{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T19:54:52Z","timestamp":1781639692392,"version":"3.54.5"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-AI176596"],"award-info":[{"award-number":["R01-AI176596"]}],"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":["R01-MH118990"],"award-info":[{"award-number":["R01-MH118990"]}],"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":["AI169768"],"award-info":[{"award-number":["AI169768"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Collaboratory of AIDS Researchers for Eradication","award":["UM-1AI164567"],"award-info":[{"award-number":["UM-1AI164567"]}]},{"DOI":"10.13039\/100011072","name":"UNC Center for AIDS Research","doi-asserted-by":"publisher","award":["P30 AI50410"],"award-info":[{"award-number":["P30 AI50410"]}],"id":[{"id":"10.13039\/100011072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008615","name":"UNC Lineberger Comprehensive Cancer Center","doi-asserted-by":"publisher","award":["P01 CA19014"],"award-info":[{"award-number":["P01 CA19014"]}],"id":[{"id":"10.13039\/100008615","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008615","name":"UNC Lineberger Comprehensive Cancer Center","doi-asserted-by":"publisher","award":["P30 CA16086"],"award-info":[{"award-number":["P30 CA16086"]}],"id":[{"id":"10.13039\/100008615","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>HIV-1 RNA typically declines rapidly after initiation of antiretroviral therapy (ART), often reaching undetectable levels within a few weeks and remaining undetectable by standard assays. However, some patients receiving ART have persistent nonsuppressible viremia (NSV) that does not respond to treatment optimization or intensification. NSV can emerge at the time of ART initiation (primary NSV) or after being ART suppressed (secondary NSV). Here, we examine mechanisms producing primary NSV in 4 people undergoing ART.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Blood samples were collected from 4 participants with advanced immunodeficiency who, despite being adherent to ART, required approximately a year or more to become virologically suppressed. Viral RNA and proviral DNA genomes were sequenced to examine HIV drug resistance, genome intactness, and genetic diversity. The ability of HIV Envs to facilitate efficient entry into cells expressing low levels of CD4, a proxy for macrophage tropism, was also assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Before ART, blood contained HIV RNA genomes that were adapted to replication in CD4+ T cells and rapidly decayed after ART initiation. During ART, blood contained HIV genomes that were drug sensitive, genetically diverse, and macrophage tropic; moreover, they were not evolving and often had vpr defects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results suggest that in individuals with primary NSV, ART stopped virus replication, but large pools of long-lived HIV-infected macrophage continued to produce virus. This is mechanistically distinct from secondary NSV produced by CD4+ T-cell clones. Defects in vpr independently accumulated in macrophage-tropic lineages found in 3 participants, suggesting that vpr may affect survival or virus production from HIV-infected macrophage.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiag171","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T11:38:15Z","timestamp":1776339495000},"page":"1005-1014","source":"Crossref","is-referenced-by-count":1,"title":["A New Type of Nonsuppressible Viremia Produced by HIV-Infected Macrophage"],"prefix":"10.1093","volume":"233","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1368-5171","authenticated-orcid":false,"given":"Matthew J","family":"Moeser","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia D","family":"Council","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6241-3937","authenticated-orcid":false,"given":"Laura","family":"Kincer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0687-9661","authenticated-orcid":false,"given":"Ann M","family":"Dennis","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, School of Medicine, University of North Carolina at Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4938-0644","authenticated-orcid":false,"given":"Joseph","family":"Eron","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, School of Medicine, University of North Carolina at Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Wohl","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, School of Medicine, University of North Carolina at Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4678-7713","authenticated-orcid":false,"given":"Claire E","family":"Farel","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, School of Medicine, University of North Carolina at Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4968-5656","authenticated-orcid":false,"given":"Dirk P","family":"Dittmer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, North Carolina"},{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8134-8399","authenticated-orcid":false,"given":"Linda","family":"Pluta","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4609-5263","authenticated-orcid":false,"given":"Julie","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, North Carolina"},{"name":"UNC Center for AIDS Research , University of North Carolina at Chapel Hill,North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9654-769X","authenticated-orcid":false,"given":"Abbas","family":"Mohammadi","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behzad","family":"Etemad","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan Z","family":"Li","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1281-2861","authenticated-orcid":false,"given":"Hugh","family":"McGann","sequence":"additional","affiliation":[{"name":"Waikato Hospital , Hamilton ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3286-798X","authenticated-orcid":false,"given":"Erasmus","family":"Smit","sequence":"additional","affiliation":[{"name":"Waikato Hospital , Hamilton ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0283-6368","authenticated-orcid":false,"given":"Meredith","family":"Clement","sequence":"additional","affiliation":[{"name":"LSU Health Sciences Center , New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2477-788X","authenticated-orcid":false,"given":"Tat","family":"Yau","sequence":"additional","affiliation":[{"name":"LSU Health Sciences Center , New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prema","family":"Menezes","sequence":"additional","affiliation":[{"name":"UNC Center for AIDS Research , University of North Carolina at Chapel Hill,North Carolina"}],"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, North Carolina"},{"name":"UNC Center for AIDS Research , University of North Carolina at Chapel Hill,North 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