{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:29:04Z","timestamp":1792841344499,"version":"4.5.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T00:00:00Z","timestamp":1636329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Swedish government and county councils","award":["ALFGBG-70150"],"award-info":[{"award-number":["ALFGBG-70150"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The aim of this large multicenter study was to determine variations in cerebrospinal fluid (CSF) HIV-RNA in different phases of untreated human immunodeficiency virus type 1 (HIV-1) infection and its associations with plasma HIV-RNA and other biomarkers.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Treatment naive adults with available CSF HIV-RNA quantification were included and divided into groups representing significant disease phases. Plasma HIV-RNA, CSF white blood cell count (WBC), neopterin, and albumin ratio were included when available.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In total, 1018 patients were included. CSF HIV-RNA was in median (interquartile range [IQR]) 1.03 log10 (0.37\u20131.86) copies\/mL lower than in plasma, and correlated with plasma HIV-RNA (r\u00a0=\u00a00.44, P\u00a0&amp;lt;\u00a0.01), neopterin concentration in CSF (r\u00a0=\u00a00.49, P\u00a0&amp;lt;\u00a0.01) and in serum (r\u00a0=\u00a00.29, P\u00a0&amp;lt;\u00a0.01), CSF WBC (r\u00a0=\u00a00.34, P\u00a0&amp;lt;\u00a0.01) and albumin ratio (r\u00a0=\u00a00.25, P\u00a0&amp;lt;\u00a0.01). CSF HIV-RNA paralleled plasma HIV-RNA in all groups except neuroasymptomatic patients with advanced immunodeficiency (CD4\u00a0&amp;lt;\u00a0200) and patients with HIV-associated dementia (HAD) or opportunistic central nervous system (CNS) infections. Patients with HAD had the highest CSF HIV-RNA (in median [IQR] 4.73 (3.84\u20135.35) log10 copies\/mL). CSF &amp;gt; plasma discordance was found in 126 of 972 individuals (13%) and varied between groups, from 1% in primary HIV, 11% in neuroasymptomatic groups, up to 30% of patients with HAD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our study confirms previous smaller observations of variations in CSF HIV-RNA in different stages of HIV disease. Overall, CSF HIV-RNA was approximately 1 log10 copies\/mL lower in CSF than in plasma, but CSF discordance was found in a substantial minority of subjects, most commonly in patients with HAD, indicating increasing CNS compartmentalization paralleling disease progression.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciab943","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T12:21:51Z","timestamp":1636114911000},"page":"493-502","source":"Crossref","is-referenced-by-count":33,"title":["Cerebrospinal Fluid Viral Load Across the Spectrum of Untreated Human Immunodeficiency Virus Type 1 (HIV-1) Infection: A Cross-Sectional Multicenter Study"],"prefix":"10.1093","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5594-9040","authenticated-orcid":false,"given":"Gustaf","family":"Ulfhammer","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden"},{"name":"Region V\u00e4stra G\u00f6taland, Sahlgrenska University Hospital, Department of Infectious Diseases , Gothenburg , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvid","family":"Ed\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden"},{"name":"Region V\u00e4stra G\u00f6taland, Sahlgrenska University Hospital, Department of Infectious Diseases , Gothenburg , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Antinori","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Diseases L. Spallanzani , Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce J","family":"Brew","sequence":"additional","affiliation":[{"name":"Departments of Neurology and Immunology, Peter Duncan Neurosciences Unit St Vincent\u2019s Centre for Applied Medical Research, St Vincent\u2019s Hospital, University of New South Wales and University of Notre Dame , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2534-8815","authenticated-orcid":false,"given":"Andrea","family":"Calcagno","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, Department of Medical Sciences, University of Torino , Torino , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Cinque","sequence":"additional","affiliation":[{"name":"Scientific Institute San Raffaele , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"De Zan","sequence":"additional","affiliation":[{"name":"Scientific Institute San Raffaele , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Hagberg","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden"},{"name":"Region V\u00e4stra G\u00f6taland, Sahlgrenska University Hospital, Department of Infectious Diseases , Gothenburg , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Lin","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine, Department of Biomedical Data Science , Palo Alto, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Staffan","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Mathematical Sciences, Chalmers University of Technology , Gothenburg , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiana","family":"Oprea","sequence":"additional","affiliation":[{"name":"Carol Davila University of Medicine and Pharmacy, Victor Babes Clinical Hospital for Infectious and Tropical Diseases , Bucharest , Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"Pinnetti","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Diseases L. Spallanzani , Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Spudich","sequence":"additional","affiliation":[{"name":"Yale University , New Haven, Connecticut , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Trunfio","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, Department of Medical Sciences, University of Torino , Torino , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Winston","sequence":"additional","affiliation":[{"name":"Imperial College , London , United Kingdom and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard W","family":"Price","sequence":"additional","affiliation":[{"name":"University of California at San Francisco , San Francisco, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Gissl\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden"},{"name":"Region V\u00e4stra G\u00f6taland, Sahlgrenska University Hospital, Department of Infectious Diseases , Gothenburg , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,11,8]]},"reference":[{"key":"2022083020585205900_CIT0001","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/1471-2334-5-98","article-title":"Cerebrospinal fluid HIV infection and pleocytosis: relation to systemic infection and antiretroviral treatment.","volume":"5","author":"Spudich","year":"2005","journal-title":"BMC Infect Dis"},{"key":"2022083020585205900_CIT0002","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1093\/infdis\/jis326","article-title":"Central nervous system viral invasion and inflammation during acute HIV infection.","volume":"206","author":"Valcour","year":"2012","journal-title":"J Infect Dis"},{"key":"2022083020585205900_CIT0003","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1097\/QAD.0b013e3283299129","article-title":"Cross-sectional characterization of HIV-1 env compartmentalization in cerebrospinal fluid over the full disease course.","volume":"23","author":"Harrington","year":"2009","journal-title":"AIDS"},{"key":"2022083020585205900_CIT0004","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1097\/00126334-199908010-00003","article-title":"Cerebrospinal fluid viral load, intrathecal immunoactivation, and cerebrospinal fluid monocytic cell count in HIV-1 infection.","volume":"21","author":"Gisslen","year":"1999","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2022083020585205900_CIT0005","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1097\/00042560-199512000-00005","article-title":"Quantifying HIV-1 RNA using the polymerase chain reaction on cerebrospinal fluid and serum of seropositive individuals with and without neurologic abnormalities.","volume":"10","author":"Conrad","year":"1995","journal-title":"J Acquir Immune Defic Syndr Hum Retrovirol"},{"key":"2022083020585205900_CIT0006","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1742-6405-7-15","article-title":"Cerebrospinal fluid neopterin: an informative biomarker of central nervous system immune activation in HIV-1 infection.","volume":"7","author":"Hagberg","year":"2010","journal-title":"AIDS Res Ther"},{"key":"2022083020585205900_CIT0007","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1002\/ana.410420504","article-title":"Relationship between human immunodeficiency virus-associated dementia and viral load in cerebrospinal fluid and brain.","volume":"42","author":"McArthur","year":"1997","journal-title":"Ann Neurol"},{"key":"2022083020585205900_CIT0008","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1086\/514001","article-title":"Levels of human immunodeficiency virus type 1 RNA in cerebrospinal fluid correlate with AIDS dementia stage.","volume":"175","author":"Brew","year":"1997","journal-title":"J Infect Dis"},{"key":"2022083020585205900_CIT0009","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1002\/ana.410420503","article-title":"Cerebrospinal fluid human immunodeficiency virus type 1 RNA levels are elevated in neurocognitively impaired individuals with acquired immunodeficiency syndrome. HIV Neurobehavioral Research Center Group.","volume":"42","author":"Ellis","year":"1997","journal-title":"Ann Neurol"},{"key":"2022083020585205900_CIT0010","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1097\/QAD.0000000000002091","article-title":"Cerebrospinal fluid HIV-1 escape according to different thresholds and underlying comorbidities: is it time to assess the definitions?","volume":"33","author":"Trunfio","year":"2019","journal-title":"AIDS"},{"key":"2022083020585205900_CIT0011","doi-asserted-by":"crossref","first-page":"e116081","DOI":"10.1371\/journal.pone.0116081","article-title":"Cerebrospinal fluid (CSF) neuronal biomarkers across the spectrum of HIV infection: hierarchy of injury and detection.","volume":"9","author":"Peterson","year":"2014","journal-title":"PLoS One"},{"key":"2022083020585205900_CIT0012","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1080\/14737159.2017.1341313","article-title":"Neurofilament light chain protein as a marker of neuronal injury: review of its use in HIV-1 infection and reference values for HIV-negative controls.","volume":"17","author":"Yilmaz","year":"2017","journal-title":"Expert Rev Mol Diagn"},{"key":"2022083020585205900_CIT0013","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1086\/420745","article-title":"Primary HIV type 1 infection.","volume":"38","author":"Kassutto","year":"2004","journal-title":"Clin Infect Dis"},{"key":"2022083020585205900_CIT0014","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1093\/infdis\/jir387","article-title":"Central nervous system immune activation characterizes primary human immunodeficiency virus 1 infection even in participants with minimal cerebrospinal fluid viral burden.","volume":"204","author":"Spudich","year":"2011","journal-title":"J Infect Dis"},{"key":"2022083020585205900_CIT0015","first-page":"134","article-title":"Elite control of HIV Infection: implications for vaccines and treatment.","volume":"15","author":"Walker","year":"2007","journal-title":"Top HIV Med"},{"key":"2022083020585205900_CIT0016","first-page":"1","article-title":"1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults.","volume":"41","year":"1992","journal-title":"MMWR Recomm Rep"},{"key":"2022083020585205900_CIT0017","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1212\/WNL.41.6.778","article-title":"Nomenclature and research case definitions for neurologic manifestations of human immunodeficiency virus-type 1 (HIV-1) infection. Report of a working group of the American Academy of neurology AIDS task force.","volume":"41","year":"1991","journal-title":"Neurology"},{"key":"2022083020585205900_CIT0018","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1212\/01.WNL.0000287431.88658.8b","article-title":"Updated research nosology for HIV-associated neurocognitive disorders.","volume":"69","author":"Antinori","year":"2007","journal-title":"Neurology"},{"key":"2022083020585205900_CIT0019","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1159\/000116919","article-title":"Protein analysis in cerebrospinal fluid. II. Reference values derived from healthy individuals 18-88 years of age.","volume":"33","author":"Blennow","year":"1993","journal-title":"Eur Neurol"},{"key":"2022083020585205900_CIT0020","doi-asserted-by":"crossref","first-page":"e0236162","DOI":"10.1371\/journal.pone.0236162","article-title":"Herpes zoster in HIV-1 infection: The role of CSF pleocytosis in secondary CSF escape and discordance.","volume":"15","author":"Hagberg","year":"2020","journal-title":"PLoS One"},{"key":"2022083020585205900_CIT0021","doi-asserted-by":"crossref","first-page":"e0250987","DOI":"10.1371\/journal.pone.0250987","article-title":"Compartmentalization of cerebrospinal fluid inflammation across the spectrum of untreated HIV-1 infection, central nervous system injury and viral suppression.","volume":"16","author":"Gisslen","year":"2021","journal-title":"PLoS One"},{"key":"2022083020585205900_CIT0022","doi-asserted-by":"crossref","first-page":"e88591","DOI":"10.1371\/journal.pone.0088591","article-title":"Biomarker evidence of axonal injury in neuroasymptomatic HIV-1 patients.","volume":"9","author":"Jessen Krut","year":"2014","journal-title":"PLoS One"},{"key":"2022083020585205900_CIT0023","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1086\/518043","article-title":"Elevated cerebrospinal fluid neurofilament light protein concentrations predict the development of AIDS dementia complex.","volume":"195","author":"Gisslen","year":"2007","journal-title":"J Infect Dis"},{"key":"2022083020585205900_CIT0024","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1002\/ana.410420502","article-title":"Measuring the \u201cviral load\u201d in cerebrospinal fluid in human immunodeficiency virus infection: window into brain infection?","volume":"42","author":"Price","year":"1997","journal-title":"Ann Neurol"},{"key":"2022083020585205900_CIT0025","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1212\/WNL.54.4.927","article-title":"Cerebrospinal fluid HIV RNA originates from both local CNS and systemic sources.","volume":"54","author":"Ellis","year":"2000","journal-title":"Neurology"},{"key":"2022083020585205900_CIT0026","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1007\/s11904-015-0265-9","article-title":"Compartmentalization, viral evolution, and viral latency of HIV in the CNS.","volume":"12","author":"Bednar","year":"2015","journal-title":"Curr HIV\/AIDS Rep"},{"key":"2022083020585205900_CIT0027","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1128\/JVI.01863-09","article-title":"Compartmentalization and clonal amplification of HIV-1 variants in the cerebrospinal fluid during primary infection.","volume":"84","author":"Schnell","year":"2010","journal-title":"J Virol"},{"key":"2022083020585205900_CIT0028","article-title":"Blood-brain barrier impairment in patients living with HIV: predictors and associated biomarkers.","volume":"11:867","author":"Caligaris","year":"2021","journal-title":"Diagnostics"},{"key":"2022083020585205900_CIT0029","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1086\/517379","article-title":"High human immunodeficiency virus type 1 RNA load in the cerebrospinal fluid from patients with lymphocytic meningitis.","volume":"177","author":"Morris","year":"1998","journal-title":"J Infect Dis"},{"key":"2022083020585205900_CIT0030","doi-asserted-by":"crossref","first-page":"e0192060","DOI":"10.1371\/journal.pone.0192060","article-title":"Tuberculous meningitis is associated with higher cerebrospinal HIV-1 viral loads compared to other HIV-1-associated meningitides.","volume":"13","author":"Seipone","year":"2018","journal-title":"PLoS One"},{"key":"2022083020585205900_CIT0031","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1186\/1752-1947-5-465","article-title":"Lyme neuroborreliosis in HIV-1 positive men successfully treated with oral doxycycline: a case series and literature review.","volume":"5","author":"Bremell","year":"2011","journal-title":"J Med Case Rep"},{"key":"2022083020585205900_CIT0032","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s15010-019-01268-8","article-title":"Cerebrospinal fluid compartmentalization of HIV-1 and correlation with plasma viral load and blood-brain barrier damage","volume":"47","author":"Bavaro","year":"2019","journal-title":"Infection"},{"key":"2022083020585205900_CIT0033","doi-asserted-by":"crossref","first-page":"e1002286","DOI":"10.1371\/journal.ppat.1002286","article-title":"HIV-1 replication in the central nervous system occurs in two distinct cell types.","volume":"7","author":"Schnell","year":"2011","journal-title":"PLoS Pathog"},{"key":"2022083020585205900_CIT0034","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1002\/JLB.2RI0517-200R","article-title":"The evolution of HIV-1 entry phenotypes as a guide to changing target cells.","volume":"103","author":"Joseph","year":"2018","journal-title":"J Leukoc Biol"},{"key":"2022083020585205900_CIT0035","doi-asserted-by":"crossref","first-page":"S171","DOI":"10.1097\/QAD.0000000000002253","article-title":"What can characterization of cerebrospinal fluid escape populations teach us about viral reservoirs in the central nervous system?","volume":"33","author":"Joseph","year":"2019","journal-title":"AIDS"},{"key":"2022083020585205900_CIT0036","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1177\/135965350601100707","article-title":"Cerebrospinal fluid viral loads reach less than 2 copies\/ml in HIV-1-infected patients with effective antiretroviral therapy.","volume":"11","author":"Yilmaz","year":"2006","journal-title":"Antivir Ther"},{"key":"2022083020585205900_CIT0037","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":"Polis","year":"2003","journal-title":"AIDS"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciab943\/42332609\/ciab943.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/75\/3\/493\/45627331\/ciab943.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/75\/3\/493\/45627331\/ciab943.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T21:53:23Z","timestamp":1661896403000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/75\/3\/493\/6423171"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,8]]},"references-count":37,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,11,8]]},"published-print":{"date-parts":[[2022,8,31]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciab943","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,8,1]]},"published":{"date-parts":[[2021,11,8]]}}}