{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T01:20:04Z","timestamp":1776475204335,"version":"3.51.2"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1006028","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2018,3,22]],"date-time":"2018-03-22T00:00:00Z","timestamp":1521676800000}}],"reference-count":63,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2018,3,2]],"date-time":"2018-03-02T00:00:00Z","timestamp":1519948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004211","name":"Oxford Martin School, University of Oxford","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004211","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DA033773"],"award-info":[{"award-number":["DA033773"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI035039"],"award-info":[{"award-number":["AI035039"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004211","name":"Oxford Martin School, University of Oxford","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004211","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1006028","type":"journal-article","created":{"date-parts":[[2018,3,2]],"date-time":"2018-03-02T13:23:54Z","timestamp":1519997034000},"page":"e1006028","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Increased T cell trafficking as adjunct therapy for HIV-1"],"prefix":"10.1371","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9987-8160","authenticated-orcid":true,"given":"Helen R.","family":"Fryer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven M.","family":"Wolinsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela R.","family":"McLean","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2018,3,2]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/387188a0","article-title":"Decay characteristics of HIV-1-infected compartments during combination therapy","volume":"387","author":"AS Perelson","year":"1997","journal-title":"Nature"},{"key":"ref2","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"},{"key":"ref3","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":"Nat Med"},{"key":"ref4","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"},{"key":"ref5","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"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1056\/NEJM199905273402102","article-title":"Persistence of HIV-1 transcription in peripheral-blood mononuclear cells in patients receiving potent antiretroviral therapy","volume":"340","author":"MR Furtado","year":"1999","journal-title":"N Engl J Med"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1089\/aid.2016.0253","article-title":"HIV Persistence in Gut-Associated Lymphoid Tissues: Pharmacological Challenges and Opportunities","volume":"33","author":"CG Thompson","year":"2017","journal-title":"AIDS Res Hum Retroviruses"},{"key":"ref8","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":"Nat Med"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"13193","DOI":"10.1073\/pnas.94.24.13193","article-title":"Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy","volume":"94","author":"TW Chun","year":"1997","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref10","first-page":"15109","article-title":"Proc Natl Acad Sci U S A","volume":"96","author":"RT Davey Jr.","year":"1999"},{"key":"ref11","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":"Nat Med"},{"key":"ref12","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":"Nat Med"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nature16933","article-title":"Persistent HIV-1 replication maintains the tissue reservoir during therapy","volume":"530","author":"R Lorenzo-Redondo","year":"2016","journal-title":"Nature"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1097\/COH.0000000000000287","article-title":"Persistent HIV-1 replication during antiretroviral therapy","volume":"11","author":"J Martinez-Picado","year":"2016","journal-title":"Curr Opin HIV AIDS"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1073\/pnas.1318249111","article-title":"Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues","volume":"111","author":"CV Fletcher","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nri3689","article-title":"Follicular dendritic cells: dynamic antigen libraries","volume":"14","author":"BA Heesters","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1056\/NEJMoa1110039","article-title":"Short-course antiretroviral therapy in primary HIV infection","volume":"368","author":"ST Investigators","year":"2013","journal-title":"N Engl J Med"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/nm.2111","article-title":"HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects","volume":"16","author":"MJ Buzon","year":"2010","journal-title":"Nat Med"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/aps.2015.22","article-title":"Progress and challenges in the use of latent HIV-1 reactivating agents","volume":"36","author":"HT Shang","year":"2015","journal-title":"Acta Pharmacol Sin"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S0140-6736(05)67098-5","article-title":"Depletion of latent HIV-1 infection in vivo: a proof-of-concept study","volume":"366","author":"G Lehrman","year":"2005","journal-title":"Lancet"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/nm.3489","article-title":"New ex vivo approaches distinguish effective and ineffective single agents for reversing HIV-1 latency in vivo","volume":"20","author":"CK Bullen","year":"2014","journal-title":"Nat Med"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1093\/infdis\/jis412","article-title":"Effect of histone deacetylase inhibitors on HIV production in latently infected, resting CD4(+) T cells from infected individuals receiving effective antiretroviral therapy","volume":"206","author":"J Blazkova","year":"2012","journal-title":"J Infect Dis"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"e1004287","DOI":"10.1371\/journal.ppat.1004287","article-title":"Histone deacetylase inhibitors impair the elimination of HIV-infected cells by cytotoxic T-lymphocytes","volume":"10","author":"RB Jones","year":"2014","journal-title":"PLoS Pathog"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/nature11286","article-title":"Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy","volume":"487","author":"NM Archin","year":"2012","journal-title":"Nature"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"e1004473","DOI":"10.1371\/journal.ppat.1004473","article-title":"Activation of HIV transcription with short-course vorinostat in HIV-infected patients on suppressive antiretroviral therapy","volume":"10","author":"JH Elliott","year":"2014","journal-title":"PLoS Pathog"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"e13","DOI":"10.1016\/S2352-3018(14)70014-1","article-title":"Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1\/2, single group, clinical trial","volume":"1","author":"TA Rasmussen","year":"2014","journal-title":"Lancet HIV"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1093\/cid\/cit813","article-title":"A pilot study assessing the safety and latency-reversing activity of disulfiram in HIV-1-infected adults on antiretroviral therapy","volume":"58","author":"AM Spivak","year":"2014","journal-title":"Clin Infect Dis"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"e520","DOI":"10.1016\/S2352-3018(15)00226-X","article-title":"Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study","volume":"2","author":"JH Elliott","year":"2015","journal-title":"Lancet HIV"},{"key":"ref29","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"},{"key":"ref30","article-title":"The Spleen Is an HIV-1 Sanctuary During Combined Antiretroviral Therapy","author":"DJ Nolan","year":"2017","journal-title":"AIDS Res Hum Retroviruses"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/nm.4113","article-title":"PD-1(+) and follicular helper T cells are responsible for persistent HIV-1 transcription in treated aviremic individuals","volume":"22","author":"R Banga","year":"2016","journal-title":"Nat Med"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1084\/jem.20121932","article-title":"Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production","volume":"210","author":"M Perreau","year":"2013","journal-title":"J Exp Med"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1089\/aid.2005.21.363","article-title":"Lymphoid follicles are sites of heightened human immunodeficiency virus type 1 (HIV-1) replication and reduced antiretroviral effector mechanisms","volume":"21","author":"JM Folkvord","year":"2005","journal-title":"AIDS Res Hum Retroviruses"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/nm.3781","article-title":"B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers","volume":"21","author":"Y Fukazawa","year":"2015","journal-title":"Nat Med"},{"key":"ref35","article-title":"SIV-producing cells in follicles are partially suppressed by CD8+ cells in vivo","author":"S Li","year":"2016","journal-title":"J Virol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/imr.12396","article-title":"Regulation of germinal center B-cell differentiation","volume":"270","author":"Y Zhang","year":"2016","journal-title":"Immunol Rev"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"6975","DOI":"10.4049\/jimmunol.178.11.6975","article-title":"CTL fail to accumulate at sites of HIV-1 replication in lymphoid tissue","volume":"178","author":"E Connick","year":"2007","journal-title":"J Immunol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"5613","DOI":"10.4049\/jimmunol.1401161","article-title":"Compartmentalization of simian immunodeficiency virus replication within secondary lymphoid tissues of rhesus macaques is linked to disease stage and inversely related to localization of virus-specific CTL","volume":"193","author":"E Connick","year":"2014","journal-title":"J Immunol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.virol.2014.02.008","article-title":"Transcriptional control of HIV latency: cellular signaling pathways, epigenetics, happenstance and the hope for a cure","volume":"454\u2013455","author":"U Mbonye","year":"2014","journal-title":"Virology"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1038\/ni.f.213","article-title":"Orchestrating the orchestrators: chemokines in control of T cell traffic","volume":"9","author":"SK Bromley","year":"2008","journal-title":"Nat Immunol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"613","DOI":"10.3389\/fimmu.2016.00613","article-title":"T Cell Trafficking through Lymphatic Vessels","volume":"7","author":"MC Hunter","year":"2016","journal-title":"Front Immunol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.it.2015.10.005","article-title":"Exit Strategies: S1P Signaling and T Cell Migration","volume":"36","author":"A Baeyens","year":"2015","journal-title":"Trends Immunol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1038\/ni.f.210","article-title":"Moving targets: cell migration inhibitors as new anti-inflammatory therapies","volume":"9","author":"CR Mackay","year":"2008","journal-title":"Nat Immunol"},{"issue":"Suppl 1","key":"ref44","doi-asserted-by":"crossref","first-page":"E86","DOI":"10.1111\/j.1749-6632.2010.05711.x","article-title":"Gut-associated lymphoid tissue, T cell trafficking, and chronic intestinal inflammation","volume":"1207","author":"I Koboziev","year":"2010","journal-title":"Ann N Y Acad Sci"},{"key":"ref45","article-title":"Immunotherapy: Cancer vaccines on the move","author":"J Banchereau","year":"2017","journal-title":"Nat Rev Clin Oncol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"E2874","DOI":"10.1073\/pnas.1424184112","article-title":"Imperfect drug penetration leads to spatial monotherapy and rapid evolution of multidrug resistance","volume":"112","author":"S Moreno-Gamez","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"11514","DOI":"10.1073\/pnas.95.20.11514","article-title":"Drug concentration heterogeneity facilitates the evolution of drug resistance","volume":"95","author":"TB Kepler","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/S0167-5699(97)01036-0","article-title":"A model of lymphocyte recirculation","volume":"18","author":"DJ Stekel","year":"1997","journal-title":"Immunol Today"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/373117a0","article-title":"Viral dynamics in human immunodeficiency virus type 1 infection","volume":"373","author":"X Wei","year":"1995","journal-title":"Nature"},{"key":"ref50","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.02507-16","article-title":"CXCR5-Dependent Entry of CD8 T Cells into Rhesus Macaque B-Cell Follicles Achieved through T-Cell Engineering","volume":"91","author":"VI Ayala","year":"2017","journal-title":"J Virol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nature04444","article-title":"Restoring function in exhausted CD8 T cells during chronic viral infection","volume":"439","author":"DL Barber","year":"2006","journal-title":"Nature"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.chom.2016.02.018","article-title":"A Drug-Free Zone\u2014Lymph Nodes as a Safe Haven for HIV","volume":"19","author":"A Licht","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/1074-7613(95)90162-0","article-title":"Distinct roles of L-selectin and integrins alpha 4 beta 7 and LFA-1 in lymphocyte homing to Peyer's patch-HEV in situ: the multistep model confirmed and refined","volume":"3","author":"RF Bargatze","year":"1995","journal-title":"Immunity"},{"key":"ref54","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.aam7341","article-title":"Virion incorporation of integrin alpha4beta7 facilitates HIV-1 infection and intestinal homing","volume":"2","author":"C Guzzo","year":"2017","journal-title":"Sci Immunol"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1126\/science.aag1276","article-title":"Sustained virologic control in SIV+ macaques after antiretroviral and alpha4beta7 antibody therapy","volume":"354","author":"SN Byrareddy","year":"2016","journal-title":"Science"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.immuni.2014.12.007","article-title":"Tissue-resident memory T cells","volume":"41","author":"JM Schenkel","year":"2014","journal-title":"Immunity"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"891","DOI":"10.3389\/fimmu.2017.00891","article-title":"Anti-Adhesion Therapies in Inflammatory Bowel Disease-Molecular and Clinical Aspects","volume":"8","author":"S Zundler","year":"2017","journal-title":"Front Immunol"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/nri1354","article-title":"Lymphocyte trafficking across high endothelial venules: dogmas and enigmas","volume":"4","author":"M Miyasaka","year":"2004","journal-title":"Nat Rev Immunol"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.immuni.2015.01.013","article-title":"The transcription factor KLF2 restrains CD4(+) T follicular helper cell differentiation","volume":"42","author":"JY Lee","year":"2015","journal-title":"Immunity"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1182\/blood-2007-05-088435","article-title":"HIV-1 induced activation of CD4+ T cells creates new targets for HIV-1 infection in human lymphoid tissue ex vivo","volume":"111","author":"A Biancotto","year":"2008","journal-title":"Blood"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1146\/annurev.immunol.23.021704.115628","article-title":"Chemokines, sphingosine-1-phosphate, and cell migration in secondary lymphoid organs","volume":"23","author":"JG Cyster","year":"2005","journal-title":"Annu Rev Immunol"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/44385","article-title":"Two subsets of memory T lymphocytes with distinct homing potentials and effector functions","volume":"401","author":"F Sallusto","year":"1999","journal-title":"Nature"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1093\/infdis\/jir491","article-title":"The role of migration and domestic transmission in the spread of HIV-1 non-B subtypes in Switzerland","volume":"204","author":"V von Wyl","year":"2011","journal-title":"J Infect Dis"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1006028","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2018,3,22]],"date-time":"2018-03-22T00:00:00Z","timestamp":1521676800000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1006028","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T15:06:42Z","timestamp":1540220802000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1006028"}},"subtitle":[],"editor":[{"given":"Claus O.","family":"Wilke","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2018,3,2]]},"references-count":63,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,3,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1006028","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pcbi.1006028","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,2]]}}}