{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:13:49Z","timestamp":1791224029727,"version":"4.1.0"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mr. Javier Moreno","award":["II040141"],"award-info":[{"award-number":["II040141"]}]},{"name":"Fondo de Investigaci\u00f3n Sanitaria","award":["PI24\/00816"],"award-info":[{"award-number":["PI24\/00816"]}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["INFECG 30.S.N.\/2024"],"award-info":[{"award-number":["INFECG 30.S.N.\/2024"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100022335","name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer","doi-asserted-by":"crossref","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100022335","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010877","name":"ViiV Healthcare","doi-asserted-by":"crossref","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100010877","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Janssen","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Gilead","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Fingolimod, a treatment for multiple sclerosis (MS), decreases autoreactive lymphocytes by lymph node sequestration.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , fingolimod decreases HIV-1 infection and viral reservoir (VR) through SAMHD1 phosphorylation inhibition and reducing lymphocyte activation and CD4 expression. We identified an exceptional MS patient infected with HIV-1 (HIV+\u2009MS+) while on fingolimod therapy and we have analyzed its impact on HIV-1 infection\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>ex vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The case was the HIV+\u2009MS+ patient. Controls were 20 PWH (HIV+\u2009MS-), five HIV-negative donors (HIV-MS) and three HIV-negative MS patients treated with fingolimod (HIV-MS+), as the case reported. VR was quantified by IPDA and HIV-1 intracellular RNAs (icRNAs) by ddPCR in peripheral blood CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cells. CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cells were infected\n                      <jats:italic>in vitro<\/jats:italic>\n                      with an NL4.3-Renilla strain. Immunophenotype, activation markers and phosphorylated SAMHD1 levels were determined by flow cytometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>\n                      At diagnosis, HIV+\u2009MS+ viral load was nine-fold lower than HIV+\u2009MS- treated at similar Fiebig stage. One year after ART, HIV+\u2009MS+ showed lower intact and defective VR than the HIV+\u2009MS- control group (28-and six-fold decrease respectively). After three years on ART no intact proviruses were detected in HIV+\u2009MS+\u2009. HIV-1\n                      <jats:italic>in vitro<\/jats:italic>\n                      infection was decreased in HIV+\u2009MS+ and HIV- MS\u2009+\u2009vs HIV+\u2009MS- and HIV-MS-. CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cells levels from fingolimod treated patients were lower and showed decreased CD4 expression, lymphocyte activation and SAMHD1 phosphorylation vs HIV- MS-. icRNAs were significantly increased after T-cell activation in the HIV+\u2009MS-, while they were barely detected at resting and activated HIV+\u2009MS+\u2009CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We describe a strong restriction to HIV-1 infection and replication\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>ex vivo<\/jats:italic>\n                      leading to indetectable intact VR in HIV+\u2009MS+ after three years of ART. Potential mechanisms of restriction are CD4 downregulation, T-cell activation inhibition, and SAMHD1 activity enhancement.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.ppat.1014266","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T17:36:48Z","timestamp":1780508208000},"page":"e1014266","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Fingolimod increases cellular resistance to HIV-1 infection and limits viral reservoir size in peripheral CD4+ 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M.","family":"Mir\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Mallolas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Albend\u00edn-Iglesias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Alcam\u00ed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9142-812X","authenticated-orcid":true,"given":"Sonsoles","family":"S\u00e1nchez-Palomino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"issue":"2","key":"ppat.1014266.ref001","doi-asserted-by":"crossref","first-page":"482","DOI":"10.3390\/cells9020482","article-title":"T Helper Cells: The modulators of 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