{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:19:26Z","timestamp":1790777966386,"version":"4.1.0"},"reference-count":39,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"629","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2022,1,26]]},"abstract":"<jats:p>\n            In people living with HIV (PLWH) on antiretroviral therapy (ART), virus persists in a latent form where there is minimal transcription or protein expression. Latently infected cells are a major barrier to curing HIV. Increasing HIV transcription and viral production in latently infected cells could facilitate immune recognition and reduce the pool of infected cells that persist on ART. Given that programmed cell death protein 1 (PD-1) expressing CD4\n            <jats:sup>+<\/jats:sup>\n            T cells are preferentially infected with HIV in PLWH on ART, we aimed to determine whether administration of antibodies targeting PD-1 would reverse HIV latency in vivo. We therefore evaluated the impact of intravenous administration of pembrolizumab every 3 weeks on HIV latency in 32 PLWH and cancer on ART. After the first infusion of anti\u2013PD-1, we observed a median 1.32-fold increase in unspliced HIV RNA and 1.61-fold increase in unspliced RNA:DNA ratio in sorted blood CD4\n            <jats:sup>+<\/jats:sup>\n            T cells compared to baseline. We also observed a 1.65-fold increase in plasma HIV RNA. The frequency of CD4\n            <jats:sup>+<\/jats:sup>\n            T cells with inducible virus evaluated using the\n            <jats:italic>tat\/rev<\/jats:italic>\n            limiting dilution assay was higher after 6 cycles compared to baseline. Phylogenetic analyses of HIV\n            <jats:italic>env<\/jats:italic>\n            sequences in a participant who developed low concentrations of HIV viremia after 6 cycles of pembrolizumab did not demonstrate clonal expansion of HIV-infected cells. These data are consistent with anti\u2013PD-1 being able to reverse HIV latency in vivo and support the rationale for combining anti\u2013PD-1 with other interventions to reduce the HIV reservoir.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.abl3836","type":"journal-article","created":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T18:53:20Z","timestamp":1643223200000},"source":"Crossref","is-referenced-by-count":104,"title":["Pembrolizumab induces HIV latency reversal in people living with HIV and cancer on antiretroviral therapy"],"prefix":"10.1126","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6959-0924","authenticated-orcid":true,"given":"Thomas S.","family":"Uldrick","sequence":"first","affiliation":[{"name":"Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA."},{"name":"University of Washington, Seattle, WA 98109, USA."},{"name":"HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8411-8051","authenticated-orcid":true,"given":"Scott V.","family":"Adams","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8153-1799","authenticated-orcid":true,"given":"Remi","family":"Fromentin","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Infectiology, and Immunology, Universit\u00e9 de Montr\u00e9al and Centre de Recherche du CHUM, Montr\u00e9al H2X0A9, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8819-0096","authenticated-orcid":true,"given":"Michael","family":"Roche","sequence":"additional","affiliation":[{"name":"RMIT University, Melbourne, VIC 3083, Australia."},{"name":"Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6263-0153","authenticated-orcid":true,"given":"Steven P.","family":"Fling","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscila H.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5794-7292","authenticated-orcid":true,"given":"Kathryn","family":"Lurain","sequence":"additional","affiliation":[{"name":"HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5709-4675","authenticated-orcid":true,"given":"Ramya","family":"Ramaswami","sequence":"additional","affiliation":[{"name":"HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-ching Jackie","family":"Wang","sequence":"additional","affiliation":[{"name":"University of California, San Francisco, San Francisco, CA 94110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1773-9085","authenticated-orcid":true,"given":"Robert J.","family":"Gorelick","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorden L.","family":"Welker","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6296-2788","authenticated-orcid":true,"given":"Liz","family":"O\u2019Donoghue","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0010-7556","authenticated-orcid":true,"given":"Harleen","family":"Choudhary","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9494-0268","authenticated-orcid":true,"given":"Jeffrey D.","family":"Lifson","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5354-2442","authenticated-orcid":true,"given":"Thomas A.","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia."},{"name":"Department of Infectious Diseases, Aarhus University Hospital, Aarhus 8200, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajantha","family":"Rhodes","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4851-652X","authenticated-orcid":true,"given":"Carolin","family":"Tumpach","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3057-1395","authenticated-orcid":true,"given":"Robert","family":"Yarchoan","sequence":"additional","affiliation":[{"name":"HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3062-5250","authenticated-orcid":true,"given":"Frank","family":"Maldarelli","sequence":"additional","affiliation":[{"name":"HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6892-4141","authenticated-orcid":true,"given":"Martin A.","family":"Cheever","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7816-4828","authenticated-orcid":true,"given":"Rafick","family":"S\u00e9kaly","sequence":"additional","affiliation":[{"name":"Emory University, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9747-5018","authenticated-orcid":true,"given":"Nicolas","family":"Chomont","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Infectiology, and Immunology, Universit\u00e9 de Montr\u00e9al and Centre de Recherche du CHUM, Montr\u00e9al H2X0A9, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6371-747X","authenticated-orcid":true,"given":"Steven G.","family":"Deeks","sequence":"additional","affiliation":[{"name":"University of California, San Francisco, San Francisco, CA 94110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0330-8241","authenticated-orcid":true,"given":"Sharon R.","family":"Lewin","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia."},{"name":"Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia."},{"name":"Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, VIC 3004, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(20)30232-0"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI145254"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2019.03.004"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf6517"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1027-4"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11904-020-00525-y"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000000314"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005761"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4113"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08798-7"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007619"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000001849"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1901191"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx696"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1530"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy259"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0306-5"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1972"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2019.2244"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI138099"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2017.06.002"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003338"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0063818"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020006372"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-1022-1"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01590-5"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2019.0393"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(20)30234-4"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.06.028"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000002716"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-020-00143-y"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0116306"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004473"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103241"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2015.06.019"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01736-19"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.2144\/000113370"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2055-6640(20)30047-9"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2009.06.008"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.abl3836","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T17:46:34Z","timestamp":1705427194000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.abl3836"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,26]]},"references-count":39,"journal-issue":{"issue":"629","published-print":{"date-parts":[[2022,1,26]]}},"alternative-id":["10.1126\/scitranslmed.abl3836"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.abl3836","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,26]]},"article-number":"eabl3836"}}