{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T22:59:01Z","timestamp":1792277941177,"version":"4.4.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2018,12,18]],"date-time":"2018-12-18T00:00:00Z","timestamp":1545091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100008615","name":"UNC Lineberger Comprehensive Cancer Center","doi-asserted-by":"publisher","award":["P30 CA16068"],"award-info":[{"award-number":["P30 CA16068"]}],"id":[{"id":"10.13039\/100008615","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Human immunodeficiency virus type 1 (HIV-1) populations are detected in cerebrospinal fluid (CSF) of some people on suppressive antiretroviral therapy (ART). Detailed analysis of these populations may reveal whether they are produced by central nervous system (CNS) reservoirs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We performed a study of 101 asymptomatic participants on stable ART. HIV-1 RNA concentrations were cross-sectionally measured in CSF and plasma. In participants with CSF HIV-1 RNA concentrations sufficient for analysis, viral populations were genetically and phenotypically characterized over multiple time points.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>For 6% of participants (6 of 101), the concentration of HIV-1 RNA in their CSF was \u22650.5 log copies\/mL above that of plasma (ie, CSF escape). We generated viral envelope sequences from CSF of 3 participants. One had a persistent CSF escape population that was macrophage-tropic, partially drug resistant, genetically diverse, and closely related to a minor macrophage-tropic lineage present in the blood prior to viral suppression and enriched for after ART. Two participants (1 suppressed and 1 not) had transient CSF escape populations that were R5 T cell-tropic with little genetic diversity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Extensive analysis of viral populations in 1 participant revealed that CSF escape was from a persistently replicating population, likely in macrophages\/microglia, present in the CNS over 3 years of ART. CSF escape in 2 other participants was likely produced by trafficking and transient expansion of infected T cells in the CNS. Our results show that CNS reservoirs can persist during ART and that CSF escape is not exclusively produced by replicating CNS reservoirs.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciy1066","type":"journal-article","created":{"date-parts":[[2018,12,12]],"date-time":"2018-12-12T15:11:47Z","timestamp":1544627507000},"page":"1345-1352","source":"Crossref","is-referenced-by-count":85,"title":["Human Immunodeficiency Virus Type 1 RNA Detected in the Central Nervous System (CNS) After Years of Suppressive Antiretroviral Therapy Can Originate from a Replicating CNS Reservoir or Clonally Expanded Cells"],"prefix":"10.1093","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9603-574X","authenticated-orcid":false,"given":"Sarah B","family":"Joseph","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura P","family":"Kincer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie M","family":"Bowman","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, School of Medicine, University of North Carolina at Chapel Hill, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Evans","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, School of Medicine, University of North Carolina at Chapel Hill, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Vinikoor","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, School of Medicine, University of North Carolina at Chapel Hill, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher K","family":"Lippincott","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Gissl\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Sahlgrenska Academy at the University of Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Spudich","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prema","family":"Menezes","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, School of Medicine, University of North Carolina at Chapel Hill, Maryland"},{"name":"University of North Carolina Center for AIDS Research, University of North Carolina at Chapel Hill, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Robertson","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of North Carolina at Chapel Hill, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancie","family":"Archin","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, School of Medicine, University of North Carolina at Chapel Hill, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Kashuba","sequence":"additional","affiliation":[{"name":"University of North Carolina Center for AIDS Research, University of North Carolina at Chapel Hill, San Francisco"},{"name":"Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph J","family":"Eron","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, School of Medicine, University of North Carolina at Chapel Hill, Maryland"},{"name":"University of North Carolina Center for AIDS Research, University of North Carolina at Chapel Hill, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard W","family":"Price","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Swanstrom","sequence":"additional","affiliation":[{"name":"University of North Carolina Center for AIDS Research, University of North Carolina at Chapel Hill, San Francisco"},{"name":"Department of Biochemistry and Biophysics, University of North Carolina at Chapel 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