{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T07:46:44Z","timestamp":1790149604017,"version":"4.0.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1006283","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2017,4,3]],"date-time":"2017-04-03T00:00:00Z","timestamp":1491177600000}}],"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2017,3,22]],"date-time":"2017-03-22T00:00:00Z","timestamp":1490140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["HHSN261200800001E"],"award-info":[{"award-number":["HHSN261200800001E"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["HHSN261200800001E"],"award-info":[{"award-number":["HHSN261200800001E"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Leidos Biomedical Research, Inc.","award":["12XS647"],"award-info":[{"award-number":["12XS647"]}]},{"name":"Leidos Biomedical Research, Inc.","award":["13SX110"],"award-info":[{"award-number":["13SX110"]}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP 115715"],"award-info":[{"award-number":["OPP 115715"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","award":["HHMI Medical Research Fellows Program"],"award-info":[{"award-number":["HHMI Medical Research Fellows Program"]}],"id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["NIH Intramural Program"],"award-info":[{"award-number":["NIH Intramural Program"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["NIH Intramural Program"],"award-info":[{"award-number":["NIH Intramural Program"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["Research Professor of the American Cancer Society"],"award-info":[{"award-number":["Research Professor of the American Cancer Society"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"DOI":"10.1371\/journal.ppat.1006283","type":"journal-article","created":{"date-parts":[[2017,3,22]],"date-time":"2017-03-22T23:58:38Z","timestamp":1490227118000},"page":"e1006283","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":246,"title":["Proviruses with identical sequences comprise a large fraction of the replication-competent HIV reservoir"],"prefix":"10.1371","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5905-2049","authenticated-orcid":true,"given":"John K.","family":"Bui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele D.","family":"Sobolewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon F.","family":"Keele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Spindler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0470-9880","authenticated-orcid":true,"given":"Andrew","family":"Musick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Wiegand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2777-7376","authenticated-orcid":true,"given":"Brian T.","family":"Luke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen H.","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Coffin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary F.","family":"Kearney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Mellors","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2017,3,22]]},"reference":[{"issue":"14","key":"ref1","doi-asserted-by":"crossref","first-page":"6508","DOI":"10.1128\/JVI.75.14.6508-6516.2001","article-title":"Decay kinetics of human immunodeficiency virus-specific CD8+ T cells in peripheral blood after initiation of highly active antiretroviral therapy","volume":"75","author":"JP Casazza","year":"2001","journal-title":"Journal of Virology"},{"issue":"5341","key":"ref2","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1126\/science.278.5341.1295","article-title":"Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy","volume":"278","author":"D Finzi","year":"1997","journal-title":"Science"},{"issue":"5341","key":"ref3","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":"5","key":"ref4","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/8394","article-title":"Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy","volume":"5","author":"D Finzi","year":"1999","journal-title":"Nature Medicine"},{"issue":"6629","key":"ref5","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":"6","key":"ref6","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/nm880","article-title":"Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells","volume":"9","author":"JD Siliciano","year":"2003","journal-title":"Nature Medicine"},{"issue":"3","key":"ref7","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1128\/JVI.02139-15","article-title":"Origin of Rebound Plasma HIV Includes Cells with Identical Proviruses That Are Transcriptionally Active before Stopping of Antiretroviral Therapy","volume":"90","author":"MF Kearney","year":"2016","journal-title":"Journal of Virology"},{"issue":"43","key":"ref8","doi-asserted-by":"crossref","first-page":"16725","DOI":"10.1073\/pnas.0804192105","article-title":"HIV rebounds from latently infected cells, rather than from continuing low-level replication","volume":"105","author":"B Joos","year":"2008","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"3","key":"ref9","doi-asserted-by":"crossref","first-page":"e1004010","DOI":"10.1371\/journal.ppat.1004010","article-title":"Lack of detectable HIV-1 molecular evolution during suppressive antiretroviral therapy","volume":"10","author":"MF Kearney","year":"2014","journal-title":"PLOS Pathogens"},{"issue":"6193","key":"ref10","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1126\/science.1254194","article-title":"HIV latency. Specific HIV integration sites are linked to clonal expansion and persistence of infected cells","volume":"345","author":"F Maldarelli","year":"2014","journal-title":"Science"},{"issue":"6196","key":"ref11","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1126\/science.1256304","article-title":"HIV latency. Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection","volume":"345","author":"TA Wagner","year":"2014","journal-title":"Science"},{"issue":"3","key":"ref12","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.cell.2015.01.020","article-title":"HIV-1 integration landscape during latent and active infection","volume":"160","author":"LB Cohn","year":"2015","journal-title":"Cell"},{"key":"ref13","article-title":"Clonally expanded CD4+ T cells can produce infectious HIV-1 in vivo","author":"FR Simonetti","year":"2016","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"49","key":"ref14","doi-asserted-by":"crossref","first-page":"E7908","DOI":"10.1073\/pnas.1617789113","article-title":"Paired quantitative and qualitative assessment of the replication-competent HIV-1 reservoir and comparison with integrated proviral DNA","volume":"113","author":"JC Lorenzi","year":"2016","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"9","key":"ref15","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/nm.4156","article-title":"Defective proviruses rapidly accumulate during acute HIV-1 infection","volume":"22","author":"KM Bruner","year":"2016","journal-title":"Nature Medicine"},{"issue":"11","key":"ref16","doi-asserted-by":"crossref","first-page":"3944","DOI":"10.1128\/JCM.02060-14","article-title":"Improved single-copy assays for quantification of persistent HIV-1 viremia in patients on suppressive antiretroviral therapy","volume":"52","author":"AR Cillo","year":"2014","journal-title":"Journal of Clinical Microbiology"},{"issue":"18","key":"ref17","doi-asserted-by":"crossref","first-page":"10313","DOI":"10.1128\/JVI.01225-12","article-title":"HIV populations are large and accumulate high genetic diversity in a nonlinear fashion","volume":"87","author":"F Maldarelli","year":"2013","journal-title":"Journal of Virology"},{"issue":"4","key":"ref18","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1128\/JCM.02904-15","article-title":"Novel Assays for Measurement of Total Cell-Associated HIV-1 DNA and RNA","volume":"54","author":"F Hong","year":"2016","journal-title":"Journal of Clinical Microbiology"},{"key":"ref19","first-page":"3","article-title":"Enhanced culture assay for detection and quantitation of latently infected, resting CD4+ T-cells carrying replication-competent virus in HIV-1-infected individuals","volume":"304","author":"JD Siliciano","year":"2005","journal-title":"Methods in Molecular Biology"},{"key":"ref20","first-page":"III-102","article-title":"Human Retroviruses and AIDS 1998: A Compilation and Analysis of Nucleic Acid and Amino Acid Sequences","author":"B Korber","year":"1998"},{"issue":"1","key":"ref21","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1128\/JCM.43.1.406-413.2005","article-title":"Multiple, linked human immunodeficiency virus type 1 drug resistance mutations in treatment-experienced patients are missed by standard genotype analysis","volume":"43","author":"S Palmer","year":"2005","journal-title":"Journal of Clinical Microbiology"},{"issue":"4","key":"ref22","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1097\/QAD.0b013e3282f29478","article-title":"Frequent polymorphism at drug resistance sites in HIV-1 protease and reverse transcriptase","volume":"22","author":"M Kearney","year":"2008","journal-title":"AIDS"},{"issue":"6","key":"ref23","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1084\/jem.20090378","article-title":"Genetic identity, biological phenotype, and evolutionary pathways of transmitted\/founder viruses in acute and early HIV-1 infection","volume":"206","author":"JF Salazar-Gonzalez","year":"2009","journal-title":"The Journal of Experimental Medicine"},{"issue":"3","key":"ref24","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":"YC Ho","year":"2013","journal-title":"Cell"},{"issue":"19","key":"ref25","doi-asserted-by":"crossref","first-page":"7078","DOI":"10.1073\/pnas.1402873111","article-title":"Quantification of HIV-1 latency reversal in resting CD4+ T cells from patients on suppressive antiretroviral therapy","volume":"111","author":"AR Cillo","year":"2014","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"2","key":"ref26","doi-asserted-by":"crossref","first-page":"e1003174","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 Pathogens"},{"key":"ref27","article-title":"Defective proviruses rapidly accumulate during acute HIV-1 infection","author":"KM Bruner","year":"2016","journal-title":"Nature medicine"},{"issue":"8","key":"ref28","doi-asserted-by":"crossref","first-page":"5087","DOI":"10.1128\/JVI.69.8.5087-5094.1995","article-title":"Lower in vivo mutation rate of human immunodeficiency virus type 1 than that predicted from the fidelity of purified reverse transcriptase","volume":"69","author":"LM Mansky","year":"1995","journal-title":"Journal of Virology"},{"issue":"4882","key":"ref29","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1126\/science.2460924","article-title":"Fidelity of HIV-1 reverse transcriptase","volume":"242","author":"BD Preston","year":"1988","journal-title":"Science"},{"issue":"1","key":"ref30","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1128\/JVI.73.1.152-160.1999","article-title":"Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination","volume":"73","author":"KS Lole","year":"1999","journal-title":"Journal of Virology"},{"issue":"12","key":"ref31","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1038\/nbt1371","article-title":"Bioinformatics prediction of HIV coreceptor usage","volume":"25","author":"T Lengauer","year":"2007","journal-title":"Nature Biotechnology"},{"issue":"13","key":"ref32","doi-asserted-by":"crossref","first-page":"6441","DOI":"10.1128\/JVI.00591-06","article-title":"Residual human immunodeficiency virus type 1 viremia in some patients on antiretroviral therapy is dominated by a small number of invariant clones rarely found in circulating CD4+ T cells","volume":"80","author":"JR Bailey","year":"2006","journal-title":"Journal of Virology"},{"issue":"23","key":"ref33","doi-asserted-by":"crossref","first-page":"9403","DOI":"10.1073\/pnas.0903107106","article-title":"Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy","volume":"106","author":"JB Dinoso","year":"2009","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"6","key":"ref34","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1086\/650749","article-title":"Short-course raltegravir intensification does not reduce persistent low-level viremia in patients with HIV-1 suppression during receipt of combination antiretroviral therapy. Clinical Infectious Diseases: an official publication of the","volume":"50","author":"D McMahon","year":"2010","journal-title":"Infectious Diseases Society of America"},{"issue":"2","key":"ref35","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1086\/649569","article-title":"No evidence for decay of the latent reservoir in HIV-1-infected patients receiving intensive enfuvirtide-containing antiretroviral therapy","volume":"201","author":"RT Gandhi","year":"2010","journal-title":"The Journal of Infectious Diseases"},{"issue":"15","key":"ref36","doi-asserted-by":"crossref","first-page":"9625","DOI":"10.1128\/JVI.79.15.9625-9634.2005","article-title":"Evidence that low-level viremias during effective highly active antiretroviral therapy result from two processes: expression of archival virus and replication of virus","volume":"79","author":"NH Tobin","year":"2005","journal-title":"Journal of Virology"},{"issue":"8","key":"ref37","doi-asserted-by":"crossref","first-page":"e1005689","DOI":"10.1371\/journal.ppat.1005689","article-title":"Evaluating Clonal Expansion of HIV-Infected Cells: Optimization of PCR Strategies to Predict Clonality","volume":"12","author":"SB Laskey","year":"2016","journal-title":"PLOS Pathogens"},{"issue":"2","key":"ref38","doi-asserted-by":"crossref","first-page":"e1006230","DOI":"10.1371\/journal.ppat.1006230","article-title":"Ex vivo activation of CD4+ T-cells from donors on suppressive ART can lead to sustained production of infectious HIV-1 from a subset of infected cells","volume":"13","author":"JK Bui","year":"2017","journal-title":"PLOS Pathogens"},{"issue":"5197","key":"ref39","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1126\/science.7824947","article-title":"HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy","volume":"267","author":"JM Coffin","year":"1995","journal-title":"Science"},{"issue":"5255","key":"ref40","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1126\/science.271.5255.1582","article-title":"HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time","volume":"271","author":"AS Perelson","year":"1996","journal-title":"Science"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0079-6603(02)71042-8","article-title":"Molecular basis of fidelity of DNA synthesis and nucleotide specificity of retroviral reverse transcriptases","volume":"71","author":"L Menendez-Arias","year":"2002","journal-title":"Progress in Nucleic Acid Research and Molecular Biology"},{"issue":"4882","key":"ref42","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1126\/science.2460925","article-title":"The accuracy of reverse transcriptase from HIV-1","volume":"242","author":"JD Roberts","year":"1988","journal-title":"Science"},{"issue":"8","key":"ref43","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1038\/nm.1972","article-title":"HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation","volume":"15","author":"N Chomont","year":"2009","journal-title":"Nature Medicine"},{"issue":"4","key":"ref44","doi-asserted-by":"crossref","first-page":"ofv123","DOI":"10.1093\/ofid\/ofv123","article-title":"Designing and Interpreting Limiting Dilution Assays: General Principles and Applications to the Latent Reservoir for Human Immunodeficiency Virus-1","volume":"2","author":"DI Rosenbloom","year":"2015","journal-title":"Open Forum Infectious Diseases"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s12977-015-0212-2","article-title":"Well-mixed plasma and tissue viral populations in RT-SHIV-infected macaques implies a lack of viral replication in the tissues during antiretroviral therapy","volume":"12","author":"MF Kearney","year":"2015","journal-title":"Retrovirology"},{"issue":"4","key":"ref46","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1093\/bioinformatics\/16.4.400","article-title":"Detecting hypermutations in viral sequences with an emphasis on G\u2014> A hypermutation","volume":"16","author":"PP Rose","year":"2000","journal-title":"Bioinformatics"},{"issue":"11","key":"ref47","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1086\/503914","article-title":"Web resources for HIV type 1 genotypic-resistance test interpretation. Clinical Infectious Diseases: an official publication of the","volume":"42","author":"TF Liu","year":"2006","journal-title":"Infectious Diseases Society of America"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1006283","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2017,4,3]],"date-time":"2017-04-03T00:00:00Z","timestamp":1491177600000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.ppat.1006283","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,4]],"date-time":"2020-10-04T07:27:41Z","timestamp":1601796461000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1006283"}},"subtitle":[],"editor":[{"given":"Susan R.","family":"Ross","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,3,22]]},"references-count":47,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2017,3,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1006283","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.ppat.1006283","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,22]]}}}