Risk assessment of HIV infected to HIV infected transplantation in SA

南澳艾滋病毒感染者移植的风险评估

• 批准号: 8994273
• 负责人: Elmi Muller
• 金额: $ 17.5万
• 依托单位: UNIVERSITY OF CAPE TOWN
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-15 至 2019-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8994273
• 关键词: AIDS-Associated Nephropathy; Africa; Africa South of the Sahara; Anti-Retroviral Agents; Biological; Biopsy; Caring; Cells; Chronic; Chronic Kidney Failure; Clinical; Clinical Data; Congresses; Country; Cox Proportional Hazards Models; Data; Dialysis procedure; Disease; Drug resistance; End stage renal failure; Epithelium; Frequencies; Future; HIV; HIV Seropositivity; Health; Incidence; Individual; Infiltration; Kidney; Kidney Transplantation; Lasers; Lead; Left; Leukocytes; Life; Microdissection; Minor; Nature; Organ; Organ Transplantation; Patients; Pilot Projects; Policies; Population; Probability; Recurrence; Reporting; Research; Resistance; Risk Assessment; Risk Factors; Role; Safety; Sclerosis; Source; South Africa; South African; Techniques; Testing; Tissues; Transplant Recipients; Transplantation; Tubular formation; Viral; Viral reservoir; Virus; Virus Replication; Waiting Lists; base; clinical care; clinical practice; digital; experience; glomerulosclerosis; interstitial cell; next generation sequencing; novel; podocyte; success; superinfection; therapy resistant; viral resistance

 DESCRIPTION (provided by applicant): The success of anti-retroviral therapy (ART) has led to an increased number of HIV-infected individuals experiencing complicated chronic non-infectious diseases including HIV-Associated Nephropathy (HIVAN) and subsequent End Stage Renal Disease (ESRD). Although renal transplantation is the most favorable and often only treatment option, the probability of dying on the waiting list for a healthy organ is higher than te probability of receiving one. The use of HIV-infected Deceased Donors (HIVDD) as a novel source of kidneys could alleviate the organ shortage. South Africa is the only country globally doing HIVDD kidney transplantation to HIV infected recipients, and the US is considering this option. Hence there is a need to evaluate the efficacy and safety of HIV- infected-to-HIV-infected organ transplantation. In this application we will study the only population of HIV-positive to positive transplant patients in the world in order to identify virological factors that underlie the re-emergence of HIVAN after transplantation. To this end we will first determine the incidence, extent, and nature of donor-to- recipient HIV-superinfection using drug resistance testing, digital droplet PCR, and two distinct next- generation sequencing techniques. Secondly we will quantify recipient's virus infiltration into the graft kidney and investigate virus compartmentalization in the kidney epithelium using laser directed microdissection. And finally we will investigate whether these and other factors are associated with re- emergence of HIVAN in HIV-infected-to-HIV-infected recipients. The results of this study will have a direct and immediate influence on transplant clinical practice in South Africa and on clinical decisions and policy in the US as was called for in the US landmark HIV Organ Policy Equity (HOPE) Act in November 2013. Additionally, our study provides an opportunity to answer multiple fundamental biological questions surrounding HIV-SI, viral infiltration into tissues, the role of minor ART resistance for future care, and factors that influence establishment of tissue specific viral reservoirs, which would be informative for HIV cure research.

 描述（由申请人提供）：抗逆转录病毒治疗（ART）的成功导致越来越多的HIV感染者出现复杂的慢性非感染性疾病，包括HIV相关肾病（HIVAN）和随后的终末期肾病（ESRD）。虽然肾移植是最有利的，往往是唯一的治疗选择，死亡的概率在等待一个健康的器官的概率高于接受一个。使用感染艾滋病毒的已故捐献者（HIV DD）作为肾脏的新来源可以缓解器官短缺问题。南非是全球唯一一个对艾滋病毒感染者进行肾移植的国家，美国正在考虑这一选择。因此，需要评估HIV感染者至HIV感染者器官移植的有效性和安全性。在本申请中，我们将研究世界上唯一的HIV阳性至阳性移植患者人群，以确定 是移植后艾滋病毒再次出现的原因。为此，我们将首先使用耐药性检测、数字液滴PCR和两种不同的下一代测序技术来确定供体-受体HIV重叠感染的发生率、程度和性质。其次，我们将量化受体的病毒浸润到移植肾，并研究病毒在肾上皮细胞利用激光定向显微切割区室化。最后，我们将调查这些因素和其他因素是否与HIV感染者到HIV感染者的HIV AN重新出现有关。这项研究的结果将对南非的移植临床实践和美国的临床决策和政策产生直接和直接的影响，这是2013年11月美国具有里程碑意义的HIV器官政策公平（HOPE）法案所要求的。此外，我们的研究提供了一个机会来回答围绕HIV-SI的多个基本生物学问题，病毒浸润到组织中，未来护理中轻微ART抗性的作用，以及影响组织特异性病毒库建立的因素，这将为HIV治疗研究提供信息。