Serum and CSF biomarkers in asymptomatic patients during primary HIV infection: a randomized study.

Autor:	Calcagno A; Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, 10149 Turin, Italy., Cusato J; Laboratory of Clinical Pharmacology and Pharmacogenetics, University of Turin, 10149 Turin, Italy., Cinque P; Infectious Diseases Unit, IRCCS Ospedale San Raffaele, 20132 Milan, Italy., Marchetti G; Clinic of Infectious Diseases, Department of Health Sciences, ASST Santi Paolo e Carlo, University of Milan, 20142 Milan, Italy.; School of Medicine and Surgery, University of Milan, 20122 Milan, Italy., Bernasconi D; Bicocca Bioinformatics Biostatistics and Bioimaging Centre - B4 School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy.; Department of Clinical Research and Innovation, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy., Trunfio M; Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, 10149 Turin, Italy.; HIV Neurobehavioral Research Program, Department of Psychiatry, University of California, UCSD, La Jolla, CA 92093-0021, USA., Bruzzesi E; Infectious Diseases Unit, IRCCS Ospedale San Raffaele, 20132 Milan, Italy., Rusconi S; School of Medicine and Surgery, University of Milan, 20122 Milan, Italy.; SC Malattie Infettive, Ospedale di Legnano, ASST Ovest Milanese, 20025 Legnano, Italy., Gabrieli A; Dipartimento di Scienze Biomediche e Cliniche (DIBIC), 20157 Milan, Italy., Muscatello A; Infectious Diseases Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy., Antinori A; Clinical Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, 00149 Rome, Italy., Ripamonti D; Infectious Disease Unit, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy., Gulminetti R; Division of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy., Antonucci M; SCDU Infectious Diseases, Amedeo di Savoia Hospital, ASL Città di Torino, 10149 Turin, Italy., Nozza S; Infectious Diseases Unit, IRCCS Ospedale San Raffaele, 20132 Milan, Italy.
Jazyk:	angličtina
Zdroj:	Brain : a journal of neurology [Brain] 2024 Nov 04; Vol. 147 (11), pp. 3742-3750.
DOI:	10.1093/brain/awae271
Abstrakt:	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. 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 pg/ml if 5-18 years, 10 pg/ml if 18-51 years, 15 pg/ml if 51-61 years, 20 pg/ml if 61-70 years and 35 pg/ml if >70 years). 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 (ρ = 0.692, P = 0.009), GFAP (ρ = 0.659, P = 0.014) and brain-derived neurotrophic factor (ρ = 0.587, P = 0.045). Serum (ρ = 0.560, P = 0.046) and CSF NFL (ρ = 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). 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. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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