全有效。如果实施的话， 这种做法可以在过去十年中最大程度地扩大器官捐献者库，从而可能节省 成千上万的艾滋病毒阳性和艾滋病毒阴性者的生命。