研究动态
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CCR5Δ32/Δ32同种异体造血干细胞移植后,HIV-1治愈的病毒学和免疫学深入描述。

In-depth virological and immunological characterization of HIV-1 cure after CCR5Δ32/Δ32 allogeneic hematopoietic stem cell transplantation.

发表日期:2023 Feb 20
作者: Björn-Erik Ole Jensen, Elena Knops, Leon Cords, Nadine Lübke, Maria Salgado, Kathleen Busman-Sahay, Jacob D Estes, Laura E P Huyveneers, Federico Perdomo-Celis, Melanie Wittner, Cristina Gálvez, Christiane Mummert, Caroline Passaes, Johanna M Eberhard, Carsten Münk, Ilona Hauber, Joachim Hauber, Eva Heger, Jozefien De Clercq, Linos Vandekerckhove, Silke Bergmann, Gábor A Dunay, Florian Klein, Dieter Häussinger, Johannes C Fischer, Kathrin Nachtkamp, Joerg Timm, Rolf Kaiser, Thomas Harrer, Tom Luedde, Monique Nijhuis, Asier Sáez-Cirión, Julian Schulze Zur Wiesch, Annemarie M J Wensing, Javier Martinez-Picado, Guido Kobbe
来源: NATURE MEDICINE

摘要:

尽管迄今为止已经发表了两位病人的科学证据表明CCR5Δ32/Δ32造血干细胞移植(HSCT)可以治愈人类免疫缺陷病毒类型1(HIV-1),但治愈的免疫和病毒学相关知识仍然有限。在这里,我们描述了一例经过谨慎监测的53岁男性患者的长期HIV-1缓解情况,经过异基因CCR5Δ32/Δ32 HSCT治疗急性髓性白血病后,他接受了超过9年的监测。尽管在外周T细胞亚群和组织样本中检测到零散的HIV-1 DNA痕迹,但重复的体外定量和体内增殖实验在人性化小鼠中未发现可复制的病毒。低水平的免疫活化和衰退的HIV-1特异性体液和细胞免疫反应表明没有持续抗原产生。在分析性治疗中断四年后,缺乏病毒反弹和HIV-1抗原持续的免疫学相关因素是CCR5Δ32/Δ32 HSCT治疗后HIV-1治愈的有力证据。©2023 年。作者。
Despite scientific evidence originating from two patients published to date that CCR5Δ32/Δ32 hematopoietic stem cell transplantation (HSCT) can cure human immunodeficiency virus type 1 (HIV-1), the knowledge of immunological and virological correlates of cure is limited. Here we characterize a case of long-term HIV-1 remission of a 53-year-old male who was carefully monitored for more than 9 years after allogeneic CCR5Δ32/Δ32 HSCT performed for acute myeloid leukemia. Despite sporadic traces of HIV-1 DNA detected by droplet digital PCR and in situ hybridization assays in peripheral T cell subsets and tissue-derived samples, repeated ex vivo quantitative and in vivo outgrowth assays in humanized mice did not reveal replication-competent virus. Low levels of immune activation and waning HIV-1-specific humoral and cellular immune responses indicated a lack of ongoing antigen production. Four years after analytical treatment interruption, the absence of a viral rebound and the lack of immunological correlates of HIV-1 antigen persistence are strong evidence for HIV-1 cure after CCR5Δ32/Δ32 HSCT.© 2023. The Author(s).