{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T07:41:02Z","timestamp":1789026062426,"version":"build-2803163510"},"reference-count":26,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T00:00:00Z","timestamp":1651708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Progressive Multifocal Leukoencephalopathy (PML) is a demyelinating disease occurring in advanced HIV infection, caused by the reactivation of poliomavirus JC (JCV). The use of pembrolizumab for treatment is based on the inhibition of programmed cell death protein 1 (PD-1), potentially improving the anti JCV-specific response. We used pembrolizumab with combined antiretroviral treatment (cART) on a compassionate-use basis. At each administration, clinical evaluation, MRI and laboratory testing, including CD3, CD4, CD8, PD-1 markers, HIV-RNA and JCV-DNA in cerebrospinal fluid (CSF)\/plasma pairs, were performed. The JCV-specific T cell response was analysed by Elispot assay. This study included five HIV patients: four male, median age 43 years (29\u201352), median CD4 and CD8 count 150 (15\u2013158) and 973 (354\u20131250) cell\/mm3, respectively; median JCV-DNA and HIV-RNA in CSF\/plasma pairs 9.540\/1.503 cps\/mL and 2.230\/619 cp\/mL, respectively. Overall, patients received between two and seven doses of pembrolizumab. After treatment, we observed JCV-DNA reduction and PD-1 down-regulation both in CSF and in plasma (high in circulating CD4 and CD8 at baseline), which remained stable at low levels in all patients. Three out of five patients showed stability of clinical picture and neuroimaging, while two others died. More data are needed in order to identify predictors of response to therapy.<\/jats:p>","DOI":"10.3390\/v14050970","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T02:46:39Z","timestamp":1651805199000},"page":"970","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Use of Pembrolizumab for Treatment of Progressive Multifocal Leukoencephalopathy in People Living with HIV"],"prefix":"10.3390","volume":"14","author":[{"given":"Carmela","family":"Pinnetti","sequence":"first","affiliation":[{"name":"HIV\/AIDS Unit, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Cimini","sequence":"additional","affiliation":[{"name":"Cellular Immunology and Pharmacology Laboratory, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6944-0686","authenticated-orcid":false,"given":"Alessandra","family":"Vergori","sequence":"additional","affiliation":[{"name":"HIV\/AIDS Unit, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0240-7504","authenticated-orcid":false,"given":"Valentina","family":"Mazzotta","sequence":"additional","affiliation":[{"name":"HIV\/AIDS Unit, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germana","family":"Grassi","sequence":"additional","affiliation":[{"name":"Cellular Immunology and Pharmacology Laboratory, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Mondi","sequence":"additional","affiliation":[{"name":"HIV\/AIDS Unit, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Forbici","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7063-0222","authenticated-orcid":false,"given":"Alessandra","family":"Amendola","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Grisetti","sequence":"additional","affiliation":[{"name":"HIV\/AIDS Unit, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Baldini","sequence":"additional","affiliation":[{"name":"HIV\/AIDS Unit, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Candela","sequence":"additional","affiliation":[{"name":"HIV\/AIDS Unit, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Casetti","sequence":"additional","affiliation":[{"name":"Cellular Immunology and Pharmacology Laboratory, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7275-7358","authenticated-orcid":false,"given":"Paolo","family":"Campioni","sequence":"additional","affiliation":[{"name":"Radiology Unit, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rosaria","family":"Capobianchi","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5252-0927","authenticated-orcid":false,"given":"Chiara","family":"Agrati","sequence":"additional","affiliation":[{"name":"Cellular Immunology and Pharmacology Laboratory, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2121-4684","authenticated-orcid":false,"given":"Andrea","family":"Antinori","sequence":"additional","affiliation":[{"name":"HIV\/AIDS Unit, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1002\/ana.20933","article-title":"Progressive multifocal leukoencephalopathy revisited: Has the disease outgrown its name?","volume":"60","author":"Koralnik","year":"2006","journal-title":"Ann. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1002\/ana.24371","article-title":"Persistence and pathogenesis of the neurotropic polyomavirus JC","volume":"77","author":"Wollebo","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1128\/CMR.05031-11","article-title":"Molecular Biology, Epidemiology, and Pathogenesis of Progressive Multifocal Leukoencephalopathy, the JC Virus-Induced Demyelinating Disease of the Human Brain","volume":"25","author":"Ferenczy","year":"2012","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"59","DOI":"10.3109\/13550289809113482","article-title":"Progressive Multifocal Leukoencephalopathy in Patients with HIV Infection","volume":"4","author":"Berger","year":"1998","journal-title":"J. Neurovirology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e618","DOI":"10.1212\/NXI.0000000000000618","article-title":"Progressive multifocal leukoencephalopathy: A 25-year retrospective cohort study","volume":"6","author":"Anand","year":"2019","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1089\/aid.2018.0232","article-title":"Not a Disease of the Past: A Case Series of Progressive Multifocal Leukoencephalopathy in the Established Antiretroviral Era","volume":"35","author":"Summers","year":"2019","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"566-e41","DOI":"10.1111\/ene.13906","article-title":"The spectrum of progressive multifocal leukoencephalopathy: A practical approach","volume":"26","author":"Bartsch","year":"2019","journal-title":"Eur. J. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1086\/598335","article-title":"Incidence and Outcome of Progressive Multifocal Leukoencephalopathy over 20 Years of the Swiss HIV Cohort Study","volume":"48","author":"Khanna","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_9","first-page":"1","article-title":"Novel treatments for progressive multifocal leukoencephalopathy","volume":"81","author":"Bennett","year":"2020","journal-title":"Br. J. Hosp. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1056\/NEJMoa1815039","article-title":"Pembrolizumab Treatment for Progressive Multifocal Leukoencephalopathy","volume":"380","author":"Cortese","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1097\/QAI.0b013e31825a313c","article-title":"Increased Program Cell Death\u20131 Expression on T Lymphocytes of Patients With Progressive Multifocal Leukoencephalopathy","volume":"60","author":"Tan","year":"2012","journal-title":"JAIDS J. Acquir. Immune Defic. Syndr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10448","DOI":"10.1128\/JVI.00614-10","article-title":"Rearranged JC Virus Noncoding Control Regions Found in Progressive Multifocal Leukoencephalopathy Patient Samples Increase Virus Early Gene Expression and Replication Rate","volume":"84","author":"Gosert","year":"2010","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1089\/dna.2004.23.858","article-title":"Internalization of Exogenous Human Immunodeficiency Virus-1 Protein, Tat, by KG-1 Oligodendroglioma Cells Followed by Stimulation of DNA Replication Initiated at the JC Virus Origin","volume":"23","author":"Daniel","year":"2004","journal-title":"DNA Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1128\/JVI.02565-14","article-title":"JC Virus Quasispecies Analysis Reveals a Complex Viral Population Underlying Progressive Multifocal Leukoencephalopathy and Supports Viral Dissemination via the Hematogenous Route","volume":"89","author":"Thys","year":"2015","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2013\/197807","article-title":"Polyomavirus JC in the Context of Immunosuppression: A Series of Adaptive, DNA Replication-Driven Recombination Events in the Development of Progressive Multifocal Leukoencephalopathy","volume":"2013","author":"Johnson","year":"2013","journal-title":"Clin. Dev. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1212\/01.WNL.0000096147.47128.7D","article-title":"Comparison of PCR-amplified JC virus control region sequences from multiple brain regions in PML","volume":"61","author":"Yasuda","year":"2003","journal-title":"Neurology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/s41582-020-00427-y","article-title":"Progressive multifocal leukoencephalopathy and the spectrum of JC virus-related disease","volume":"17","author":"Cortese","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"577","DOI":"10.3389\/fimmu.2017.00577","article-title":"Immune Reconstitution Inflammatory Syndrome Unmasking or Worsening AIDS-Related Progressive Multifocal Leukoencephalopathy: A Literature Review","volume":"8","author":"Fournier","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1093\/cid\/ciy074","article-title":"Risk of Progressive Multifocal Leukoencephalopathy in the Combination Antiretroviral Therapy Era in the French Hospital Database on Human Immunodeficiency Virus (ANRS-C4)","volume":"67","author":"Melliez","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1586\/14787210.2015.1029917","article-title":"Opportunistic infections and immune reconstitution inflammatory syndrome in HIV-1-infected adults in the combined antiretroviral therapy era: A comprehensive review","volume":"13","author":"Manzardo","year":"2015","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12981-020-00293-0","article-title":"JC Polyomavirus, progressive multifocal leukoencephalopathy and immune reconstitution inflammatory syndrome: A review","volume":"17","author":"Harypursat","year":"2020","journal-title":"AIDS Res. Ther."},{"key":"ref_22","unstructured":"(2021, June 28). Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV, Available online: https:\/\/clinicalinfo.hiv.gov\/en\/guidelines\/adult-and-adolescent-opportunistic-infection\/progressive-multifocal?view=full."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1212\/01.wnl.0000343510.08643.74","article-title":"PML-IRIS in patients with HIV infection: Clinical manifestations and treatment with steroids","volume":"72","author":"Tan","year":"2009","journal-title":"Neurology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1111\/ene.12963","article-title":"Incidence and prognosis of immune reconstitution inflammatory syndrome in HIV-associated progressive multifocal leucoencephalopathy","volume":"23","author":"Casado","year":"2016","journal-title":"Eur. J. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e000261","DOI":"10.1136\/jitc-2019-000261","article-title":"Late cardiac adverse events in patients with cancer treated with immune checkpoint inhibitors","volume":"8","author":"Dolladille","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1007\/s40264-021-01086-8","article-title":"Immune Checkpoint Inhibitors and Cardiotoxicity: An Analysis of Spontaneous Reports in Eudravigilance","volume":"44","author":"Mascolo","year":"2021","journal-title":"Drug Saf."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/5\/970\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:06:29Z","timestamp":1760137589000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/5\/970"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,5]]},"references-count":26,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["v14050970"],"URL":"https:\/\/doi.org\/10.3390\/v14050970","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,5]]}}}