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No evidence of neur...
No evidence of neuronal damage as measured by neurofilament light chain in a HIV cure study utilising a kick-and-kill approach
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Alagaratnam, J. (author)
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Stohr, W. (author)
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Toombs, J. (author)
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Heslegrave, A. (author)
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- Zetterberg, Henrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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- Gisslén, Magnus, 1962 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine
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Pett, S. (author)
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Nelson, M. (author)
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Clarkem, A. (author)
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Nwokolo, N. (author)
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Johnson, M. A. (author)
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Khan, M. (author)
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Hanke, T. (author)
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Kopycinski, J. (author)
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Dorrell, L. (author)
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Fox, J. (author)
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Kinloch, S. (author)
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Underwood, J. (author)
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Pace, M. (author)
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Fratert, J. (author)
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Winston, A. (author)
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Fidler, S. (author)
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River Trial Study Grp, River Trial Study Grp (author)
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(creator_code:org_t)
- Elsevier BV, 2021
- 2021
- English.
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In: Journal of Virus Eradication. - : Elsevier BV. - 2055-6640. ; 7:3
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Abstract
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- 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/mu L. 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Keyword
- Neurofilament light chain protein
- Neuro-axonal injury
- Vorinostat
- HIV-1 therapeutic vaccination
- HIV-1 remission approach
- Kick and kill
- viral reservoirs
- infection
- latency
- cells
- reactivation
- strategies
- provides
- protein
- marker
- shock
- Immunology
- Infectious Diseases
- Virology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Alagaratnam, J.
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Stohr, W.
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Toombs, J.
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Heslegrave, A.
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Zetterberg, Henr ...
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Gisslén, Magnus, ...
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show more...
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Pett, S.
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Nelson, M.
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Clarkem, A.
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Nwokolo, N.
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Johnson, M. A.
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Khan, M.
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Hanke, T.
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Kopycinski, J.
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Dorrell, L.
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Fox, J.
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Kinloch, S.
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Underwood, J.
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Pace, M.
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Fratert, J.
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Winston, A.
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Fidler, S.
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River Trial Stud ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Infectious Medic ...
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Journal of Virus ...
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University of Gothenburg