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No evidence of neuronal damage as measured by neurofilament light chain in a HIV cure study utilising a kick-and-kill approach

Alagaratnam, Jasmini, Stöhr, Wolfgang, Toombs, Jamie, Heslegrave, Amanda, Zetterberg, Henrik, Gisslén, Magnus, Pett, Sarah, Nelson, Mark, Clarke, Amanda, Nwokolo, Nneka, Johnson, Margaret A., Khan, Maryam, Hanke, Tomas, Kopycinski, Jakub, Dorrell, Lucy, Fox, Julie, Kinloch, Sabine, Underwood, Jonathan, Pace, Matthew, Frater, John, Winston, Alan and Fidler, Sarah 2021. No evidence of neuronal damage as measured by neurofilament light chain in a HIV cure study utilising a kick-and-kill approach. Journal of Virus Eradication 7 (3) , 100056. 10.1016/j.jve.2021.100056

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Abstract

Objective HIV-remission strategies including kick-and-kill could induce viral transcription and immune-activation in the central nervous system, potentially causing neuronal injury. We investigated the impact of kick-and-kill on plasma neurofilament light (NfL), a marker of neuro-axonal injury, in RIVER trial participants commencing antiretroviral treatment (ART) during primary infection and randomly allocated to ART-alone or kick-and-kill (ART + vaccination + vorinostat (ART + V + V)). Design Sub-study measuring serial plasma NfL concentrations. Methods Plasma NfL (using Simoa digital immunoassay), plasma HIV-1 RNA (using single-copy assay) and total HIV-1 DNA (using quantitative polymerase chain reaction in peripheral CD4+ T-cells) were measured at randomisation (following ≥22 weeks ART), week 12 (on final intervention day in ART + V + V) and week 18 post-randomisation. HIV-specific T-cells were quantified by intracellular cytokine staining at randomisation and week 12. Differences in plasma NfL longitudinally and by study arm were analysed using mixed models and Student's t-test. Associations with plasma NfL were assessed using linear regression and rank statistics. Results At randomisation, 58 male participants had median age 32 years and CD4+ count 696 cells/μL. No significant difference in plasma NfL was seen longitudinally and by study arm, with median plasma NfL (pg/mL) in ART-only vs ART + V + V: 7.4 vs 6.4, p = 0.16 (randomisation), 8.0 vs 6.9, p = 0.22 (week 12) and 7.1 vs 6.8, p = 0.74 (week 18). Plasma NfL did not significantly correlate with plasma HIV-1 RNA and total HIV-1 DNA concentration in peripheral CD4+ T-cells at any timepoint. While higher HIV-specific T-cell responses were seen at week 12 in ART + V + V, there were no significant correlations with plasma NfL. In multivariate analysis, higher plasma NfL was associated with older age, higher CD8+ count and lower body mass index. Conclusions Despite evidence of vaccine-induced HIV-specific T-cell responses, we observed no evidence of increased neuro-axonal injury using plasma NfL as a biomarker up to 18 weeks following kick-and-kill, compared with ART-only.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
ISSN: 2055-6640
Date of First Compliant Deposit: 23 September 2021
Date of Acceptance: 8 September 2021
Last Modified: 28 Sep 2021 11:30
URI: https://orca.cardiff.ac.uk/id/eprint/144368

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