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使用野生型CCR5供体细胞进行异基因造血干细胞移植后实现持续的HIV缓解。

Sustained HIV remission after allogeneic hematopoietic stem cell transplantation with wild-type CCR5 donor cells.

作者信息

Sáez-Cirión Asier, Mamez Anne-Claire, Avettand-Fenoel Véronique, Nabergoj Mitja, Passaes Caroline, Thoueille Paul, Decosterd Laurent, Hentzien Maxime, Perdomo-Celis Federico, Salgado Maria, Nijhuis Monique, Mélard Adeline, Gardiennet Elise, Lorin Valérie, Monceaux Valérie, Chapel Anaïs, Gourvès Maël, Lechartier Marine, Mouquet Hugo, Wensing Annemarie, Martinez-Picado Javier, Yerly Sabine, Rougemont Mathieu, Calmy Alexandra

机构信息

Viral Reservoirs and Immune Control Unit, Université Paris Cité, Institut Pasteur, Paris, France.

HIV Inflammation and Persistence Unit, Université Paris Cité, Institut Pasteur, Paris, France.

出版信息

Nat Med. 2024 Dec;30(12):3544-3554. doi: 10.1038/s41591-024-03277-z. Epub 2024 Sep 2.

Abstract

HIV cure has been reported for five individuals who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with cells from CCR5Δ32 homozygous donors. By contrast, viral rebound has occurred in other people living with HIV who interrupted antiretroviral treatment after undergoing allo-HSCT, with cells mostly from wild-type CCR5 donors. Here we report the case of a male individual who has achieved durable HIV remission following allo-HSCT with cells from an unrelated HLA-matched (9 of 10 matching for HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 alleles) wild-type CCR5 donor to treat an extramedullary myeloid tumor. To date, plasma viral load has remained undetectable for 32 months after the interruption of antiretroviral treatment. Treatment with ruxolitinib has been maintained during this period to treat chronic graft-versus-host disease. Low levels of proviral DNA were detected sporadically after allo-HSCT, including defective but not intact HIV DNA. No virus could be amplified in cultures of CD4 T cells obtained after antiretroviral treatment interruption, while CD4 T cells remained susceptible to HIV-1 infection in vitro. Declines in HIV antibodies and undetectable HIV-specific T cell responses further corroborate the absence of viral rebound after antiretroviral treatment interruption. These results suggest that HIV remission could be achieved in the context of allo-HSCT with wild-type CCR5.

摘要

已有报道称,5名接受来自CCR5Δ32纯合供体的异基因造血干细胞移植(allo-HSCT)的个体实现了HIV治愈。相比之下,其他接受allo-HSCT后中断抗逆转录病毒治疗的HIV感染者出现了病毒反弹,这些供体细胞大多来自野生型CCR5供体。在此,我们报告了一例男性个体的病例,该个体在接受来自一名无关的HLA匹配(HLA-A、HLA-B、HLA-C、HLA-DRB1和HLA-DQB1等位基因10个中有9个匹配)的野生型CCR5供体的细胞进行allo-HSCT以治疗髓外髓样肿瘤后,实现了持久的HIV缓解。迄今为止,在中断抗逆转录病毒治疗后32个月,血浆病毒载量一直检测不到。在此期间,一直使用鲁索替尼进行治疗以治疗慢性移植物抗宿主病。allo-HSCT后偶尔检测到低水平的前病毒DNA,包括有缺陷但完整的HIV DNA。在中断抗逆转录病毒治疗后获得的CD4 T细胞培养物中无法扩增出病毒,而CD4 T细胞在体外仍易受HIV-1感染。HIV抗体水平下降以及无法检测到HIV特异性T细胞反应进一步证实了中断抗逆转录病毒治疗后没有病毒反弹。这些结果表明,在使用野生型CCR5进行allo-HSCT的情况下可以实现HIV缓解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb9/11645271/41ee7cfec8d5/41591_2024_3277_Fig1_HTML.jpg

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