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.

艾滋病毒感染（HIV+）个体的肾脏移植的需求日益增长，因为 肾脏疾病增加。艾滋病毒中的艾滋病毒+个体的移植结果来自艾滋病毒未感染的肾脏 （HIV-）捐助者很棒。但是，有一个严重的器官短缺，等待时间很长， 尤其是艾滋病毒+个体的候补名单死亡率更高。 来自HIV+已故捐助者（HIVD+）的器官是HIV+移植候选者的独特资源。经过 扩大供体池，使用HIVD+的器官可能会产生重大的公共卫生影响，并且 减少等待名单上每个人的等待时间。这促使国会希望（HIV器官政策 现在允许在研究方案下为HIV+受体（R+）的HIVD+移植物的权益ACT。 HIVD+移植物的潜在风险包括与供体对艾滋病毒超级感染有关的并发症 （HIV-SI）和移植后与HIV相关的肾脏疾病的发展。初步经验 但是，南非的HIVD+移植物令人鼓舞，但是，这种经验不能推广到美国 由于人口差异（种族，年龄，性别，医疗保健获取）和疾病差异（潜在的肾脏） 疾病，HIV患病率，亚型，机会性感染，抗逆转录病毒疗法的抗药性和抗药性）。 为了确定HIVD+肾脏移植在美国是否安全有效，我们提出了希望的希望： HIV+已故供体肾脏移植物的前瞻性多中心临床试验，用于HIV+受体。我们 将比较从HIV+与HIV-供体接收肾脏的HIV+接受者之间的移植结果 在16个移植中心的3年中，每组中有80个。目标1是将时间差异比较 与HIV相关的并发症和目标2比较与HIV相关肾脏疾病的发生率。在AIM 3中，我们将 表征血液中的HIV-SI及其与临床结果的关联，在AIM 4中，我们将表征 接受艾滋病毒治疗感兴趣的免疫抑制剂的参与者，艾滋病毒水库随着时间的流逝而变化。 最后，从这个独特的队列中建立丰富的组织和血液生物措施将提供 与HIV持久性和发病机理有关的未来机械研究的前所未有的机会。 在过去一年的NIAID（R34AI23023）的支持下，我们计划并设计了试验， 组建一支由移植手术，艾滋病毒/传染病，肾脏病，流行病学的专家组成的团队 生物统计学，病理学和病毒学。我们已经与UNOS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，我们正在协调多中心临床 试点研究，并进行了第一届HIVD+肾脏和肝移植。 拟议的临床试验将确定使用HIVD+是否安全有效。如果实施， 这种做法可以在过去十年中提供器官捐赠池的最大扩展，从而有可能节省 艾滋病毒+和艾滋病毒阴性个体的成千上万。