{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T01:28:58Z","timestamp":1794360538997,"version":"4.9.0"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"8100","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":51,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2026,2,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The identification of therapeutic strategies to induce sustained antiretroviral therapy (ART)-free control of HIV infection is a major priority\n                    <jats:sup>1<\/jats:sup>\n                    . Combination immunotherapy including HIV vaccination, immune stimulation,\u00a0latency reversal and passive transfer of broadly neutralizing antibodies (bNAbs) has shown promise in non-human primate models\n                    <jats:sup>2\u20136<\/jats:sup>\n                    , but few studies have translated such approaches into people. Here we performed a single-arm, proof-of-concept study in ten people living\u00a0with HIV on ART, combining the following three approaches: (1) therapeutic vaccination with an HIV\u00a0Gag conserved\u00a0element-targeted DNA\u2009+\u2009IL-12 prime\/modified vaccinia Ankara (MVA) boost regimen followed by (2) administration of two bNAbs (10-1074, VRC07-523LS) and a toll-like receptor 9 agonist (lefitolimod) during ART suppression, followed by (3) repeat bNAb administration at the time of ART interruption (Clinicaltrials.gov:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04357821\" ext-link-type=\"uri\">NCT04357821<\/jats:ext-link>\n                    ). Seven out of the ten participants exhibited post-intervention control after pausing\u00a0ART, independent of residual bNAb plasma levels. Robust expansion of activated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells early in response to rebounding virus correlated with a lower median viral load after peak viraemia off ART. These data suggest that combination immunotherapy approaches might prove effective in inducing sustained control of HIV by slowing rebound and improving CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses, and that these approaches should continue to be optimized.\n                  <\/jats:p>","DOI":"10.1038\/s41586-025-09929-5","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T16:02:09Z","timestamp":1764604929000},"page":"187-195","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Correlates of HIV-1 control after combination immunotherapy"],"prefix":"10.1038","volume":"650","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0585-6230","authenticated-orcid":false,"given":"M. J.","family":"Peluso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4095-2036","authenticated-orcid":false,"given":"D. A.","family":"Sandel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4722-463X","authenticated-orcid":false,"given":"A. N.","family":"Deitchman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. J.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9132-0496","authenticated-orcid":false,"given":"T.","family":"Dalhuisen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9493-3497","authenticated-orcid":false,"given":"H. P.","family":"Tummala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Tib\u00farcio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Zemelko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. M.","family":"Borgo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. S.","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Deswal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. C.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Hoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6627-4624","authenticated-orcid":false,"given":"M.","family":"Shimoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Narpala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Serebryannyy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9178-9139","authenticated-orcid":false,"given":"M.","family":"Khalili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5595-1773","authenticated-orcid":false,"given":"E.","family":"Vendrame","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"SenGupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8721-8701","authenticated-orcid":false,"given":"L. S.","family":"Whitmore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1381-265X","authenticated-orcid":false,"given":"J.","family":"Tisoncik-Go","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6332-7436","authenticated-orcid":false,"suffix":"Jr","given":"M.","family":"Gale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. A.","family":"Koup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4461-8158","authenticated-orcid":false,"given":"J. I.","family":"Mullins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8925-8128","authenticated-orcid":false,"given":"B. K.","family":"Felber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. N.","family":"Pavlakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. D.","family":"Reeves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5496-8090","authenticated-orcid":false,"given":"C. J.","family":"Petropoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. V.","family":"Glidden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5291-3819","authenticated-orcid":false,"given":"M. H.","family":"Spitzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Gama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1727-8693","authenticated-orcid":false,"given":"M.","family":"Caskey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0592-8564","authenticated-orcid":false,"given":"M. C.","family":"Nussenzweig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4865-4348","authenticated-orcid":false,"given":"K. W.","family":"Chew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6684-0622","authenticated-orcid":false,"given":"T. J.","family":"Henrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. A.","family":"Yukl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. B.","family":"Cohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6371-747X","authenticated-orcid":false,"given":"S. G.","family":"Deeks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. L.","family":"Rutishauser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"9929_CR1","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1038\/s41579-023-00914-1","volume":"21","author":"RJ Landovitz","year":"2023","unstructured":"Landovitz, R. J., Scott, H. & Deeks, S. G. Prevention, treatment and cure of HIV infection. Nat. Rev. Microbiol. 21, 657\u2013670 (2023).","journal-title":"Nat. Rev. Microbiol."},{"key":"9929_CR2","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/nature21435","volume":"543","author":"Y Nishimura","year":"2017","unstructured":"Nishimura, Y. et al. Early antibody therapy can induce long-lasting immunity to SHIV. Nature 543, 559\u2013563 (2017).","journal-title":"Nature"},{"key":"9929_CR3","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1038\/nature20583","volume":"540","author":"EN Borducchi","year":"2016","unstructured":"Borducchi, E. N. et al. Ad26\/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys. Nature 540, 284\u2013287 (2016).","journal-title":"Nature"},{"key":"9929_CR4","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1038\/s41586-018-0600-6","volume":"563","author":"EN Borducchi","year":"2018","unstructured":"Borducchi, E. N. et al. Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys. Nature 563, 360\u2013364 (2018).","journal-title":"Nature"},{"key":"9929_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31196-5","volume":"13","author":"VEK Walker-Sperling","year":"2022","unstructured":"Walker-Sperling, V. E. K. et al. Therapeutic efficacy of combined active and passive immunization in ART-suppressed, SHIV-infected rhesus macaques. Nat. Commun. 13, 3463 (2022).","journal-title":"Nat. Commun."},{"key":"9929_CR6","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1126\/science.adf7966","volume":"383","author":"S-Y Lim","year":"2024","unstructured":"Lim, S.-Y. et al. Induction of durable remission by dual immunotherapy in SHIV-infected ART-suppressed macaques. Science 383, 1104\u20131111 (2024).","journal-title":"Science"},{"key":"9929_CR7","doi-asserted-by":"crossref","unstructured":"Sandel, D. A., Rutishauser, R. L. & Peluso, M. J. Post-intervention control in HIV immunotherapy trials. Curr. Opin. HIV AIDS 20, 70\u201379 (2024).","DOI":"10.1097\/COH.0000000000000890"},{"key":"9929_CR8","doi-asserted-by":"publisher","first-page":"eaan8848","DOI":"10.1126\/scitranslmed.aan8848","volume":"9","author":"MC Sneller","year":"2017","unstructured":"Sneller, M. C. et al. A randomized controlled safety\/efficacy trial of therapeutic vaccination in HIV-infected individuals who initiated antiretroviral therapy early in infection. Sci. Transl. Med. 9, eaan8848 (2017).","journal-title":"Sci. Transl. Med."},{"key":"9929_CR9","doi-asserted-by":"publisher","first-page":"2611","DOI":"10.1038\/s41591-022-02060-2","volume":"28","author":"L Bail\u00f3n","year":"2022","unstructured":"Bail\u00f3n, L. et al. Safety, immunogenicity and effect on viral rebound of HTI vaccines in early treated HIV-1 infection: a randomized, placebo-controlled phase 1 trial. Nat. Med. 28, 2611\u20132621 (2022).","journal-title":"Nat. Med."},{"key":"9929_CR10","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1038\/s41586-022-04597-1","volume":"606","author":"C Gaebler","year":"2022","unstructured":"Gaebler, C. et al. Prolonged viral suppression with anti-HIV-1 antibody therapy. Nature 606, 368\u2013374 (2022).","journal-title":"Nature"},{"key":"9929_CR11","doi-asserted-by":"publisher","first-page":"2547","DOI":"10.1038\/s41591-023-02547-6","volume":"29","author":"JD Gunst","year":"2023","unstructured":"Gunst, J. D. et al. Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence: the randomized phase 2a TITAN trial. Nat. Med. 29, 2547\u20132558 (2023).","journal-title":"Nat. Med."},{"key":"9929_CR12","doi-asserted-by":"publisher","first-page":"3534","DOI":"10.1038\/s41591-024-03247-5","volume":"30","author":"B Julg","year":"2024","unstructured":"Julg, B. et al. Safety and antiviral effect of a triple combination of HIV-1 broadly neutralizing antibodies: a phase 1\/2a trial. Nat. Med. 30, 3534\u20133543 (2024).","journal-title":"Nat. Med."},{"key":"9929_CR13","doi-asserted-by":"publisher","first-page":"2424","DOI":"10.1038\/s41591-022-02023-7","volume":"28","author":"JD Gunst","year":"2022","unstructured":"Gunst, J. D. et al. Early intervention with 3BNC117 and romidepsin at antiretroviral treatment initiation in people with HIV-1: a phase 1b\/2a, randomized trial. Nat. Med. 28, 2424\u20132435 (2022).","journal-title":"Nat. Med."},{"key":"9929_CR14","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1038\/s41591-019-0747-1","volume":"26","author":"J Niessl","year":"2020","unstructured":"Niessl, J. et al. Combination anti-HIV-1 antibody therapy is associated with increased virus-specific T cell immunity. Nat. Med. 26, 222\u2013227 (2020).","journal-title":"Nat. Med."},{"key":"9929_CR15","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1038\/nm.2233","volume":"16","author":"CT Ng","year":"2010","unstructured":"Ng, C. T. et al. Passive neutralizing antibody controls SHIV viremia and enhances B cell responses in infant macaques. Nat. Med. 16, 1117\u20131119 (2010).","journal-title":"Nat. Med."},{"key":"9929_CR16","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1016\/j.cell.2015.04.016","volume":"161","author":"DJ DiLillo","year":"2015","unstructured":"DiLillo, D. J. & Ravetch, J. V. Differential fc-receptor engagement drives an anti-tumor vaccinal effect. Cell 161, 1035\u20131045 (2015).","journal-title":"Cell"},{"key":"9929_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34171-2","volume":"13","author":"M Ros\u00e1s-Umbert","year":"2022","unstructured":"Ros\u00e1s-Umbert, M. et al. Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8+ T cell immunity. Nat. Commun. 13, 6473 (2022).","journal-title":"Nat. Commun."},{"key":"9929_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-56116-1","volume":"16","author":"JD Gunst","year":"2025","unstructured":"Gunst, J. D. et al. Time to HIV viral rebound and frequency of post-treatment control after analytical interruption of antiretroviral therapy: an individual data-based meta-analysis of 24 prospective studies. Nat. Commun. 16, 906 (2025).","journal-title":"Nat. Commun."},{"key":"9929_CR19","doi-asserted-by":"publisher","first-page":"3999","DOI":"10.4049\/jimmunol.1600697","volume":"197","author":"X Hu","year":"2016","unstructured":"Hu, X. et al. DNA prime-boost vaccine regimen to increase breadth, magnitude, and cytotoxicity of the cellular immune responses to subdominant gag epitopes of simian immunodeficiency virus and HIV. J. Immunol. 197, 3999\u20134013 (2016).","journal-title":"J. Immunol."},{"key":"9929_CR20","doi-asserted-by":"publisher","first-page":"e667","DOI":"10.1016\/S2352-3018(19)30181-X","volume":"6","author":"MR Gaudinski","year":"2019","unstructured":"Gaudinski, M. R. et al. Safety and pharmacokinetics of broadly neutralising human monoclonal antibody VRC07-523LS in healthy adults: a phase 1 dose-escalation clinical trial. Lancet HIV 6, e667\u2013e679 (2019).","journal-title":"Lancet HIV"},{"key":"9929_CR21","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1093\/cid\/cix201","volume":"64","author":"L Vibholm","year":"2017","unstructured":"Vibholm, L. et al. Short-course Toll-like receptor 9 agonist treatment impacts innate immunity and plasma viremia in individuals with human immunodeficiency virus infection. Clin. Infect. Dis. 64, 1686\u20131695 (2017).","journal-title":"Clin. Infect. Dis."},{"key":"9929_CR22","doi-asserted-by":"publisher","first-page":"1954","DOI":"10.1093\/infdis\/jiy479","volume":"218","author":"G Namazi","year":"2018","unstructured":"Namazi, G. et al. The control of HIV after antiretroviral medication pause (CHAMP) study: posttreatment controllers identified from 14 clinical studies. J. Infect. Dis. 218, 1954\u20131963 (2018).","journal-title":"J. Infect. Dis."},{"key":"9929_CR23","doi-asserted-by":"publisher","first-page":"e2218960120","DOI":"10.1073\/pnas.2218960120","volume":"120","author":"B Etemad","year":"2023","unstructured":"Etemad, B. et al. HIV post-treatment controllers have distinct immunological and virological features. Proc. Natl Acad. Sci. USA 120, e2218960120 (2023).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"9929_CR24","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1038\/s41586-019-0898-8","volume":"566","author":"KM Bruner","year":"2019","unstructured":"Bruner, K. M. et al. A quantitative approach for measuring the reservoir of latent HIV-1 proviruses. Nature 566, 120\u2013125 (2019).","journal-title":"Nature"},{"key":"9929_CR25","doi-asserted-by":"publisher","first-page":"e1002417","DOI":"10.1371\/journal.pmed.1002417","volume":"14","author":"TJ Henrich","year":"2017","unstructured":"Henrich, T. J. et al. HIV-1 persistence following extremely early initiation of antiretroviral therapy (ART) during acute HIV-1 infection: an observational study. PLoS Med. 14, e1002417 (2017).","journal-title":"PLoS Med."},{"key":"9929_CR26","doi-asserted-by":"publisher","first-page":"e136648","DOI":"10.1172\/jci.insight.136648","volume":"6","author":"RL Rutishauser","year":"2021","unstructured":"Rutishauser, R. L. et al. TCF-1 regulates HIV-specific CD8+ T cell expansion capacity. JCI Insight 6, e136648 (2021).","journal-title":"JCI Insight"},{"key":"9929_CR27","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1038\/ni845","volume":"3","author":"SA Migueles","year":"2002","unstructured":"Migueles, S. A. et al. HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors. Nat. Immunol. 3, 1061\u20131068 (2002).","journal-title":"Nat. Immunol."},{"key":"9929_CR28","doi-asserted-by":"publisher","first-page":"10735","DOI":"10.1128\/JVI.01527-15","volume":"89","author":"ZM Ndhlovu","year":"2015","unstructured":"Ndhlovu, Z. M. et al. The breadth of expandable memory CD8+ T cells inversely correlates with residual viral loads in HIV elite controllers. J. Virol. 89, 10735\u201310747 (2015).","journal-title":"J. Virol."},{"key":"9929_CR29","doi-asserted-by":"publisher","first-page":"2372","DOI":"10.1016\/j.immuni.2021.08.007","volume":"54","author":"DR Collins","year":"2021","unstructured":"Collins, D. R. et al. Functional impairment of HIV-specific CD8+ T cells precedes aborted spontaneous control of viremia. Immunity 54, 2372\u20132384 (2021).","journal-title":"Immunity"},{"key":"9929_CR30","doi-asserted-by":"publisher","first-page":"e1003211","DOI":"10.1371\/journal.ppat.1003211","volume":"9","author":"A S\u00e1ez-Ciri\u00f3n","year":"2013","unstructured":"S\u00e1ez-Ciri\u00f3n, A. et al. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study. PLoS Pathog. 9, e1003211 (2013).","journal-title":"PLoS Pathog."},{"key":"9929_CR31","doi-asserted-by":"publisher","first-page":"100670","DOI":"10.1016\/j.medj.2025.100670","volume":"6","author":"A Essat","year":"2025","unstructured":"Essat, A. et al. A genetic fingerprint associated with durable HIV remission after interruption of antiretroviral treatment: ANRS VISCONTI\/PRIMO. Med 6, 100670 (2025).","journal-title":"Med"},{"key":"9929_CR32","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1038\/s41591-018-0026-6","volume":"24","author":"DJ Colby","year":"2018","unstructured":"Colby, D. J. et al. Rapid HIV RNA rebound after antiretroviral treatment interruption in persons durably suppressed in Fiebig I acute HIV infection. Nat. Med. 24, 923\u2013926 (2018).","journal-title":"Nat. Med."},{"key":"9929_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-44389-3","volume":"15","author":"C Passaes","year":"2024","unstructured":"Passaes, C. et al. Early antiretroviral therapy favors post-treatment SIV control associated with the expansion of enhanced memory CD8+ T-cells. Nat. Commun. 15, 178 (2024).","journal-title":"Nat. Commun."},{"key":"9929_CR34","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/S1074-7613(00)80470-7","volume":"8","author":"K Murali-Krishna","year":"1998","unstructured":"Murali-Krishna, K. et al. Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. Immunity 8, 177\u2013187 (1998).","journal-title":"Immunity"},{"key":"9929_CR35","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1016\/j.immuni.2015.08.012","volume":"43","author":"ZM Ndhlovu","year":"2015","unstructured":"Ndhlovu, Z. M. et al. Magnitude and kinetics of CD8+ T cell activation during hyperacute HIV infection impact viral set point. Immunity 43, 591\u2013604 (2015).","journal-title":"Immunity"},{"key":"9929_CR36","doi-asserted-by":"publisher","first-page":"eaag1809","DOI":"10.1126\/scitranslmed.aag1809","volume":"9","author":"H Takata","year":"2017","unstructured":"Takata, H. et al. Delayed differentiation of potent effector CD8+ T cells reducing viremia and reservoir seeding in acute HIV infection. Sci. Transl. Med. 9, eaag1809 (2017).","journal-title":"Sci. Transl. Med."},{"key":"9929_CR37","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.immuni.2016.07.021","volume":"45","author":"DT Utzschneider","year":"2016","unstructured":"Utzschneider, D. T. et al. T cell factor 1-expressing memory-like CD8+ T cells sustain the immune response to chronic viral infections. Immunity 45, 415\u2013427 (2016).","journal-title":"Immunity"},{"key":"9929_CR38","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/j.immuni.2020.04.014","volume":"52","author":"J-C Beltra","year":"2020","unstructured":"Beltra, J.-C. et al. Developmental relationships of four exhausted CD8+ T cell subsets reveals underlying transcriptional and epigenetic landscape control mechanisms. Immunity 52, 825\u2013841 (2020).","journal-title":"Immunity"},{"key":"9929_CR39","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1016\/j.immuni.2023.02.017","volume":"56","author":"M Koutsakos","year":"2023","unstructured":"Koutsakos, M. et al. SARS-CoV-2 breakthrough infection induces rapid memory and de novo T cell responses. Immunity 56, 879\u2013892 (2023).","journal-title":"Immunity"},{"key":"9929_CR40","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1038\/nature22079","volume":"545","author":"AC Huang","year":"2017","unstructured":"Huang, A. C. et al. T-cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature 545, 60\u201365 (2017).","journal-title":"Nature"},{"key":"9929_CR41","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/s41590-019-0312-6","volume":"20","author":"BC Miller","year":"2019","unstructured":"Miller, B. C. et al. Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade. Nat. Immunol. 20, 326\u2013336 (2019).","journal-title":"Nat. Immunol."},{"key":"9929_CR42","doi-asserted-by":"publisher","first-page":"e192731","DOI":"10.1172\/JCI192731","volume":"135","author":"SL Reiner","year":"2025","unstructured":"Reiner, S. L. Immune regeneration: implications for cancer immunotherapy and beyond. J. Clin. Invest. 135, e192731 (2025).","journal-title":"J. Clin. Invest."},{"key":"9929_CR43","doi-asserted-by":"publisher","first-page":"104253","DOI":"10.1016\/j.ebiom.2022.104253","volume":"84","author":"H Takata","year":"2022","unstructured":"Takata, H. et al. Long-term antiretroviral therapy initiated in acute HIV infection prevents residual dysfunction of HIV-specific CD8+ T cells. EBioMedicine 84, 104253 (2022).","journal-title":"EBioMedicine"},{"key":"9929_CR44","doi-asserted-by":"publisher","first-page":"eaau0528","DOI":"10.1126\/scitranslmed.aau0528","volume":"11","author":"ZM Ndhlovu","year":"2019","unstructured":"Ndhlovu, Z. M. et al. Augmentation of HIV-specific T cell function by immediate treatment of hyperacute HIV-1 infection. Sci. Transl. Med. 11, eaau0528 (2019).","journal-title":"Sci. Transl. Med."},{"key":"9929_CR45","doi-asserted-by":"publisher","first-page":"10056","DOI":"10.1128\/JVI.01046-14","volume":"88","author":"MJ Buzon","year":"2014","unstructured":"Buzon, M. J. et al. Long-term antiretroviral treatment initiated at primary HIV-1 infection affects the size, composition, and decay kinetics of the reservoir of HIV-1-infected CD4 T cells. J. Virol. 88, 10056\u201310065 (2014).","journal-title":"J. Virol."},{"key":"9929_CR46","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.ebiom.2016.07.024","volume":"11","author":"J Ananworanich","year":"2016","unstructured":"Ananworanich, J. et al. HIV DNA set point is rapidly established in acute HIV infection and dramatically reduced by early ART. EBioMedicine 11, 68\u201372 (2016).","journal-title":"EBioMedicine"},{"key":"9929_CR47","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.1056\/NEJM200105313442203","volume":"344","author":"X Gao","year":"2001","unstructured":"Gao, X. et al. Effect of a single amino acid change in MHC class I molecules on the rate of progression to AIDS. N. Engl. J. Med. 344, 1668\u20131675 (2001).","journal-title":"N. Engl. J. Med."},{"key":"9929_CR48","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1126\/science.1143767","volume":"317","author":"J Fellay","year":"2007","unstructured":"Fellay, J. et al. A whole-genome association study of major determinants for host control of HIV-1. Science 317, 944\u2013947 (2007).","journal-title":"Science"},{"key":"9929_CR49","doi-asserted-by":"publisher","first-page":"461","DOI":"10.7326\/M14-1084","volume":"161","author":"JL Lennox","year":"2014","unstructured":"Lennox, J. L. et al. Efficacy and tolerability of 3 nonnucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens for treatment-naive volunteers infected with HIV-1: a randomized, controlled equivalence trial. Ann. Intern. Med. 161, 461\u2013471 (2014).","journal-title":"Ann. Intern. Med."},{"key":"9929_CR50","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/S2055-6640(20)30009-1","volume":"6","author":"MJ Peluso","year":"2020","unstructured":"Peluso, M. J. et al. A collaborative, multidisciplinary approach to HIV transmission risk mitigation during analytic treatment interruption. J. Virus Erad. 6, 34\u201337 (2020).","journal-title":"J. Virus Erad."},{"key":"9929_CR51","doi-asserted-by":"publisher","first-page":"2312318","DOI":"10.1080\/25787489.2024.2312318","volume":"25","author":"K Dub\u00e9","year":"2024","unstructured":"Dub\u00e9, K. et al. Participant experiences in a combination HIV cure-related trial with extended analytical treatment interruption in San Francisco, United States. HIV Res. Clin. Pract. 25, 2312318 (2024).","journal-title":"HIV Res. Clin. Pract."},{"key":"9929_CR52","doi-asserted-by":"publisher","first-page":"4136","DOI":"10.1007\/s10461-024-04485-x","volume":"28","author":"A Korolkova","year":"2024","unstructured":"Korolkova, A. et al. Recall and appraisal of the risks, benefits, and objectives of interrupting HIV treatment in an HIV cure-related study. AIDS Behav. 28, 4136\u20134145 (2024).","journal-title":"AIDS Behav."},{"key":"9929_CR53","doi-asserted-by":"publisher","first-page":"1843","DOI":"10.1093\/cid\/ciaa1260","volume":"72","author":"MJ Peluso","year":"2021","unstructured":"Peluso, M. J. et al. Operationalizing human immunodeficiency virus cure-related trials with analytic treatment interruptions during the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) pandemic: a collaborative approach. Clin. Infect. Dis. 72, 1843\u20131849 (2021).","journal-title":"Clin. Infect. Dis."},{"key":"9929_CR54","doi-asserted-by":"publisher","first-page":"e232","DOI":"10.1097\/QAI.0000000000002690","volume":"87","author":"MJ Peluso","year":"2021","unstructured":"Peluso, M. J. et al. SARS-CoV-2 vaccination in the context of ongoing HIV cure-related research studies. J. Acquir. Immune Defic. Syndr. 87, e232\u2013e233 (2021).","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"9929_CR55","doi-asserted-by":"publisher","first-page":"e30","DOI":"10.1097\/QAI.0000000000002875","volume":"89","author":"MJ Peluso","year":"2022","unstructured":"Peluso, M. J. et al. SARS-CoV-2 booster vaccination for participants in \u2018HIV cure\u2019-related clinical trials. J. Acquir. Immune Defic. Syndr. 89, e30 (2022).","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"9929_CR56","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1097\/QAI.0000000000002502","volume":"85","author":"D Gingrich","year":"2020","unstructured":"Gingrich, D. et al. Methotrexate decreases tenofovir exposure in antiretroviral-suppressed individuals living with HIV. J. Acquir. Immune Defic. Syndr. 85, 651\u2013658 (2020).","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"9929_CR57","doi-asserted-by":"publisher","first-page":"e230","DOI":"10.1016\/S2352-3018(23)00003-6","volume":"10","author":"S Mahomed","year":"2023","unstructured":"Mahomed, S. et al. Safety and pharmacokinetics of escalating doses of neutralising monoclonal antibody CAP256V2LS administered with and without VRC07-523LS in HIV-negative women in South Africa (CAPRISA 012B): a phase 1, dose-escalation, randomised controlled trial. Lancet HIV 10, e230\u2013e243 (2023).","journal-title":"Lancet HIV"},{"key":"9929_CR58","doi-asserted-by":"publisher","first-page":"194","DOI":"10.2144\/000114159","volume":"56","author":"SA Yukl","year":"2014","unstructured":"Yukl, S. A., Kaiser, P., Kim, P., Li, P. & Wong, J. K. Advantages of using the QIAshredder instead of restriction digestion to prepare DNA for droplet digital PCR. Biotechniques 56, 194\u2013196 (2014).","journal-title":"Biotechniques"},{"key":"9929_CR59","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1097\/QAD.0000000000003908","volume":"38","author":"GN Kadiyala","year":"2024","unstructured":"Kadiyala, G. N. et al. Differential susceptibility of cells infected with defective and intact HIV proviruses to killing by obatoclax and other small molecules. AIDS 38, 1281\u20131291 (2024).","journal-title":"AIDS"},{"key":"9929_CR60","doi-asserted-by":"publisher","first-page":"eaap9927","DOI":"10.1126\/scitranslmed.aap9927","volume":"10","author":"SA Yukl","year":"2018","unstructured":"Yukl, S. A. et al. HIV latency in isolated patient CD4 + T cells may be due to blocks in HIV transcriptional elongation, completion, and splicing. Sci. Transl. Med. 10, eaap9927 (2018).","journal-title":"Sci. Transl. Med."},{"key":"9929_CR61","doi-asserted-by":"publisher","first-page":"110815","DOI":"10.1016\/j.celrep.2022.110815","volume":"39","author":"EE McCarthy","year":"2022","unstructured":"McCarthy, E. E. et al. A cytotoxic-skewed immune set point predicts low neutralizing antibody levels after Zika virus infection. Cell Rep. 39, 110815 (2022).","journal-title":"Cell Rep."},{"key":"9929_CR62","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.cell.2016.12.022","volume":"168","author":"MH Spitzer","year":"2017","unstructured":"Spitzer, M. H. et al. Systemic immunity is required for effective cancer immunotherapy. Cell 168, 487\u2013502 (2017).","journal-title":"Cell"},{"key":"9929_CR63","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","volume":"9","author":"B Langmead","year":"2012","unstructured":"Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357\u2013359 (2012).","journal-title":"Nat. Methods"},{"key":"9929_CR64","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15\u201321 (2013).","journal-title":"Bioinformatics"},{"key":"9929_CR65","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2010-11-3-r25","volume":"11","author":"MD Robinson","year":"2010","unstructured":"Robinson, M. D. & Oshlack, A. A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol. 11, R25 (2010).","journal-title":"Genome Biol."},{"key":"9929_CR66","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2014-15-2-r29","volume":"15","author":"CW Law","year":"2014","unstructured":"Law, C. W., Chen, Y., Shi, W. & Smyth, G. K. voom: precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol. 15, R29 (2014).","journal-title":"Genome Biol."},{"key":"9929_CR67","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).","journal-title":"Nucleic Acids Res."}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41586-025-09929-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-025-09929-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-025-09929-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T08:03:23Z","timestamp":1770278603000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41586-025-09929-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,1]]},"references-count":67,"journal-issue":{"issue":"8100","published-print":{"date-parts":[[2026,2,5]]}},"alternative-id":["9929"],"URL":"https:\/\/doi.org\/10.1038\/s41586-025-09929-5","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-6141479\/v1","asserted-by":"object"}]},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,1]]},"assertion":[{"value":"2 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"M.J.P. serves on a DSMB for American Gene Technologies. S.G.D. reports consulting fees from AbbVie, GSK, Hookipa, American Gene Technologies and Immunocore; owns Tendel stock; and receives research support from Gilead. M.H.S. is founder and shareholder of Pro Biosciences and Teiko.bio; has been a paid consultant for Five Prime, Ono, January, Earli, Astellas and Indaptus Therapeutics; and reports research funding from Roche\/Genentech, Pfizer, Valitor and Bristol Myers Squibb. M.C. served on a Gilead scientific advisory board. M.C.N. has a patent to the bNAbs 10-1074 and 3BNC117 issued (Gilead); is on the scientific advisory board of Celldex and reports personal fees from Gilead and Frontier Biosciences. B.K.F., G.N.P. and J.I.M. are listed as inventors on US-Government-owned patents related to the CE DNA vaccine. M.K. has received funding to her institution from Gilead Sciences and Intercept Pharmaceuticals and serves as a scientific consultant for Gilead Sciences, GSK pharmaceuticals and Resolution Therapeutics. J.D.R. and C.J.P. are employees of Labcorp-Monogram Biosciences and shareholders of Labcorp. D.S. and E.V. are employees of and hold stock in Gilead Sciences.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}