{"title":"干细胞移植和异体免疫:治疗后控制还是治愈艾滋病毒?","authors":"Megan Cleary, Lishomwa C Ndhlovu, Jonah B Sacha","doi":"10.1097/COH.0000000000000892","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose of review: </strong>Long-lasting HIV remission has been reported in a small group of people with HIV (PWH) following allogenic hematopoietic stem cell transplants (HSCT) for the treatment of hematologic malignancies. While the mechanisms of HIV remission following release from antiretroviral therapy (ART) were not initially known, subsequent findings from clinical cases and preclinical nonhuman primate studies have implicated mechanisms of clearance. Here, we review the six currently published human cases of long-term ART-free HIV remission.</p><p><strong>Recent findings: </strong>Since the first report of ART-free HIV remission following HSCT, five subsequent cases of HSCT-induced sustained HIV remission have been published. While the pre- and posttransplant treatment conditions vary greatly, all but one received cells from donors homozygous for a 32 bp deletion in the gene that encodes CCR5 ( ccr5Δ32 ), the major HIV coreceptor. Studies in nonhuman primates and the newest published individual suggest that while CCR5 deficiency can protect donor cells from infection early posttransplant, it is not required for long term remission, as ablation of the viral reservoir is likely due to allogeneic immunity mediating a graft-versus-reservoir response.</p><p><strong>Summary: </strong>Studies of HSCT in PLWH and simian immunodeficiency virus (SIV)-infected monkeys show that those with durable remission are likely cured, demonstrated by complete ablation of the replication-competent HIV reservoir, gradual loss of anti-HIV immunity, and greater than 5 years of aviremia.</p>","PeriodicalId":93966,"journal":{"name":"Current opinion in HIV and AIDS","volume":" ","pages":"86-91"},"PeriodicalIF":0.0000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11620935/pdf/","citationCount":"0","resultStr":"{\"title\":\"Stem cell transplantation and allogeneic immunity: post treatment control or HIV cure?\",\"authors\":\"Megan Cleary, Lishomwa C Ndhlovu, Jonah B Sacha\",\"doi\":\"10.1097/COH.0000000000000892\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose of review: </strong>Long-lasting HIV remission has been reported in a small group of people with HIV (PWH) following allogenic hematopoietic stem cell transplants (HSCT) for the treatment of hematologic malignancies. While the mechanisms of HIV remission following release from antiretroviral therapy (ART) were not initially known, subsequent findings from clinical cases and preclinical nonhuman primate studies have implicated mechanisms of clearance. Here, we review the six currently published human cases of long-term ART-free HIV remission.</p><p><strong>Recent findings: </strong>Since the first report of ART-free HIV remission following HSCT, five subsequent cases of HSCT-induced sustained HIV remission have been published. While the pre- and posttransplant treatment conditions vary greatly, all but one received cells from donors homozygous for a 32 bp deletion in the gene that encodes CCR5 ( ccr5Δ32 ), the major HIV coreceptor. Studies in nonhuman primates and the newest published individual suggest that while CCR5 deficiency can protect donor cells from infection early posttransplant, it is not required for long term remission, as ablation of the viral reservoir is likely due to allogeneic immunity mediating a graft-versus-reservoir response.</p><p><strong>Summary: </strong>Studies of HSCT in PLWH and simian immunodeficiency virus (SIV)-infected monkeys show that those with durable remission are likely cured, demonstrated by complete ablation of the replication-competent HIV reservoir, gradual loss of anti-HIV immunity, and greater than 5 years of aviremia.</p>\",\"PeriodicalId\":93966,\"journal\":{\"name\":\"Current opinion in HIV and AIDS\",\"volume\":\" \",\"pages\":\"86-91\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11620935/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current opinion in HIV and AIDS\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1097/COH.0000000000000892\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/25 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current opinion in HIV and AIDS","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1097/COH.0000000000000892","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/25 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
审查目的:据报道,一小部分艾滋病病毒感染者(PWH)在接受异基因造血干细胞移植(HSCT)治疗血液系统恶性肿瘤后,艾滋病病毒得到了长期缓解。虽然最初并不清楚抗逆转录病毒疗法(ART)解除后艾滋病毒缓解的机制,但随后从临床病例和非人灵长类动物临床前研究中发现了清除机制。在此,我们回顾了目前已发表的六例长期无抗逆转录病毒疗法的人类艾滋病缓解病例:自首次报道造血干细胞移植后无抗逆转录病毒疗法的艾滋病缓解以来,又有五例造血干细胞移植诱导的艾滋病持续缓解病例发表。虽然移植前和移植后的治疗条件差别很大,但除一例外,其他所有病例的细胞都来自于编码 HIV 主要核心受体 CCR5(ccr5Δ32)的基因缺失 32 bp 的同源供体。对非人灵长类动物的研究和最新发表的个体研究表明,虽然 CCR5 缺失可以保护供体细胞在移植后早期免受感染,但长期缓解并不需要 CCR5 缺失,因为病毒库的消减可能是由于异体免疫介导的移植物对病毒库的反应。摘要:对 PLWH 和猿猴免疫缺陷病毒(SIV)感染者进行造血干细胞移植的研究表明,那些获得持久缓解的患者很可能已经痊愈,具体表现为具有复制能力的 HIV 病毒库被完全消融、抗 HIV 免疫力逐渐丧失,以及出现超过 5 年的无病毒血症。
Stem cell transplantation and allogeneic immunity: post treatment control or HIV cure?
Purpose of review: Long-lasting HIV remission has been reported in a small group of people with HIV (PWH) following allogenic hematopoietic stem cell transplants (HSCT) for the treatment of hematologic malignancies. While the mechanisms of HIV remission following release from antiretroviral therapy (ART) were not initially known, subsequent findings from clinical cases and preclinical nonhuman primate studies have implicated mechanisms of clearance. Here, we review the six currently published human cases of long-term ART-free HIV remission.
Recent findings: Since the first report of ART-free HIV remission following HSCT, five subsequent cases of HSCT-induced sustained HIV remission have been published. While the pre- and posttransplant treatment conditions vary greatly, all but one received cells from donors homozygous for a 32 bp deletion in the gene that encodes CCR5 ( ccr5Δ32 ), the major HIV coreceptor. Studies in nonhuman primates and the newest published individual suggest that while CCR5 deficiency can protect donor cells from infection early posttransplant, it is not required for long term remission, as ablation of the viral reservoir is likely due to allogeneic immunity mediating a graft-versus-reservoir response.
Summary: Studies of HSCT in PLWH and simian immunodeficiency virus (SIV)-infected monkeys show that those with durable remission are likely cured, demonstrated by complete ablation of the replication-competent HIV reservoir, gradual loss of anti-HIV immunity, and greater than 5 years of aviremia.