{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:24:15Z","timestamp":1772173455235,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1013433","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000}}],"reference-count":94,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Drug treatment can control HIV-1 replication, but it cannot cure infection. This is because of a long-lived population of quiescent infected cells, known as the latent reservoir (LR), that can restart active replication even after decades of successful drug treatment. Many cells in the LR belong to highly expanded clones, but the processes underlying the clonal structure of the LR are unclear. Understanding the dynamics of the LR and the keys to its persistence is critical for developing an HIV-1 cure. Here we develop a quantitative model of LR dynamics that fits available patient data over time scales spanning from days to decades. We show that the interplay between antigenic stimulation and clonal heterogeneity shapes the dynamics of the LR. In particular, we find that large clones play a central role in long-term persistence, even though they rarely reactivate. Our results could inform the development of HIV-1 cure strategies.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1013433","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T17:45:27Z","timestamp":1757958327000},"page":"e1013433","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clonal heterogeneity and antigenic stimulation shape persistence of the latent reservoir of HIV"],"prefix":"10.1371","volume":"21","author":[{"given":"Marco Garcia","family":"Noceda","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8198-2418","authenticated-orcid":true,"given":"Gargi","family":"Kher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shikhar","family":"Uttam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1467-421X","authenticated-orcid":true,"given":"John P.","family":"Barton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"issue":"4599","key":"pcbi.1013433.ref001","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1126\/science.6189183","article-title":"Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS)","volume":"220","author":"F Barr\u00e9-Sinoussi","year":"1983","journal-title":"Science"},{"issue":"4599","key":"pcbi.1013433.ref002","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1126\/science.6601823","article-title":"Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS)","volume":"220","author":"RC Gallo","year":"1983","journal-title":"Science"},{"issue":"1","key":"pcbi.1013433.ref003","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1023\/A:1021070512287","article-title":"HIV-1 replication","volume":"26","author":"EO Freed","year":"2001","journal-title":"Somatic Cell and Molecular Genetics"},{"key":"pcbi.1013433.ref004","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/2052-8426-2-20","article-title":"Making sense of how HIV kills infected CD4 T cells: implications for HIV cure","volume":"2","author":"NW Cummins","year":"2014","journal-title":"Mol Cell Ther"},{"issue":"1","key":"pcbi.1013433.ref005","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a007096","article-title":"HIV latency","volume":"1","author":"RF Siliciano","year":"2011","journal-title":"Cold Spring Harb Perspect Med"},{"issue":"5341","key":"pcbi.1013433.ref006","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1126\/science.278.5341.1291","article-title":"Recovery of replication-competent HIV despite prolonged suppression of plasma viremia","volume":"278","author":"JK Wong","year":"1997","journal-title":"Science"},{"issue":"12","key":"pcbi.1013433.ref007","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1038\/nm1295-1284","article-title":"In vivo fate of HIV-1-infected T cells: quantitative analysis of the transition to stable latency","volume":"1","author":"TW Chun","year":"1995","journal-title":"Nat Med"},{"issue":"6629","key":"pcbi.1013433.ref008","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/387183a0","article-title":"Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection","volume":"387","author":"TW Chun","year":"1997","journal-title":"Nature"},{"issue":"2","key":"pcbi.1013433.ref009","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1003174","article-title":"Comparative analysis of measures of viral reservoirs in HIV-1 eradication studies","volume":"9","author":"S Eriksson","year":"2013","journal-title":"PLoS Pathog"},{"issue":"12","key":"pcbi.1013433.ref010","doi-asserted-by":"crossref","first-page":"785","DOI":"10.2217\/fvl-2016-0093","article-title":"HIV-1 latent reservoir: size matters","volume":"11","author":"F Hodel","year":"2016","journal-title":"Future Virol"},{"issue":"4","key":"pcbi.1013433.ref011","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.tim.2015.01.013","article-title":"Towards an HIV-1 cure: measuring the latent reservoir","volume":"23","author":"KM Bruner","year":"2015","journal-title":"Trends Microbiol"},{"issue":"3","key":"pcbi.1013433.ref012","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.cell.2013.09.020","article-title":"Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure","volume":"155","author":"Y-C Ho","year":"2013","journal-title":"Cell"},{"issue":"6193","key":"pcbi.1013433.ref013","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1126\/science.1254194","article-title":"HIV latency. 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