Department of Medicine, Division of Infectious Diseases and.
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
J Clin Invest. 2024 Sep 10;134(20):e181560. doi: 10.1172/JCI181560.
BACKGROUNDThe HIV Organ Policy Equity (HOPE) Act allows individuals living with HIV to accept organs from donors with HIV. This practice widens the pool of available organs, but also presents important virological issues, including the potential for HIV superinfection of the recipient, viral persistence in the kidney, and loss of virological control.METHODSWe addressed these issues by performing in-depth longitudinal viral sequence analyses on urine, blood, and urine-derived renal epithelial cells from 12 recipients of HIV+ kidney allografts.RESULTSWe amplified donor-derived HIV-1 env sequences in 5 out of 12 recipients after transplant. These donor-derived env sequences were amplified from recipient urine, urine-derived renal epithelial cells, and plasma between 12 and 96 hours after transplant and remained detectable up to 16 days after transplant. Env sequences were also detected in kidney biopsies taken from the allografts before implantation in 6 out of the 12 transplant cases, indicating the presence of donor virus within the organ. One recipient had a viremic episode 3.5 years after transplantation as a result of antiretroviral therapy (ART) interruption. Only recipient strain viral sequences were detected in blood, suggesting that the donor virus, if still present, was not reactivated during the temporary ART withdrawal.CONCLUSIONSThis study demonstrates that the HIV env sequences in a donor kidney can be amplified from biopsies taken from the allograft before implantation and can be detected transiently in blood and urine samples collected from the organ recipients after transplantation.FUNDINGNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant number R01DK131497.
《艾滋病毒器官政策公平(HOPE)法案》允许艾滋病毒感染者接受携带艾滋病毒的捐赠者的器官。这种做法扩大了可用器官的范围,但也带来了重要的病毒学问题,包括受者感染艾滋病毒的潜在风险、肾脏中病毒的持续存在以及病毒学控制的丧失。
我们通过对 12 名接受 HIV+肾移植的受者的尿液、血液和尿液衍生的肾上皮细胞进行深入的纵向病毒序列分析来解决这些问题。
我们在移植后 5 名受者的 12 名受者中扩增了供者衍生的 HIV-1 env 序列。这些供体衍生的 env 序列是在移植后 12 至 96 小时内从受者尿液、尿液衍生的肾上皮细胞和血浆中扩增出来的,在移植后 16 天内仍可检测到。在 12 例移植病例中,有 6 例在移植前的肾活检中也检测到了供体病毒的 env 序列,这表明器官内存在供体病毒。一名受者在移植后 3.5 年因抗逆转录病毒治疗(ART)中断而出现病毒血症。只有受者株病毒序列在血液中被检测到,这表明供体病毒,如果仍然存在的话,在暂时停止 ART 期间并未被重新激活。
本研究表明,供体肾脏中的 HIV env 序列可以从移植前取自移植物的活检中扩增出来,并可以在移植后从器官受者采集的血液和尿液样本中短暂检测到。
美国国立糖尿病、消化和肾脏疾病研究所(NIDDK)资助号 R01DK131497。