{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T20:30:01Z","timestamp":1793997001375,"version":"4.8.0"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":38,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Precise and scalable quantification of the intact HIV reservoir is critical for advancing curative strategies. Current reservoir assays, such as the intact proviral DNA assay (IPDA), are limited by quantification failures or misclassification of defective proviruses due to HIV sequence heterogeneity. Q4ddPCR is a modular, droplet digital PCR simultaneously targeting four conserved regions in the HIV genome to improve specificity, reduce quantification gaps, and provide multi-layered readouts. It comprises two configurations: one fully based on Q4PCR primer\/probes and one combining IPDA with\n                    <jats:italic>gag<\/jats:italic>\n                    and\n                    <jats:italic>pol<\/jats:italic>\n                    primer\/probes from Q4PCR. We benchmark Q4ddPCR against 3650 near full-length proviral sequences from 13 virally suppressed people with HIV (PWH) generated by Q4PCR. Q4ddPCR closely matches sequence-confirmed reservoir measurements, and multi-probe readouts reveal clonal reservoir dynamics not detectable by IPDA. Q4ddPCR enables intact reservoir quantification in 95% of samples across four independent cohorts and in 16 PWH, strongly correlates with viral outgrowth. In longitudinal samples from 42 participants over the first 4.5 years on antiretroviral therapy (ART), Q4ddPCR reports lower proviral frequencies and a steeper decline in intact proviral DNA compared to IPDA. Collectively, our findings confirm key predictions from mathematical modeling, demonstrating that multi-target assays improve specificity and more accurately capture intact reservoir dynamics.\n                  <\/jats:p>","DOI":"10.1038\/s41467-026-69413-0","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T14:47:37Z","timestamp":1771598857000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Q4ddPCR: a flexible, 4-target assay for high-resolution HIV reservoir profiling"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8354-9943","authenticated-orcid":false,"given":"Rachel","family":"Scheck","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3573-0531","authenticated-orcid":false,"given":"Mark","family":"Melzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0206-6575","authenticated-orcid":false,"given":"Gregory","family":"Gladkov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Leyre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7038-5597","authenticated-orcid":false,"given":"Adam R.","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5684-9538","authenticated-orcid":false,"given":"Daniel B.","family":"Reeves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Perkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0286-3946","authenticated-orcid":false,"given":"T. Thinh","family":"Huynh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah K.","family":"McMahon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald J.","family":"Bosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0405-0991","authenticated-orcid":false,"given":"Bernard J.","family":"Macatangay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3601-4837","authenticated-orcid":false,"given":"Joshua C.","family":"Cyktor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4938-0644","authenticated-orcid":false,"given":"Joseph J.","family":"Eron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Mellors","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh T.","family":"Gandhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4722-8390","authenticated-orcid":false,"given":"Lisa","family":"Buchauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4470-1231","authenticated-orcid":false,"given":"R. Brad","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7295-8128","authenticated-orcid":false,"given":"Christian","family":"Gaebler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"69413_CR1","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1038\/s41591-021-01590-5","volume":"27","author":"SG Deeks","year":"2021","unstructured":"Deeks, S. G. et al. Research priorities for an HIV cure: International AIDS Society Global Scientific Strategy 2021. Nat. Med. 27, 2085\u20132098 (2021).","journal-title":"Nat. Med."},{"key":"69413_CR2","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1126\/science.278.5341.1291","volume":"278","author":"JK Wong","year":"1997","unstructured":"Wong, J. K. et al. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science 278, 1291\u20131295 (1997).","journal-title":"Science"},{"key":"69413_CR3","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1016\/j.cell.2013.09.020","volume":"155","author":"Y-C Ho","year":"2013","unstructured":"Ho, Y.-C. et al. Replication-Competent Noninduced Proviruses in the Latent Reservoir Increase Barrier to HIV-1 Cure. Cell 155, 540\u2013551 (2013).","journal-title":"Cell"},{"key":"69413_CR4","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1038\/s41591-020-1022-1","volume":"26","author":"M Abdel-Mohsen","year":"2020","unstructured":"Abdel-Mohsen, M. et al. Recommendations for measuring HIV reservoir size in cure-directed clinical trials. Nat. Med. 26, 1339\u20131350 (2020).","journal-title":"Nat. Med."},{"key":"69413_CR5","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":"69413_CR6","doi-asserted-by":"crossref","unstructured":"Gaebler, C. et al. Sequence Evaluation and Comparative Analysis of Novel Assays for Intact Proviral HIV-1 DNA. J. Virol. 95, e01986\u201320 (2021).","DOI":"10.1128\/JVI.01986-20"},{"key":"69413_CR7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39837-z","volume":"14","author":"DB Reeves","year":"2023","unstructured":"Reeves, D. B. et al. Impact of misclassified defective proviruses on HIV reservoir measurements. Nat. Commun. 14, 4186 (2023).","journal-title":"Nat. Commun."},{"key":"69413_CR8","doi-asserted-by":"crossref","unstructured":"White, J. A. et al. Complex decay dynamics of HIV virions, intact and defective proviruses, and 2LTR circles following initiation of antiretroviral therapy. Proc. Natl. Acad. Sci. USA 119, e2120326119 (2022).","DOI":"10.1073\/pnas.2120326119"},{"key":"69413_CR9","doi-asserted-by":"crossref","unstructured":"McMyn, N. F. et al. The latent reservoir of inducible, infectious HIV-1 does not decrease despite decades of antiretroviral therapy. J. Clin. Invest. 133, e171554 (2023).","DOI":"10.1172\/JCI171554"},{"key":"69413_CR10","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1093\/infdis\/jiad039","volume":"227","author":"RT Gandhi","year":"2023","unstructured":"Gandhi, R. T. et al. Varied Patterns of Decay of Intact Human Immunodeficiency Virus Type 1 Proviruses Over 2 Decades of Antiretroviral Therapy. J. Infect. Dis. 227, 1376\u20131380 (2023).","journal-title":"J. Infect. Dis."},{"key":"69413_CR11","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1126\/science.278.5341.1295","volume":"278","author":"D Finzi","year":"1997","unstructured":"Finzi, D. et al. Identification of a Reservoir for HIV-1 in Patients on Highly Active Antiretroviral Therapy. Science 278, 1295\u20131300 (1997).","journal-title":"Science"},{"key":"69413_CR12","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1093\/infdis\/jiv218","volume":"212","author":"AM Crooks","year":"2015","unstructured":"Crooks, A. M. et al. Precise Quantitation of the Latent HIV-1 Reservoir: Implications for Eradication Strategies. J. Infect. Dis. 212, 1361\u20131365 (2015).","journal-title":"J. Infect. Dis."},{"key":"69413_CR13","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1093\/infdis\/jiaa532","volume":"223","author":"RT Gandhi","year":"2021","unstructured":"Gandhi, R. T. et al. Selective Decay of Intact HIV-1 Proviral DNA on Antiretroviral Therapy. J. Infect. Dis. 223, 225\u2013233 (2021).","journal-title":"J. Infect. Dis."},{"key":"69413_CR14","doi-asserted-by":"crossref","unstructured":"Peluso, M. J. et al. Differential decay of intact and defective proviral DNA in HIV-1-infected individuals on suppressive antiretroviral therapy. JCI Insight 5, e132997 (2020).","DOI":"10.1172\/jci.insight.132997"},{"key":"69413_CR15","doi-asserted-by":"publisher","first-page":"2253","DOI":"10.1084\/jem.20190896","volume":"216","author":"C Gaebler","year":"2019","unstructured":"Gaebler, C. et al. Combination of quadruplex qPCR and next-generation sequencing for qualitative and quantitative analysis of the HIV-1 latent reservoir. J. Exp. Med. 216, 2253\u20132264 (2019).","journal-title":"J. Exp. Med."},{"key":"69413_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2021.100243","volume":"2","author":"CN Levy","year":"2021","unstructured":"Levy, C. N. et al. A highly multiplexed droplet digital PCR assay to measure the intact HIV-1 proviral reservoir. Cell Rep. Med 2, 100243 (2021).","journal-title":"Cell Rep. Med"},{"key":"69413_CR17","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1093\/clinchem\/hvae192","volume":"71","author":"M Delporte","year":"2025","unstructured":"Delporte, M. et al. Integrative Assessment of Total and Intact HIV-1 Reservoir by a 5-Region Multiplexed Rainbow DNA Digital PCR Assay. Clin. Chem. 71, 203\u2013214 (2025).","journal-title":"Clin. Chem."},{"key":"69413_CR18","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.ymeth.2021.05.006","volume":"201","author":"W van Snippenberg","year":"2022","unstructured":"van Snippenberg, W. et al. Triplex digital PCR assays for the quantification of intact proviral HIV-1 DNA. Methods 201, 41\u201348 (2022).","journal-title":"Methods"},{"key":"69413_CR19","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.103615","volume":"25","author":"NAJ Cassidy","year":"2022","unstructured":"Cassidy, N. A. J. et al. HIV reservoir quantification using cross-subtype multiplex ddPCR. iScience 25, 103615 (2022).","journal-title":"iScience"},{"key":"69413_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20442-3","volume":"12","author":"NN Kinloch","year":"2021","unstructured":"Kinloch, N. N. et al. HIV-1 diversity considerations in the application of the Intact Proviral DNA Assay (IPDA). Nat. Commun. 12, 165 (2021).","journal-title":"Nat. Commun."},{"key":"69413_CR21","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s12985-024-02300-6","volume":"21","author":"NVEJ Buchholtz","year":"2024","unstructured":"Buchholtz, N. V. E. J. et al. Development of a highly sensitive and specific intact proviral DNA assay for HIV-1 subtype B and C. Virol. J. 21, 36 (2024).","journal-title":"Virol. J."},{"key":"69413_CR22","doi-asserted-by":"crossref","unstructured":"Tschumi J., Neumann K., Braun D. L., G\u00fcnthard H. F., Metzner K. J. Considerations and limitations for establishing an Intact Proviral DNA Assay (IPDA) on a chip-based digital PCR system for HIV-1 reservoir quantification. J. Virol. Methods, 115205 (2025).","DOI":"10.1016\/j.jviromet.2025.115205"},{"key":"69413_CR23","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":"69413_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-57284-w","volume":"16","author":"L Bailon","year":"2025","unstructured":"Bailon, L. et al. Safety, immunogenicity and effect on viral rebound of HTI vaccines combined with a TLR7 agonist in early-treated HIV-1 infection: a randomized, placebo-controlled phase 2a trial. Nat. Commun. 16, 2146 (2025).","journal-title":"Nat. Commun."},{"key":"69413_CR25","doi-asserted-by":"crossref","unstructured":"Cho, A. et al. Longitudinal clonal dynamics of HIV-1 latent reservoirs measured by combination quadruplex polymerase chain reaction and sequencing. Proc. Natl. Acad. Sci. USA 119, e2117630119 (2022).","DOI":"10.1073\/pnas.2117630119"},{"key":"69413_CR26","doi-asserted-by":"publisher","first-page":"e1010845","DOI":"10.1371\/journal.ppat.1010845","volume":"18","author":"JA White","year":"2022","unstructured":"White, J. A. et al. Measuring the latent reservoir for HIV-1: Quantification bias in near full-length genome sequencing methods. PLoS Pathog. 18, e1010845 (2022).","journal-title":"PLoS Pathog."},{"key":"69413_CR27","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1038\/s41586-018-0531-2","volume":"561","author":"P Mendoza","year":"2018","unstructured":"Mendoza, P. et al. Combination therapy with anti-HIV-1 antibodies maintains viral suppression. Nature 561, 479\u2013484 (2018).","journal-title":"Nature"},{"key":"69413_CR28","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":"69413_CR29","doi-asserted-by":"publisher","first-page":"e1006285","DOI":"10.1371\/journal.ppat.1006285","volume":"13","author":"RT Gandhi","year":"2017","unstructured":"Gandhi, R. T. et al. Levels of HIV-1 persistence on antiretroviral therapy are not associated with markers of inflammation or activation. PLoS Pathog. 13, e1006285 (2017).","journal-title":"PLoS Pathog."},{"key":"69413_CR30","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1093\/clinchem\/hvaa125","volume":"66","author":"JF Huggett","year":"2020","unstructured":"Huggett, J. F. The Digital MIQE Guidelines Update: Minimum Information for Publication of Quantitative Digital PCR Experiments for 2020. Clin. Chem. 66, 1012\u20131029 (2020).","journal-title":"Clin. Chem."},{"key":"69413_CR31","doi-asserted-by":"publisher","first-page":"3883","DOI":"10.1128\/JCM.40.10.3883-3884.2002","volume":"40","author":"Z Yun","year":"2002","unstructured":"Yun, Z., Fredriksson, E. & S\u00f6nnerborg, A. Quantification of human immunodeficiency virus type 1 proviral DNA by the TaqMan real-time PCR assay. J. Clin. Microbiol. 40, 3883\u20133884 (2002).","journal-title":"J. Clin. Microbiol."},{"key":"69413_CR32","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.virol.2008.05.030","volume":"379","author":"JJ Yu","year":"2008","unstructured":"Yu, J. J. et al. A more precise HIV integration assay designed to detect small differences finds lower levels of integrated DNA in HAART treated patients. Virology 379, 78\u201386 (2008).","journal-title":"Virology"},{"key":"69413_CR33","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1038\/s41586-022-05556-6","volume":"614","author":"IC Clark","year":"2023","unstructured":"Clark, I. C. et al. HIV silencing and cell survival signatures in infected T cell reservoirs. Nature 614, 318\u2013325 (2023).","journal-title":"Nature"},{"key":"69413_CR34","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/s41586-022-05538-8","volume":"614","author":"W Sun","year":"2023","unstructured":"Sun, W. et al. Phenotypic signatures of immune selection in HIV-1 reservoir cells. Nature 614, 309\u2013317 (2023).","journal-title":"Nature"},{"key":"69413_CR35","doi-asserted-by":"crossref","unstructured":"Delley C. L. et al. The Immunophenotype and proviral landscape of HIV-infected CD4 T cells during antiretroviral therapy. bioRxiv, (2025).","DOI":"10.1101\/2025.06.05.657210"},{"key":"69413_CR36","doi-asserted-by":"publisher","DOI":"10.1016\/j.jve.2021.100043","volume":"7","author":"PN Enick","year":"2021","unstructured":"Enick, P. N. et al. Comparison of methods to quantify inducible HIV-1 outgrowth. J. Virus Erad. 7, 100043 (2021).","journal-title":"J. Virus Erad."},{"key":"69413_CR37","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/S2055-6640(20)30030-3","volume":"5","author":"L Barr","year":"2019","unstructured":"Barr, L. & Jefferys, R. A landscape analysis of HIV cure-related clinical trials and observational studies in 2018. J. Virus Erad. 5, 212\u2013219 (2019).","journal-title":"J. Virus Erad."},{"key":"69413_CR38","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1080\/14787210.2023.2273919","volume":"21","author":"MD Schou","year":"2023","unstructured":"Schou, M. D., S\u00f8gaard, O. S. & Rasmussen, T. A. Clinical trials aimed at HIV cure or remission: new pathways and lessons learned. Expert Rev. Anti Infect. Ther. 21, 1227\u20131243 (2023).","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"69413_CR39","doi-asserted-by":"publisher","first-page":"2584","DOI":"10.1016\/j.immuni.2023.10.002","volume":"56","author":"Y Wei","year":"2023","unstructured":"Wei, Y. et al. Single-cell epigenetic, transcriptional, and protein profiling of latent and active HIV-1 reservoir revealed that IKZF3 promotes HIV-1 persistence. Immunity 56, 2584\u20132601.e2587 (2023).","journal-title":"Immunity"},{"key":"69413_CR40","doi-asserted-by":"publisher","first-page":"1868","DOI":"10.1093\/emboj\/cdg188","volume":"22","author":"A Jordan","year":"2003","unstructured":"Jordan, A., Bisgrove, D. & Verdin, E. HIV reproducibly establishes a latent infection after acute infection of T cells in vitro. EMBO J. 22, 1868\u20131877 (2003).","journal-title":"EMBO J."},{"key":"69413_CR41","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1089\/08892220050058344","volume":"16","author":"M Baba","year":"2000","unstructured":"Baba, M., Miyake, H., Okamoto, M., Iizawa, Y. & Okonogi, K. Establishment of a CCR5-expressing T-lymphoblastoid cell line highly susceptible to R5 HIV type 1. AIDS Res Hum. Retroviruses 16, 935\u2013941 (2000).","journal-title":"AIDS Res Hum. Retroviruses"},{"key":"69413_CR42","doi-asserted-by":"crossref","unstructured":"Rosenbloom, D. I. S. et al. Designing and interpreting limiting dilution assays: general principles and applications to the latent reservoir for human immunodeficiency Virus-1. Open Forum Infect. Dis. 2, ofv123 (2015).","DOI":"10.1093\/ofid\/ofv123"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-69413-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-69413-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-69413-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T12:48:22Z","timestamp":1774874902000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-69413-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,20]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["69413"],"URL":"https:\/\/doi.org\/10.1038\/s41467-026-69413-0","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,20]]},"assertion":[{"value":"19 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"R.B.J. has served as an advisor to ViiV Healthcare and received payment for this role. The remaining authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2975"}}