Chiuchiarelli Marta, Micheli Giulia, Segala Francesco Vladimiro, Giuliano Gabriele, Del Giacomo Paola, Dusina Alex, Matteini Elena, Frondizi Federico, Gaudino Simona, Lisi Francesca, Cimini Eleonora, Santangelo Rosaria, Agrati Chiara, Torti Carlo, Cingolani Antonella
Dipartimento di Sicurezza e Bioetica - Sezione di Malattie Infettive, Università Cattolica del Sacro Cuore, Rome, Italy.
Clinical Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy.
J Neurovirol. 2025 Feb 19. doi: 10.1007/s13365-025-01243-0.
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.
进行性多灶性白质脑病（PML）是一种由人多瘤病毒JC病毒引起的罕见的中枢神经系统（CNS）机会性感染，在艾滋病毒感染者（PLWH）中死亡率很高，除联合抗逆转录病毒疗法（cART）外没有有效的特异性治疗方法。程序性细胞死亡蛋白1（PD-1）受体抑制剂帕博利珠单抗的使用与病毒清除率降低有关。本研究的目的是评估接受帕博利珠单抗治疗的PML感染PLWH的临床病程。我们报告了4例连续的PLWH，他们具有PML的临床和影像学证据以及脑脊液（CSF）中JCV-DNA检测阳性。所有4例PLWH在接受cART的同时均接受了帕博利珠单抗治疗。在医疗方案结束时进行了影像学和实验室随访。临床上，4例PLWH中有3例神经功能缺损有所改善，部分恢复了丧失的功能，他们分别在3.5年、14个月和9个月时存活；第四例患者在治疗后不久因呼吸状况恶化死亡。在所有完成治疗的PLWH中，观察到特异性PD-1活性下降了约80-90%。观察到患者生存期延长、影像学表现稳定，4例PLWH中有3例临床症状改善且获得性缺损部分恢复。此外，还观察到抗PD-1表达下降，提示该治疗与取得的疗效之间存在联系。鉴于样本量小且现有文献证据相互矛盾，需要进一步研究以评估其有效性。
