夏里特-柏林医科大学Olaf Penack小组宣布他们研制了杂合子CCR5Δ32干细胞移植后HIV-1持续缓解。该项研究成果发表在2025年12月1日出版的《自然》上。

该课题组人员为这一概念转变提供了新的证据，报告了具有功能活性CCR5的同种异体细胞移植后异常长时间的无治疗HIV缓解。一名携带HIV病毒的杂合子CCR5野生型/Δ32男性接受了来自HLA匹配的非亲属杂合子CCR5野生型/Δ32供体的同种异体SCT治疗急性髓系白血病。在接受同种细胞移植三年后，患者停止了抗逆转录病毒治疗。

迄今为止，在血浆HIV RNA检测不到的情况下，HIV缓解已经持续了六年多。水库分析显示移植前存在完整的前HIV病毒，但同种异体SCT后血液或肠组织中没有复制能力的病毒。HIV特异性抗体和T细胞反应的下降或缺失支持病毒活性的缺失。移植时的高抗体依赖性细胞毒性（ADCC）活性可能有助于HIV库清除。这些结果表明CCR5Δ32介导的HIV耐药性对于持久的缓解不是必需的，强调了有效减少病毒库在HIV治愈策略中的重要性。

研究人员表示，艾滋病毒治愈极为罕见，自该流行病开始以来，估计有8800万人感染了艾滋病毒，其中只有6例得到了治愈。成功的治疗，包括开创性的柏林病人，仅限于接受同种异体干细胞移植（allo-SCT）治疗血液病癌症的个体。长期以来，具有罕见纯合子CCR5 Δ32突变的干细胞供体的HIV抗性被认为是无需抗逆转录病毒治疗（ART）的HIV缓解的主要机制，但最近的报道强调CCR5独立机制是HIV治愈的重要贡献者。

附：英文原文

Title: Sustained HIV-1 remission after heterozygous CCR5Δ32 stem cell transplantation

Author: Gaebler, Christian, Kor, Samad, Allers, Kristina, Perotti, Michela, Mwangi, David, Meixenberger, Karolin, Hanke, Kirsten, Trenkner, Timo, Kraus, Tom, Sha, Yequin, Arentowicz, Carmen, Odidika, Stanley, Grahn, Nikolai, Scheck, Rachel, Perkins, Naomi, Pardons, Marion, Igbokwe, Vanessa, Corman, Victor, Burmeister, Thomas, Blau, Olga, Src, Glstan, Pru, Axel, Schneider, Christian G., Klausen, Gerd, Sauter, Jrgen, Klein, Florian, Sander, Leif E., Hofmann, Jrg, Vuong, Lam, Bullinger, Lars, Penter, Livius, Gruell, Henning, Reeves, Daniel B., Schommers, Philipp, Hoelzemer, Angelique, Obermeier, Martin, Blau, Igor W., Schneider, Thomas, Penack, Olaf

Issue&Volume: 2025-12-01

Abstract: HIV cure is exceptionally rare, documented in only six cases among the estimated 88 million individuals who have acquired HIV since the epidemic's onset1–6. Successful cures, including the pioneering Berlin patient, are limited to individuals receiving allogeneic stem cell transplants (allo-SCT) for hematological cancers. HIV resistance from stem cell donors with the rare homozygous CCR5 Δ32 mutation was long considered the main mechanism for HIV remission without antiretroviral therapy (ART), but recent reports highlight CCR5-independent mechanisms as important contributors to HIV cure6–8. Here, we provide new evidence for this conceptual shift, reporting exceptionally long, treatment-free HIV remission following allo-SCT with functionally active CCR5. A heterozygous CCR5 wild-type/Δ32 male living with HIV received allo-SCT from an HLA-matched unrelated heterozygous CCR5 wild-type/Δ32 donor as treatment for acute myeloid leukemia. Three years after allo-SCT, the patient discontinued ART. To date, HIV remission has been sustained for over six years with undetectable plasma HIV RNA. Reservoir analysis revealed intact proviral HIV before transplantation, but no replication-competent virus in blood or intestinal tissues after allo-SCT. Declining or absent HIV-specific antibody and T cell responses support the absence of viral activity. High antibody-dependent cellular cytotoxicity (ADCC) activity at the time of transplantation may have contributed to HIV reservoir clearance. These results demonstrate that CCR5Δ32-mediated HIV resistance is not essential for durable remission, underscoring the importance of effective viral reservoir reductions in HIV cure strategies.

DOI: 10.1038/s41586-025-09893-0

Source: https://www.nature.com/articles/s41586-025-09893-0