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: 10462020
• 负责人: Christine Marie Durand
• 金额: $ 336.64万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-31 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10462020
• 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，对HIV感染者（HIV+）进行肾移植的需求日益增加。 肾病分期增加。HIV阳性个体移植来自HIV未感染者的肾脏的结局 （艾滋病毒-）捐助者是优秀的。然而，器官严重短缺，等待时间极长， 尤其是HIV阳性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+移植候选人的独特资源。通过 扩大捐献者库，使用来自HIVD+的器官可能会对公共卫生产生重大影响， 减少等待名单上每个人的等待时间。这促使国会希望（艾滋病毒器官政策） 公平）法案，现在允许根据研究协议为艾滋病毒+接受者（R+）进行HIVD+移植。 HIVD+移植的潜在风险包括与供体-受体HIV重叠感染相关的并发症 （HIV-SI）和移植后HIV相关肾病的发展。的初步经验 南非的HIVD+移植令人鼓舞，但经验不能推广到美国 由于人群差异（种族、年龄、性别、卫生保健获得）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、获得抗逆转录病毒治疗的机会和对抗逆转录病毒治疗的耐药性）。 为了确定HIVD+肾移植在美国是否安全有效，我们提出了HOPE in Action： 一项前瞻性多中心临床试验，HIV+死亡供体肾移植给HIV+受体。我们 将比较从HIV+和HIV-供体接受肾脏的HIV+受体之间的移植结果 在16个移植中心，每组招募80人，为期3年。目标1是比较时间上的差异， HIV相关并发症与目的2比较HIV相关肾脏疾病的发病率。在目标3中，我们 描述血液中的HIV-SI及其与临床结局的关系，在目标4中，我们将描述 在接受HIV治疗的免疫抑制剂的参与者中，HIV库随时间的变化。 最后，从这个独特的队列建立一个丰富的组织和血液生物储存库将提供一个 这为今后有关艾滋病毒持久性和发病机制的机制研究提供了前所未有的机会。 在NIAID（R34 AI 23023）过去一年的支持下，我们计划并设计了试验， 组建了一个移植外科、艾滋病毒/传染病、肾脏病学、流行病学、 生物统计学、病理学和病毒学。我们与联合国海洋观测系统和OPTN合作，正在进行一项研究， 在全国范围内识别和评价HIVD+（R 01 AI 120938）。此外，我们正在协调一项多中心临床研究， 该公司已经完成了美国首例HIVD+肾脏和肝脏移植。 拟议的临床试验将确定使用HIVD+是否安全有效。如果实施， 这种做法可能会在过去十年中最大程度地扩大器官捐献者库， 数以千计的艾滋病毒阳性和阴性个体的生命。

项目成果

Detectable plasma severe acute respiratory syndrome coronavirus 2 spike antigen is associated with poor antibody response following third messenger RNA vaccination in kidney transplant recipients.

在肾移植受者中，可检测到的血浆严重急性呼吸综合征冠状病毒 2 刺突抗原与第三信使 RNA 疫苗接种后抗体反应不佳有关。

• DOI: 10.1111/tid.14281
• 发表时间: 2024
• 期刊: Transplant infectious disease : an official journal of the Transplantation Society
• 作者: Karaba,AndrewH;Swank,Zoe;Hussain,Sarah;Chahoud,Margaret;Durand,ChristineM;Segev,DorryL;Robien,MarkA;Heeger,PeterS;Larsen,ChristianP;Tobian,AaronAR;Walt,DavidR;Werbel,WilliamA
• 通讯作者: Werbel,WilliamA

Solid Organ Transplantation for HIV-Infected Individuals.

• DOI: 10.1007/s40506-018-0144-1
• 发表时间: 2018-03
• 期刊: Current treatment options in infectious diseases
• 影响因子: 2
• 作者: Shaffer AA;Durand CM
• 通讯作者: Durand CM

Donors with human immunodeficiency virus and hepatitis C virus for solid organ transplantation: what's new.

• DOI: 10.1097/qco.0000000000000840
• 发表时间: 2022-08-01
• 期刊: Current opinion in infectious diseases
• 影响因子: 3.9