{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:26:06Z","timestamp":1780410366930,"version":"3.54.1"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ricerca Finalizzata di Rete","award":["NET-2013-02355333"],"award-info":[{"award-number":["NET-2013-02355333"]}]},{"DOI":"10.13039\/100010877","name":"Viiv Healthcare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010877","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>It is debated whether CNS involvement begins during acute human immunodeficiency virus (HIV) infection in persons without meningitis\/encephalitis and whether specific antiretroviral drugs or combinations would be beneficial.<\/jats:p>\n               <jats:p>Neurologically asymptomatic participants enrolled in a randomized and controlled study comparing three combination antiretroviral regimens (tenofovir alafenamide\/emtricitabine plus dolutegravir; darunavir; or both) during primary HIV infection were enrolled. Serum and CSF were collected at baseline and at 12 and 48 (serum only) weeks after treatment initiation. Single molecule array was used to measure neurofilament light chain (NFL), total tau protein (Tau), brain-derived neurotrophic factor, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase. We assessed the longitudinal change in biomarkers over time, in addition to the change in the prevalence of serum NFL concentrations above previously published age-adjusted cut-offs (7\u2005pg\/ml if 5\u201318 years, 10\u2005pg\/ml if 18\u201351 years, 15\u2005pg\/ml if 51\u201361 years, 20\u2005pg\/ml if 61\u201370 years and 35\u2005pg\/ml if &amp;gt;70 years).<\/jats:p>\n               <jats:p>Serum was available from 47 participants at all time points, and CSF was available from 13 participants at baseline and 7 at Week 12. We observed a significant direct serum-to-CSF correlation for NFL (\u03c1 = 0.692, P = 0.009), GFAP (\u03c1 = 0.659, P = 0.014) and brain-derived neurotrophic factor (\u03c1 = 0.587, P = 0.045). Serum (\u03c1 = 0.560, P = 0.046) and CSF NFL (\u03c1 = 0.582, P = 0.037) concentrations were directly associated with CSF HIV RNA levels. We observed a significant decrease over time in serum NFL (P = 0.006) and GFAP (P = 0.006) but not in the other biomarkers. No significant difference was observed among the treatment arms. At baseline, serum and CSF age-adjusted NFL levels were above age-adjusted cut-offs in 23 (48.9%) and four participants (30.8%), respectively; considering serum NFL, this proportion was lower at Weeks 12 (31.9%, P = 0.057) and 48 (27.7%, P = 0.13).<\/jats:p>\n               <jats:p>A relevant proportion of neurologically asymptomatic participants had abnormal CSF and serum NFL levels during primary HIV infection. NFL and GFAP decreased in serum following combination antiretroviral therapy without significant differences among the treatment arms.<\/jats:p>","DOI":"10.1093\/brain\/awae271","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T05:18:22Z","timestamp":1724303902000},"page":"3742-3750","source":"Crossref","is-referenced-by-count":10,"title":["Serum and CSF biomarkers in asymptomatic patients during primary HIV infection: a randomized study"],"prefix":"10.1093","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2534-8815","authenticated-orcid":false,"given":"Andrea","family":"Calcagno","sequence":"first","affiliation":[{"name":"Unit of Infectious Diseases, Department of Medical Sciences, University of Turin , 10149 Turin ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1977-9694","authenticated-orcid":false,"given":"Jessica","family":"Cusato","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology and Pharmacogenetics, University of Turin , 10149 Turin ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Cinque","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, IRCCS Ospedale San Raffaele , 20132 Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Marchetti","sequence":"additional","affiliation":[{"name":"Clinic of Infectious Diseases, Department of Health Sciences, ASST Santi Paolo e Carlo, University of Milan , 20142 Milan ,","place":["Italy"]},{"name":"School of Medicine and Surgery, University of Milan , 20122 Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Bernasconi","sequence":"additional","affiliation":[{"name":"Bicocca Bioinformatics Biostatistics and Bioimaging Centre \u2013 B4 School of Medicine and Surgery, University of Milano-Bicocca , 20900 Monza ,","place":["Italy"]},{"name":"Department of Clinical Research and Innovation, ASST Grande Ospedale Metropolitano Niguarda , 20162 Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8663-719X","authenticated-orcid":false,"given":"Mattia","family":"Trunfio","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, Department of Medical Sciences, University of Turin , 10149 Turin ,","place":["Italy"]},{"name":"HIV Neurobehavioral Research Program, Department of Psychiatry, University of California, UCSD , La Jolla, CA 92093-0021 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Bruzzesi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, IRCCS Ospedale San Raffaele , 20132 Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0375-9990","authenticated-orcid":false,"given":"Stefano","family":"Rusconi","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Milan , 20122 Milan ,","place":["Italy"]},{"name":"SC Malattie Infettive, Ospedale di Legnano, ASST Ovest Milanese , 20025 Legnano ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Gabrieli","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Biomediche e Cliniche (DIBIC) , 20157 Milan 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Absence of cerebrospinal fluid signs of neuronal injury before and after immediate antiretroviral therapy in acute HIV infection","volume":"212","author":"Peluso","year":"2015","journal-title":"J Infect Dis"},{"key":"2025031409274209300_awae271-B10","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1097\/QAI.0000000000002832","article-title":"HIV disease dynamics and markers of inflammation and CNS injury during primary HIV infection and their relationship to cognitive performance","volume":"89","author":"Longino","year":"2022","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2025031409274209300_awae271-B11","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/s41582-023-00813-2","article-title":"Cognitive impairment in people living with HIV: Consensus recommendations for a new approach","volume":"19","author":"Nightingale","year":"2023","journal-title":"Nat Rev Neurol"},{"issue":"Suppl 2","key":"2025031409274209300_awae271-B12","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":"2025031409274209300_awae271-B13","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1097\/QAD.0000000000003825","article-title":"Rapid antiretroviral therapy in primary HIV-1 infection enhances immune recovery","volume":"38","author":"Thornhill","year":"2023","journal-title":"AIDS"},{"key":"2025031409274209300_awae271-B14","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.3389\/fimmu.2019.01749","article-title":"Learning from the exceptions: HIV remission in post-treatment controllers","volume":"10","author":"Etemad","year":"2019","journal-title":"Front Immunol"},{"key":"2025031409274209300_awae271-B15","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s11904-014-0255-3","article-title":"Neuropathogenesis of HIV: From initial neuroinvasion to HIV-associated neurocognitive disorder (HAND)","volume":"12","author":"Zayyad","year":"2015","journal-title":"Curr HIV\/AIDS Rep"},{"key":"2025031409274209300_awae271-B16","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1093\/cid\/ciu773","article-title":"Cerebrospinal fluid inhibitory quotients of antiretroviral drugs in HIV-infected patients are associated with compartmental viral control","volume":"60","author":"Calcagno","year":"2015","journal-title":"Clin Infect Dis"},{"key":"2025031409274209300_awae271-B17","doi-asserted-by":"crossref","first-page":"107200","DOI":"10.1016\/j.ijantimicag.2024.107200","article-title":"INACTION (Italian network of acute HIV infection) study group. 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