Pembrolizumab治疗hiv相关进行性多灶性白质脑病的延长生存期:治疗和长期随访的病例系列

IF 1.9 4区 医学 Q3 NEUROSCIENCES
Journal of NeuroVirology Pub Date : 2025-04-01 Epub Date: 2025-02-19 DOI:10.1007/s13365-025-01243-0
Marta Chiuchiarelli, Giulia Micheli, Francesco Vladimiro Segala, Gabriele Giuliano, Paola Del Giacomo, Alex Dusina, Elena Matteini, Federico Frondizi, Simona Gaudino, Francesca Lisi, Eleonora Cimini, Rosaria Santangelo, Chiara Agrati, Carlo Torti, Antonella Cingolani
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引用次数: 0

摘要

进行性多灶性脑白质病(PML)是一种罕见的由人多瘤病毒JC病毒引起的中枢神经系统(CNS)机会性感染,HIV感染者(PLWH)死亡率高,除抗逆转录病毒联合治疗(cART)外,尚无有效的特异性治疗方法。Pembrolizumab是T细胞上程序性细胞死亡蛋白1 (PD-1)受体的抑制剂,其使用与病毒清除率降低有关。本研究的目的是评估pembrolizumab治疗PML对PLWH的临床病程。我们报告了连续4例PLWH的临床和放射学证据表明脑脊液(CSF)中检测到PML和JCV-DNA。Pembrolizumab与cART一起应用于所有4名PLWH患者。在医疗方案结束时进行放射和实验室随访。在临床上,4名PLWH患者中有3名表现出神经功能缺陷的改善,部分恢复了失去的功能,他们分别在3.5年,14个月和9个月时存活;第四名患者在治疗后不久因呼吸系统恶化死亡。在所有完成治疗的PLWH中,观察到特异性PD-1活性降低了约80-90%。在4例PLWH患者中,3例患者的生存时间延长,影像学表现稳定,临床改善,获得性缺陷部分恢复。此外,还观察到抗pd -1表达的下降,这表明治疗与成功之间存在联系。鉴于现有文献中样本量小且证据相互矛盾,需要进一步调查以评估其有效性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Prolonged survival in HIV-associated Progressive Multifocal Leukoencephalopathy treated with Pembrolizumab: a case series on treatment and long-term follow-up.

Prolonged survival in HIV-associated Progressive Multifocal Leukoencephalopathy treated with Pembrolizumab: a case series on treatment and long-term follow-up.

Progressive Multifocal Leukoencephalopathy (PML) is a rare opportunistic infection of the central nervous system (CNS) caused by human polyomavirus JC virus, with high mortality rate in people living with HIV (PLWH), without an effective specific treatment beside combined antiretroviral therapy (cART). The use of Pembrolizumab, an inhibitor of the Programmed cell death protein 1 (PD-1) receptor on T cells, has been associated with decreased viral clearance. Aim of this study is to evaluate clinical course of PLWH affected by PML treated with pembrolizumab. We report four consecutive PLWH with clinical and radiological evidence of PML and JCV-DNA detection in cerebrospinal fluid (CSF). Pembrolizumab was administered to all four PLWH alongside cART. Radiological and laboratory follow-up were performed at the end of the medical protocol. Clinically, 3 out of 4 PLWH showed an improvement in neurological deficits, partially reacquiring the lost functions, and they are alive at 3.5 years, 14 months, and 9 months, respectively; the fourth patient died shortly after treatment due to worsening respiratory conditions. In all the PLWH completing treatment, a decrease of about 80-90% of the specific PD-1 activity was observed. Prolonged survival and stabilization of radiological findings have been observed, along with clinical improvement and partial recovery of acquired deficits in 3 out of 4 PLWH. In addition, a decrease in anti-PD-1 expression has also been observed, suggesting a link between the therapy and the success achieved. Given the small sample and conflicting evidence in the existing literature, further investigation is needed to assess its effectiveness.

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来源期刊
Journal of NeuroVirology
Journal of NeuroVirology 医学-病毒学
CiteScore
6.60
自引率
3.10%
发文量
77
审稿时长
6-12 weeks
期刊介绍: The Journal of NeuroVirology (JNV) provides a unique platform for the publication of high-quality basic science and clinical studies on the molecular biology and pathogenesis of viral infections of the nervous system, and for reporting on the development of novel therapeutic strategies using neurotropic viral vectors. The Journal also emphasizes publication of non-viral infections that affect the central nervous system. The Journal publishes original research articles, reviews, case reports, coverage of various scientific meetings, along with supplements and special issues on selected subjects. The Journal is currently accepting submissions of original work from the following basic and clinical research areas: Aging & Neurodegeneration, Apoptosis, CNS Signal Transduction, Emerging CNS Infections, Molecular Virology, Neural-Immune Interaction, Novel Diagnostics, Novel Therapeutics, Stem Cell Biology, Transmissable Encephalopathies/Prion, Vaccine Development, Viral Genomics, Viral Neurooncology, Viral Neurochemistry, Viral Neuroimmunology, Viral Neuropharmacology.
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