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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
- Article/chapterEnglish2021
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LIBRIS-ID:oai:gup.ub.gu.se/309556
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https://gup.ub.gu.se/publication/309556URI
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https://doi.org/10.1016/j.jve.2021.100056DOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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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.
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Stohr, W.
(author)
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Toombs, J.
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Heslegrave, A.
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Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xzethe
(author)
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Gisslén, Magnus,1962Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine(Swepub:gu)xgissm
(author)
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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.
(author)
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Fidler, S.
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River Trial Study Grp, River Trial Study Grp
(author)
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Göteborgs universitetInstitutionen för neurovetenskap och fysiologi
(creator_code:org_t)
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In:Journal of Virus Eradication: Elsevier BV7:32055-6640
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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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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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- MEDICAL AND HEALTH SCIENCES
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University of Gothenburg