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

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)). Sub-study measuring serial plasma NfL concentrations. 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 At randomisation, 58 male participants had median age 32 years and CD4 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.

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© 2021 The Authors.

Déclaration de conflit d'intérêts

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Jasmini Alagaratnam has received support to attend scientific conferences from MSD and Gilead Sciences. Henrik Zetterberg has served at 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). Henrik Zetterberg is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931 and #ALFGBG-717531)) and the UK Dementia Research Institute at UCL. Magnus Gisslen has received research grants from Gilead Sciences and Janssen-Cilag and honoraria as speaker and/or scientific advisor from Amgen, Bionor, Bristol-Myers Squibb, Gilead Sciences, GSK group of companies/ViiV, Janssen-Cilag, and MSD. Sarah Pett has received funding and research grants on behalf of UCL from Gilead Sciences, ViiV Healthcare, Janssen-Cilag, NIH, MRC, and EDCTP. Funding in support of her salary came through MRC core funding (MR_UU_12023). Amanda Clarke has received honoraria and conference attendance support from ViiV and Gilead sciences and is an investigator in clinical trials sponsored by Gilead, ViiV/GSK & Merck. Sabine Kinloch has received consultant honoraria from Janssen and Viiv. Jonathan Underwood has received honoraria for preparation of educational materials and has served on an advisory board for Gilead Sciences. Alan Winston 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, GSK group of companies, Janssen-Cilag, Roche and ViiV Healthcare. Sarah Fidler received funding and research grants to Imperial College London from the National Institutes of Health (NIH), Bill & Melinda Gates Foundation (BMGF) and Medical Research Council (MRC). For the remaining authors, none were declared.