{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T07:41:03Z","timestamp":1789026063122,"version":"build-2803163510"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005743","name":"Universit\u00e0 Cattolica del Sacro Cuore","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005743","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J. Neurovirol."],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>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\u201390% 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.<\/jats:p>","DOI":"10.1007\/s13365-025-01243-0","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T18:56:26Z","timestamp":1739991386000},"page":"109-115","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Prolonged survival in HIV-associated Progressive Multifocal Leukoencephalopathy treated with Pembrolizumab: a case series on treatment and long-term follow-up"],"prefix":"10.1007","volume":"31","author":[{"given":"Marta","family":"Chiuchiarelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Micheli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco Vladimiro","family":"Segala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Giuliano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Del Giacomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Dusina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Matteini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Frondizi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Gaudino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Lisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Cimini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosaria","family":"Santangelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Agrati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Torti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Cingolani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,19]]},"reference":[{"issue":"11","key":"1243_CR1","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1111\/hiv.1354213","volume":"24","author":"J Ambrosioni","year":"2023","unstructured":"Ambrosioni J, Levi L, Alagaratnam J et al (2023) Major revision version 12.0 of the European AIDS Clinical Society guidelines 2023. HIV Med 24(11):1126\u20131136. https:\/\/doi.org\/10.1111\/hiv.1354213","journal-title":"HIV Med"},{"key":"1243_CR2","unstructured":"Assistance Publique - H\u00f4pitaux de Paris (n.d.) Pembrolizumab in progressive multifocal leukoencephalopathy (PML) in immunocompromised patients without HIV infection (PENALTY). ClinicalTrials.gov. Retrieved February 12, 2025, from https:\/\/clinicaltrials.gov\/study\/NCT06276504"},{"issue":"1","key":"1243_CR3","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1007\/s13365-022-01103-1","volume":"29","author":"Bel\u00e9n Baena-\u00c1lvarez","year":"2022","unstructured":"Baena-\u00c1lvarez Bel\u00e9n et al (2022) Progressive Multifocal Leukoencephalopathy, Advanced Ductal Breast Carcinoma, Systemic Sclerosis, and Checkpoint Inhibitors: A Therapeutic Dilemma. J Neurovirol 29(1):116\u2013119. https:\/\/doi.org\/10.1007\/s13365-022-01103-1","journal-title":"J Neurovirol"},{"issue":"2","key":"1243_CR4","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1007\/s13365-022-01059-2","volume":"28","author":"F Boesl","year":"2022","unstructured":"Boesl F et al (2022) Sequential Treatment of Progressive Multifocal Leukoencephalopathy with Intravenous Immunoglobulins and Pembrolizumab. J Neurovirol 28(2):335\u2013338. https:\/\/doi.org\/10.1007\/s13365-022-01059-2","journal-title":"J Neurovirol"},{"key":"1243_CR5","doi-asserted-by":"publisher","first-page":"1597","DOI":"10.1056\/nejmoa1815039","volume":"380","author":"I Cortese","year":"2019","unstructured":"Cortese I et al (2019) Pembrolizumab treatment for Progressive Multifocal Leukoencephalopathy. N Engl J Med 380:1597\u20131605. https:\/\/doi.org\/10.1056\/nejmoa1815039","journal-title":"N Engl J Med"},{"key":"1243_CR6","doi-asserted-by":"crossref","unstructured":"Hoang E, Bartlett NL, Goyal MS, Schmidt RE, Clifford DB (2019) Progressive multifocal leukoencephalopathy treated with nivolumab. J Neurovirol 25(2):284\u20137.\u00f9","DOI":"10.1007\/s13365-019-00738-x"},{"issue":"6","key":"1243_CR7","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1007\/s13365-020-00899-0","volume":"26","author":"A Holmes","year":"2020","unstructured":"Holmes A et al (2020) Progressive Multifocal Leukoencephalopathy Associated with a Lymphoproliferative Disorder Treated with Pembrolizumab. J Neurovirol 26(6):961\u2013963. https:\/\/doi.org\/10.1007\/s13365-020-00899-0","journal-title":"J Neurovirol"},{"key":"1243_CR8","doi-asserted-by":"publisher","first-page":"109","DOI":"10.2147\/DNND.S203405","volume":"9","author":"M Kartau","year":"2019","unstructured":"Kartau M, Sipil\u00e4 JO, Auvinen E, Palom\u00e4ki M, Verkkoniemi-Ahola A (2019) Progressive Multifocal Leukoencephalopathy: current insights. Degener Neurol Neuromuscul Dis 9:109\u2013121. https:\/\/doi.org\/10.2147\/DNND.S203405","journal-title":"Degener Neurol Neuromuscul Dis"},{"key":"1243_CR9","doi-asserted-by":"publisher","first-page":"3814","DOI":"10.1111\/ene.15021","volume":"28","author":"N Lambert","year":"2021","unstructured":"Lambert N et al (2021) Immune Checkpoint Inhibitors for Progressive Multifocal Leukoencephalopathy: Identifying Relevant Outcome Factors. Eur J Neurol 28:3814\u20133819. https:\/\/doi.org\/10.1111\/ene.15021","journal-title":"Eur J Neurol"},{"key":"1243_CR10","doi-asserted-by":"publisher","first-page":"175628642199368","DOI":"10.1177\/1756286421993684","volume":"14","author":"N M\u00f6hn","year":"2021","unstructured":"M\u00f6hn N et al (2021) PD-1-inhibitor pembrolizumab for treatment of Progressive Multifocal Leukoencephalopathy. Ther Adv Neurol Disord 14:175628642199368. https:\/\/doi.org\/10.1177\/1756286421993684","journal-title":"Ther Adv Neurol Disord"},{"key":"1243_CR11","unstructured":"National Library of Medicine (n.d.) Treatment of PD-1 inhibitor in AIDS-associated PML (TPAP). ClinicalTrials.gov. https:\/\/clinicaltrials.gov\/study\/NCT04091932"},{"key":"1243_CR12","unstructured":"Panel on Antiretroviral Guidelines for Adults and Adolescents (n.d.) Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Department of Health and Human Services. https:\/\/clinicalinfo.hiv.gov\/en\/guidelines\/adult-and-adolescent-arv. Accesed 9 Sep 2024"},{"issue":"5","key":"1243_CR13","doi-asserted-by":"publisher","first-page":"970","DOI":"10.3390\/v14050970","volume":"14","author":"C Pinnetti","year":"2022","unstructured":"Pinnetti C et al (2022) Use of Pembrolizumab for Treatment of Progressive Multifocal Leukoencephalopathy in People Living with HIV. Viruses. 14(5):970. https:\/\/doi.org\/10.3390\/v14050970","journal-title":"Viruses"},{"key":"1243_CR14","doi-asserted-by":"publisher","first-page":"S95","DOI":"10.1016\/j.cmi.2018.01.030","volume":"24","author":"G Redelman-Sidi","year":"2018","unstructured":"Redelman-Sidi G et al (2018) ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the Safety of Targeted and Biological Therapies: An Infectious Diseases Perspective (Immune Checkpoint Inhibitors, Cell Adhesion Inhibitors, Sphingosine-1-Phosphate Receptor Modulators and Proteasome Inhibitors). Clin Microbiol Infect 24:S95\u2013107. https:\/\/doi.org\/10.1016\/j.cmi.2018.01.030","journal-title":"Clin Microbiol Infect"},{"issue":"3","key":"1243_CR15","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1097\/QAI.0b013e31825a313c","volume":"60","author":"CS Tan","year":"2012","unstructured":"Tan CS, Bord E, Broge TA Jr, Glotzbecker B, Mills H, Gheuens S et al (2012) Increased program cell death-1 expression on T lympho- cytes of patients with progressive multifocal leukoencephalopathy. J Acquir Immune Defic Syndr 60(3):244\u2013248","journal-title":"J Acquir Immune Defic Syndr"},{"key":"1243_CR16","doi-asserted-by":"publisher","first-page":"578248","DOI":"10.1016\/j.jneuroim.2023.5782","volume":"385","author":"K Varmpompiti","year":"2023","unstructured":"Varmpompiti K, Westwood AJ, Ben-Joseph A, Sibtain N, Ibrahim MAA, Stanton B, Zuckerman M, Hadden R, Ritter LM (2023) Progressive multifocal leukoencephalopathy secondary to idiopathic CD4 lymphocytopenia treated with pembrolizumab. J Neuroimmunol 385:578248. https:\/\/doi.org\/10.1016\/j.jneuroim.2023.5782","journal-title":"J Neuroimmunol"},{"key":"1243_CR17","doi-asserted-by":"publisher","unstructured":"Wicklein R et al (2021) Combined treatment with Pembrolizumab and allogenic BK virus-specific T cells in Progressive Multifocal Leukoencephalopathy. Neurol Neuroimmunol Neuroinflammation 8(5). https:\/\/doi.org\/10.1212\/nxi.0000000000001042","DOI":"10.1212\/nxi.0000000000001042"},{"issue":"3","key":"1243_CR18","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1007\/s13365-023-01180-w","volume":"29","author":"L Yang","year":"2023","unstructured":"Yang L et al (2023) Clinical and radiological outcomes in progressive multifocal leukoencephalopathy treated with pembrolizumab: a case series. J Neurovirol 29(3):456\u2013462. https:\/\/doi.org\/10.1007\/s13365-023-01180-w","journal-title":"J Neurovirol"}],"container-title":["Journal of NeuroVirology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13365-025-01243-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13365-025-01243-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13365-025-01243-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T13:41:37Z","timestamp":1749044497000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13365-025-01243-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,19]]},"references-count":18,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["1243"],"URL":"https:\/\/doi.org\/10.1007\/s13365-025-01243-0","relation":{},"ISSN":["1355-0284","1538-2443"],"issn-type":[{"value":"1355-0284","type":"print"},{"value":"1538-2443","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,19]]},"assertion":[{"value":"27 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 February 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 February 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 February 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have obtained consent to publish this manuscript from all involved parties, including co-authors and contributors.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}