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Here, we performed single-genome, near full-length HIV-1 next-generation sequencing to evaluate the proviral landscape in distinct anatomical compartments, including multiple CNS tissues, from 3 ART-treated participants at autopsy. While lymph nodes and, to a lesser extent, gastrointestinal and genitourinary tissues represented tissue hotspots for the persistence of intact proviruses, we also observed intact proviruses in CNS tissue sections, particularly in the basal ganglia. Multi-compartment dissemination of clonal intact and defective proviral sequences occurred across multiple anatomical tissues, including the CNS, and evidence for the clonal proliferation of HIV-1-infected cells was found in the basal ganglia, in the frontal lobe, in the thalamus and in periventricular white matter. Deep analysis of HIV-1 reservoirs in distinct tissues will be informative for advancing HIV-1 cure strategies.<\/jats:p>","DOI":"10.7554\/elife.89837","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T07:17:14Z","timestamp":1690874234000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.89837","source":"Crossref","is-referenced-by-count":7,"title":["Persistence of intact HIV-1 proviruses in the brain during antiretroviral therapy"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4578-6292","authenticated-orcid":true,"given":"Weiwei","family":"Sun","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/053r20n13","id-type":"ROR","asserted-by":"publisher"}],"name":"Ragon Institute of MGH, MIT and Harvard","place":["Cambridge, United 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