{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T09:59:18Z","timestamp":1777543158339,"version":"3.51.4"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>During antiretroviral therapy, people with HIV-1 (PWH) occasionally present with new symptoms and signs of central nervous system (CNS) injury accompanied by higher HIV-1 RNA levels in cerebrospinal fluid (CSF) than in blood, a condition defined as neurosymptomatic CSF escape (NSE). PWH meeting these general criteria but with plasma HIV-1 RNA levels &amp;gt;500 copies\/mL have typically been assumed to be experiencing systemic treatment failure without special consideration for HIV-1 dynamics in the CNS. Thus, people with CNS-focused treatment failure may receive suboptimal treatment, targeted at controlling replication in the periphery, not the CNS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We genetically and phenotypically characterized HIV-1 RNA in the CSF and blood of PWH (N = 9) undergoing antiretroviral therapy who met definitions of NSE and systemic treatment failure, and we defined them as having NSE high (NSE-h).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>While plasma viral loads were higher during NSE-h than NSE, the conditions have many shared features, including elevated CSF:plasma viral load ratios, higher CSF white blood cell counts, and drug-resistant T-tropic HIV-1 replicating in the CNS. During NSE-h, HIV-1 populations in blood and CSF were genetically equilibrated, indicating that they were not independently replicating in both compartments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>NSE and NSE-h are driven by replication of drug-resistant HIV-1 in CD4+ T cells in the CNS, with NSE-h having higher CSF viral loads reflecting more HIV-1 replication. This suggests that people presenting with neurologic symptoms and treatment failure may be experiencing CNS-focused treatment failure that could require specialized treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ofid\/ofaf659","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T11:47:47Z","timestamp":1761133667000},"source":"Crossref","is-referenced-by-count":1,"title":["Neurosymptomatic Cerebrospinal Fluid Escape Is a Central Nervous System\u2013Focused Form of Antiretroviral Therapy Treatment Failure"],"prefix":"10.1093","volume":"13","author":[{"given":"Laura P","family":"Kincer","sequence":"first","affiliation":[{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 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,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serena","family":"Spudich","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale University , New Haven, Connecticut ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magnus","family":"Gissl\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg , Gothenburg ,","place":["Sweden"]},{"name":"Department of Infectious Diseases, Region V\u00e4stra G\u00f6taland, Sahlgrenska University Hospital , Gothenburg ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard W","family":"Price","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California San Francisco , San Francisco, California 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