{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:49:29Z","timestamp":1792086569662,"version":"4.4.0"},"reference-count":63,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"NIH Bench to Bedside Program","award":["U01AI125003-05S1"],"award-info":[{"award-number":["U01AI125003-05S1"]}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["Contract Number: 75N91019D00024"],"award-info":[{"award-number":["Contract Number: 75N91019D00024"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Opportunistic infections in the central nervous system (CNS), such as cryptococcal meningitis (CM) have profound consequences for people living with HIV-1 (PWH), including blood-brain barrier impairment and neuroinflammation. To investigate how CM may shape the HIV-1 populations in the CNS, we characterized viral variants in the blood and cerebrospinal fluid (CSF) compartments in PWH with active CM. Thirty-nine participants with CM had paired plasma and CSF viral load measurements prior to the start of anti-retroviral therapy (pre-ART), with overall significantly higher HIV-1 viral loads in plasma compared to the CSF. Among those with CSF pleocytosis, CSF viral loads were relatively higher and CCR5 coreceptor-utilizing HIV-1 were more frequently detected. To investigate whether these differences were due to sustained HIV-1 replication in the CNS that generated genetically distinct viral lineages in the CSF (i.e., viral compartmentalization), we characterized pre-ART HIV-1\n                    <jats:italic>env<\/jats:italic>\n                    populations in a subgroup of eighteen PWH with CSF HIV-1 RNA levels\u2009&gt;\u2009blood (N\u2009=\u20099) and CSF RNA levels\u2009&lt;\u2009blood (N\u2009=\u20099). Compartmentalization between CSF and plasma viral populations was detected in participants from both groups and was associated with higher interleukin-2 (IL-2) levels in CSF. In some cases, HIV-1 populations in CSF were compartmentalized from plasma, were exclusively macrophage-tropic and reached levels exceeding 10\n                    <jats:sup>5<\/jats:sup>\n                    copies\/ml CSF. In other cases, HIV-1 infected cells trafficking across the plasma and CSF compartments seemed the most likely source of virus in the CSF. Post-ART analysis in one participant demonstrated emergence of distinct HIV-1 populations. This study demonstrates that opportunistic infections may have diverse effects in shaping HIV-1 viral populations.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014697","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:30:19Z","timestamp":1792085419000},"page":"e1014697","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["HIV-1 compartmentalization in the central nervous system during cryptococcal meningitis: Analysis of viral, fungal, and host factors"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0991-0011","authenticated-orcid":true,"given":"Maura","family":"Manion","sequence":"first","affiliation":[{"name":"Intramural Clinical Management and Operations Branch, Office of the Clinical Director, National Institute of Allergy and Infectious Disease (NIAID), NIH","place":["Bethesda, Maryland, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille M.","family":"Lange","sequence":"additional","affiliation":[{"name":"HIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health","place":["Frederick, Maryland, United States of America"],"department":["Clinical Retrovirology Section"]},{"name":"HENYIDA LLC","place":["Lewes, Delaware, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana M.","family":"Ortega-Villa","sequence":"additional","affiliation":[{"name":"Office of Biostatistics Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health","place":["Bethesda, Maryland, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Fennessey","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research","place":["Frederick, Maryland, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon F.","family":"Keele","sequence":"additional","affiliation":[{"name":"AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research","place":["Frederick, Maryland, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Moeser","sequence":"additional","affiliation":[{"name":"University of North Carolina","place":["Chapel Hill, North Carolina, United States of America"],"department":["Department of Microbiology and Immunology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Highbarger","sequence":"additional","affiliation":[{"name":"Virus Isolation and Serology Laboratory, Frederick National Laboratory for Cancer Research","place":["Frederick, Maryland, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristi","family":"Huik","sequence":"additional","affiliation":[{"name":"HIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health","place":["Frederick, Maryland, United States of America"],"department":["Clinical Retrovirology Section"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Lindo","sequence":"additional","affiliation":[{"name":"HIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health","place":["Frederick, Maryland, United States of America"],"department":["Clinical Retrovirology Section"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Gonsalves","sequence":"additional","affiliation":[{"name":"HIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health","place":["Frederick, Maryland, United States of America"],"department":["Clinical Retrovirology Section"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2539-4029","authenticated-orcid":true,"given":"James","family":"Virga","sequence":"additional","affiliation":[{"name":"HIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health","place":["Frederick, Maryland, United States of America"],"department":["Clinical Retrovirology Section"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Meya","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Health Sciences Makerere University","place":["Kampala, Uganda"],"department":["Department of Medicine"]},{"name":"University of Minnesota","place":["Minneapolis, Minnesota, United States of America"],"department":["Department of Medicine and International Health"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah B.","family":"Joseph","sequence":"additional","affiliation":[{"name":"University of North Carolina","place":["Chapel Hill, North Carolina, United States of America"],"department":["Department of Microbiology and Immunology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Boulware","sequence":"additional","affiliation":[{"name":"University of Minnesota","place":["Minneapolis, Minnesota, United States of America"],"department":["Department of Medicine and International Health"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irini","family":"Sereti","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Disease (NIAID), NIH","place":["Bethesda, Maryland, United States of America"],"department":["Laboratory of Immunoregulation, Division of Intramural Research"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Maldarelli","sequence":"additional","affiliation":[{"name":"HIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health","place":["Frederick, Maryland, United States of America"],"department":["Clinical Retrovirology Section"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"issue":"9","key":"ppat.1014697.ref001","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.aav2045","article-title":"No evidence of ongoing HIV replication or compartmentalization in tissues during combination antiretroviral therapy: Implications for HIV eradication","volume":"5","author":"G Bozzi","year":"2019","journal-title":"Sci Adv"},{"issue":"4","key":"ppat.1014697.ref002","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1172\/JCI134815","article-title":"HIV persists throughout deep tissues 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cerebrospinal fluid and a high prevalence of CXCR4-using variants","volume":"34","author":"K Sojane","year":"2018","journal-title":"AIDS Res Hum Retroviruses"},{"issue":"8","key":"ppat.1014697.ref030","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1097\/00002030-200305230-00008","article-title":"Suppression of cerebrospinal fluid HIV burden in antiretroviral naive patients on a potent four-drug antiretroviral regimen","volume":"17","author":"MA Polis","year":"2003","journal-title":"AIDS"},{"issue":"2","key":"ppat.1014697.ref031","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s11011-013-9476-1","article-title":"Predictors of neurocognitive outcomes on antiretroviral therapy after cryptococcal meningitis: a prospective cohort study","volume":"29","author":"RD Carlson","year":"2014","journal-title":"Metab Brain Dis"},{"issue":"18","key":"ppat.1014697.ref032","doi-asserted-by":"crossref","first-page":"10313","DOI":"10.1128\/JVI.01225-12","article-title":"HIV 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