TY - JOUR
T1 - Correlation between cerebrospinal fluid and plasma neurofilament light protein in treated HIV infection
T2 - results from the COBRA study
AU - Alagaratnam, Jasmini
AU - de Francesco, Davide
AU - Zetterberg, Henrik
AU - Heslegrave, Amanda
AU - Toombs, Jamie
AU - Kootstra, Neeltje A.
AU - Underwood, Jonathan
AU - Gisslen, Magnus
AU - Reiss, Peter
AU - Fidler, Sarah
AU - Sabin, Caroline A.
AU - Winston, Alan
N1 - Funding Information: JA has received financial support to attend scientific conferences from MSD, Janssen UK and Gilead Sciences. HZ has served on scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed and CogRx; has given lectures in symposia sponsored by Fujirebio, Alzecure and Biogen; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg (outside submitted work). JU has received honoraria for preparation of educational materials and has served on an advisory board for Gilead Sciences. MG has received research grants from Gilead Sciences and Janssen-Cilag and honoraria as speaker and/or scientific advisor from Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV, Janssen-Cilag and MSD. PR through his institution has received independent scientific grant support from Gilead Sciences, Janssen Pharmaceuticals Inc., Merck & Co and ViiV Healthcare, and has served on scientific advisory boards for Gilead Sciences, ViiV Healthcare, Merck & Co. and Teva pharmaceutical industries, for which honoraria were all paid to his institution. AW has received honoraria or research grants on behalf of Imperial College London or been a consultant or investigator in clinical trials sponsored by Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Janssen-Cilag, Roche and ViiV Healthcare. CAS has received funding for the membership of Data Safety and Monitoring Boards, Advisory Boards and for preparation of educational materials from Gilead Sciences and ViiV Healthcare. For the remaining authors, none were declared. Funding Information: This sub-study is independent research funded by grants awarded by the British HIV Association (BHIVA) and Imperial Health Charity. Funding Information: A Wellcome Trust Multi-User Equipment grant to HZ and AH funded the instrument used for the biomarker measurements. Funding Information: The COBRA study was supported by a European Union’s Seventh Framework Programme grant to the Comorbidity in Relation to AIDS (COBRA) project (FP-7-HEALTH 305,522), National Institute for Health Research (NIHR) Professorship (NIHR-RP-011–048), NIHR Imperial Biomedical Research Centre, the Netherlands Organisation for Health Research and Development (grant number 300020007) & Stichting AIDS Fonds (grant number 2009063), Nuts-Ohra Foundation (grant number 1003–026) and unrestricted scientific grants from: Gilead Sciences, ViiV Healthcare, Janssen Pharmaceutica N.V. Bristol-Myers Squibb (BMS), and Merck & Co to the AGEhIV cohort study, and investigator initiated grants from BMS, Gilead Sciences, Janssen, Merck and ViiV Healthcare to the POPPY cohort study. Publisher Copyright: © 2021, The Author(s).
PY - 2021
Y1 - 2021
N2 - Cerebrospinal fluid (CSF) neurofilament light protein (NfL) is a marker of central nervous system neuro-axonal injury. A novel, ultra-sensitive assay can determine plasma NfL. In untreated people-with-HIV (PWH), CSF and plasma NfL are strongly correlated. We aimed to assess this correlation in PWH on suppressive antiretroviral treatment (ART) and lifestyle-similar HIV-negative individuals enrolled into the COmorBidity in Relation to AIDS (COBRA) study. Differences in paired CSF (sandwich ELISA, UmanDiagnostics) and plasma (Simoa digital immunoassay, Quanterix™) NfL between PWH and HIV-negative participants were tested using Wilcoxon’s test; associations were assessed using Pearson’s correlation. CSF and plasma NfL, standardised to Z-scores, were included as dependent variables in linear regression models to identify factors independently associated with values in PWH and HIV-negative participants. Overall, 132 PWH (all with plasma HIV RNA < 50 copies/mL) and 79 HIV-negative participants were included. Neither CSF (median 570 vs 568 pg/mL, p = 0.37) nor plasma (median 10.7 vs 9.9 pg/mL, p = 0.15) NfL differed significantly between PWH and HIV-negative participants, respectively. CSF and plasma NfL correlated moderately, with no significant difference by HIV status (PWH: rho = 0.52; HIV-negative participants: rho = 0.47, p (interaction) = 0.63). In multivariable regression analysis, higher CSF NfL Z-score was statistically significantly associated with older age and higher CSF protein, and higher plasma NfL Z-score with older age, higher serum creatinine and lower bodyweight. In conclusion, in PWH on ART, the correlation between CSF and plasma NfL is moderate and similar to that observed in lifestyle-similar HIV-negative individuals. Consideration of renal function and bodyweight may be required when utilising plasma NfL.
AB - Cerebrospinal fluid (CSF) neurofilament light protein (NfL) is a marker of central nervous system neuro-axonal injury. A novel, ultra-sensitive assay can determine plasma NfL. In untreated people-with-HIV (PWH), CSF and plasma NfL are strongly correlated. We aimed to assess this correlation in PWH on suppressive antiretroviral treatment (ART) and lifestyle-similar HIV-negative individuals enrolled into the COmorBidity in Relation to AIDS (COBRA) study. Differences in paired CSF (sandwich ELISA, UmanDiagnostics) and plasma (Simoa digital immunoassay, Quanterix™) NfL between PWH and HIV-negative participants were tested using Wilcoxon’s test; associations were assessed using Pearson’s correlation. CSF and plasma NfL, standardised to Z-scores, were included as dependent variables in linear regression models to identify factors independently associated with values in PWH and HIV-negative participants. Overall, 132 PWH (all with plasma HIV RNA < 50 copies/mL) and 79 HIV-negative participants were included. Neither CSF (median 570 vs 568 pg/mL, p = 0.37) nor plasma (median 10.7 vs 9.9 pg/mL, p = 0.15) NfL differed significantly between PWH and HIV-negative participants, respectively. CSF and plasma NfL correlated moderately, with no significant difference by HIV status (PWH: rho = 0.52; HIV-negative participants: rho = 0.47, p (interaction) = 0.63). In multivariable regression analysis, higher CSF NfL Z-score was statistically significantly associated with older age and higher CSF protein, and higher plasma NfL Z-score with older age, higher serum creatinine and lower bodyweight. In conclusion, in PWH on ART, the correlation between CSF and plasma NfL is moderate and similar to that observed in lifestyle-similar HIV-negative individuals. Consideration of renal function and bodyweight may be required when utilising plasma NfL.
KW - Axons
KW - Central nervous system diseases
KW - HIV
KW - HIV-1
KW - Neurofilament proteins
UR - http://www.scopus.com/inward/record.url?scp=85120680486&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s13365-021-01026-3
DO - https://doi.org/10.1007/s13365-021-01026-3
M3 - Article
C2 - 34874540
SN - 1355-0284
JO - JOURNAL OF NEUROVIROLOGY
JF - JOURNAL OF NEUROVIROLOGY
ER -