HIV阳性器官移植的主要风险之一是由于供体来源的HIV超感染而失去病毒学控制,当HIV阳性个体感染了一种新的独特的HIV毒株时,就会发生这种情况。在这项研究中,作为更大规模的艾滋病毒机构政策公平试点研究的一部分,在美国,对HIV阳性的肾脏和肝移植受者的HIV阳性进行了检查,以寻找持续的供体来源的HIV重复感染的证据。
在这个多中心,prospective,观察性研究,在美国的三家医院中,对HIV阳性的肾脏和肝脏移植受者进行了跟踪。在ART上HIV感染控制良好的候选人,无活动性机会性感染,和最低CD4T细胞计数(根据联邦指南,肝脏>100个细胞/μL,肾脏>200个细胞/μL)符合接受无活动性感染或肿瘤的已死亡HIV阳性供体的肾脏或肝脏的条件.在移植时从供体-受体对收集外周血单核细胞,以及移植后长达3年的几个时间点的接受者。评估供体样本的HIVRNA病毒载量,CD4细胞计数,和抗逆转录病毒药物抗性突变。供体和受体HIV前病毒DNA,使用针对逆转录酶和gp41基因的定点下一代测序测定法对病毒血症时间点的病毒RNA进行测序。使用相邻连接的系统发育树和直接序列比较来检测HIV超感染的存在。这项研究在ClinicalTrials.gov注册,NCT02602262。
从3月开始随访了14名HIV阳性肾脏和8名肝移植受者,2016年7月,2019.17个接受者具有足够的病毒序列,可以进行HIV重复感染评估。8个供体被抑制(病毒载量<400拷贝/mL),并且没有检测到多类耐药突变。接受检查的受检者都没有艾滋病毒双重感染的证据。由于不坚持ART,一名受体在移植后3年出现病毒血症(病毒载量为2080000拷贝/mL)。在病毒血症发作期间仅检测到受体病毒序列,表明供体病毒,如果存在,尽管暂时撤回了ART,但并未重新激活。
这些发现表明,在仔细监测ART抑制HIV阳性器官受者中,由于供体来源的HIV重复感染而导致的HIV抑制丧失可能不是一个重要的临床问题。
美国国家过敏和传染病研究所和国家癌症研究所。
One of the primary risks of HIV-positive to HIV-positive organ transplantation is loss of virological control because of donor-derived HIV superinfection, which occurs when an HIV-positive individual becomes infected with a new distinct HIV strain. In this
study, as part of the larger HIV Organ Policy Equity pilot
study, HIV-positive to HIV-positive kidney and liver transplant recipients in the USA were examined for evidence of sustained donor-derived HIV superinfection.
In this multicentre, prospective, observational
study, HIV-positive to HIV-positive kidney and liver transplant recipients were followed in three hospitals in the USA. Candidates with well controlled HIV infection on ART, no active opportunistic infections, and minimum CD4 T-cell counts (>100 cells per μL for liver and >200 cells per μL for kidney per federal guidelines) were eligible to receive a kidney or liver from deceased HIV-positive donors without active infections or neoplasm. Peripheral blood mononuclear cells were collected from donor-recipient pairs at the time of transplantation, and from recipients at several timepoints up to 3 years after transplantation. Donor samples were assessed for HIV RNA viral load, CD4 cell count, and antiretroviral drug-resistant mutations. Donor and recipient HIV proviral DNA, and viral RNA from the viraemic timepoint were sequenced using a site-directed next-generation sequencing assay for the reverse transcriptase and gp41 genes. Neighbour-joining phylogenetic trees and direct sequence comparison were used to detect the presence of HIV superinfection. This
study is registered with ClinicalTrials.gov, NCT02602262.
14 HIV-positive to HIV-positive kidney and eight liver transplant recipients were followed from March, 2016, to July, 2019. 17 recipients had adequate viral sequences allowing for HIV superinfection assessment. Eight donors were suppressed (viral load <400 copies per mL), and none had multiclass drug-resistant mutations detected. None of the recipients examined had evidence of HIV superinfection. One recipient had a viraemic episode (viral load of 2 080 000 copies per mL) 3 years after transplantation as a result of non-adherence to ART. Only recipient viral sequences were detected during the viraemic episode, suggesting that the donor virus, if present, was not reactivated despite temporary withdrawal of ART.
These findings suggest that loss of HIV suppression due to donor-derived HIV superinfection might not be a significant clinical concern in carefully monitored ART suppressed HIV-positive organ recipients.
US National Institute of Allergy and Infectious Diseases and National Cancer Institute.