{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T22:58:46Z","timestamp":1792277926630,"version":"4.4.0"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T00:00:00Z","timestamp":1660003200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1183032"],"award-info":[{"award-number":["1183032"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R21DA055489"],"award-info":[{"award-number":["R21DA055489"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Human immunodeficiency virus (HIV) persistence in blood and tissue reservoirs, including the brain, is a major barrier to HIV cure and possible cause of comorbid disease. However, the size and replication competent nature of the central nervous system (CNS) reservoir is unclear. Here, we used the intact proviral DNA assay (IPDA) to provide the first quantitative assessment of the intact and defective HIV reservoir in the brain of people with HIV (PWH).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Total, intact, and defective HIV proviruses were measured in autopsy frontal lobe tissue from viremic (n\u00a0=\u00a018) or virologically suppressed (n\u00a0=\u00a012) PWH. Total or intact\/defective proviruses were measured by detection of HIV <jats:italic>pol<\/jats:italic> or the IPDA, respectively, through use of droplet digital polymerase chain reaction (ddPCR). HIV\u2010seronegative individuals were included as controls (n\u00a0=\u00a06).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Total HIV DNA was present at similar levels in brain tissues from untreated viremic and antiretroviral (ART)\u2010suppressed individuals (median\u00a0=\u00a022.3 vs 26.2 HIV pol copies\/10<jats:sup>6<\/jats:sup> cells), reflecting a stable CNS reservoir of HIV that persists despite therapy. Furthermore, 8 of 10 viremic and 6 of 9 virally suppressed PWH also harbored intact proviruses in the CNS (4.63 vs 12.7 intact copies\/10<jats:sup>6<\/jats:sup> cells). Viral reservoirs in CNS and matched lymphoid tissue were similar in the composition of intact and\/or defective proviruses, albeit at lower levels in the brain. Importantly, CNS resident CD68+ myeloid cells in virally suppressed individuals harbored HIV DNA, directly showing the presence of a CNS resident HIV reservoir.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our results demonstrate the first evidence for an intact, potentially replication competent HIV reservoir in the CNS of virally suppressed PWH. ANN NEUROL 2022;92:532\u2013544<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.26456","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T15:23:28Z","timestamp":1658503408000},"page":"532-544","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["Intact HIV Proviruses Persist in the Brain Despite Viral Suppression with ART"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9683-8905","authenticated-orcid":false,"given":"Catherine R.","family":"Cochrane","sequence":"first","affiliation":[{"name":"Emerging Infections Program, School of Health and Biomedical Sciences RMIT University  Melbourne VIC Australia"},{"name":"Department of Medicine The Royal Melbourne Hospital, The University of Melbourne  Melbourne VIC 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Health and Biomedical Sciences RMIT University  Melbourne VIC Australia"},{"name":"Department of Medicine The Royal Melbourne Hospital, The University of Melbourne  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleks C.","family":"Guanizo","sequence":"additional","affiliation":[{"name":"Emerging Infections Program, School of Health and Biomedical Sciences RMIT University  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma S.","family":"Trollope","sequence":"additional","affiliation":[{"name":"Emerging Infections Program, School of Health and Biomedical Sciences RMIT University  Melbourne VIC Australia"},{"name":"Department of Medicine The Royal Melbourne Hospital, The University of Melbourne  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingling","family":"Zhou","sequence":"additional","affiliation":[{"name":"Emerging Infections Program, School of Health and Biomedical Sciences RMIT University  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Vue","sequence":"additional","affiliation":[{"name":"Emerging Infections Program, School of Health and Biomedical Sciences RMIT University  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lachlan","family":"Senior","sequence":"additional","affiliation":[{"name":"Emerging Infections Program, School of Health and Biomedical Sciences RMIT University  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Wanicek","sequence":"additional","affiliation":[{"name":"Emerging Infections Program, School of Health and Biomedical Sciences RMIT University  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janna Jamal","family":"Eddine","sequence":"additional","affiliation":[{"name":"Emerging Infections Program, School of Health and Biomedical Sciences RMIT University  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4953-9501","authenticated-orcid":false,"given":"Matthew J.","family":"Gartner","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases The University of Melbourne at the Peter Doherty Institute for Infection and Immunity  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0137-6643","authenticated-orcid":false,"given":"Trisha A.","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Emerging Infections Program, School of Health and Biomedical Sciences RMIT University  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5407-7124","authenticated-orcid":false,"given":"Paul R.","family":"Gorry","sequence":"additional","affiliation":[{"name":"Emerging Infections Program, School of Health and Biomedical Sciences RMIT University  Melbourne VIC Australia"},{"name":"Department of Infectious Diseases Alfred Hospital and Monash University  Melbourne VIC Australia"},{"name":"Department of Microbiology and Immunology The University of Melbourne at the Peter Doherty Institute for Infection and Immunity  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0622-1392","authenticated-orcid":false,"given":"Bruce J.","family":"Brew","sequence":"additional","affiliation":[{"name":"Peter Duncan Neurosciences Unit, Departments of Neurology and Immunology St Vincent's Hospital Sydney, University of New South Wales and University of Notre Dame  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0330-8241","authenticated-orcid":false,"given":"Sharon R.","family":"Lewin","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases The University of Melbourne at the Peter Doherty Institute for Infection and Immunity  Melbourne VIC Australia"},{"name":"Department of Infectious Diseases Alfred Hospital and Monash University  Melbourne VIC Australia"},{"name":"Victorian Infectious Diseases Service Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9652-6394","authenticated-orcid":false,"given":"Jacob D.","family":"Estes","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon National Primate Research Centre Oregon Health &amp; Science University  Portland OR 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