TY - JOUR
T1 - Higher Levels of Cerebrospinal Fluid and Plasma Neurofilament Light in Human Immunodeficiency Virus-Associated Distal Sensory Polyneuropathy
AU - Ellis, Ronald J.
AU - Chenna, Ahmed
AU - Lie, Yolanda
AU - Curanovic, Dusica
AU - Winslow, John
AU - Tang, Bin
AU - Marra, Christina M.
AU - Rubin, Leah H.
AU - Clifford, David B.
AU - McCutchan, J. Allen
AU - Gelman, Benjamin B.
AU - Robinson-Papp, Jessica
AU - Petropoulos, Christos J.
AU - Letendre, Scott L.
N1 - Funding Information:
Acknowledgments. The CNS HIV Anti-Retroviral Therapy Effects Research was supported by awards N01 MH22005, HHSN271201000036C, HHSN27120100003°C, and R01 MH107345 from the National Institutes of Health.
Funding Information:
Financial support. This work was supported by the National Institutes of Health (grant numbers R01MH107345 to R. K. H. and P30MH62512 to R.K. H.). B, B. G. reports support from NIH (grant number N01 MH22005). L. H. R. reports support from NIMH. J. W., Y. L., D. C., and C. J. P. reports support from Monogram Biosciences, a Labcorp specialty testing group (as employee).
Funding Information:
The HIV Neurobehavioral Research Center (HNRC) is supported by Center award P30MH062512 from NIMH. The San Diego HIV Neurobehavioral Research Center [HNRC] group is affiliated with the University of California, San Diego, the Naval Hospital, San Diego, and the Veterans Affairs San Diego Healthcare System, and includes: Director: Robert K. Heaton, PhD, Co-Director: Igor Grant, MD; Associate Directors: J. Hampton Atkinson, MD, Ronald J. Ellis, MD, PhD, and Scott Letendre, MD; Center Manager: Jennifer Iudicello, PhD; Donald Franklin Jr.; Melanie Sherman; NeuroAssessment Core: Ronald J. Ellis, MD, PhD (PI), Scott Letendre, MD, Thomas D. Marcotte, PhD, Christine Fennema-Notestine, PhD, Debra Rosario, MPH, Matthew Dawson; NeuroBiology Core: Cristian Achim, MD, PhD (PI), Ana Sanchez, PhD, Adam Fields, PhD; NeuroGerm Core: Sara Gianella Weibel, MD (PI), David M. Smith, MD, Rob Knight, PhD, Scott Peterson, PhD; Developmental Core: Scott Letendre, MD (PI), J. Allen McCutchan; Participant Accrual and Retention Unit: J. Hampton Atkinson, MD (PI) Susan Little, MD, Jennifer Marquie-Beck, MPH; Data Management and Information Systems Unit: Lucila Ohno-Machado, PhD (PI), Clint Cushman; Statistics Unit: Ian Abramson, PhD (PI), Florin Vaida, PhD (Co-PI), Anya Umlauf, MS, Bin Tang, MS.
Publisher Copyright:
© The Author(s) 2022.
PY - 2023/3/15
Y1 - 2023/3/15
N2 - Background. Neurofilament light (NFL) chain concentrations, reflecting axonal damage, are seen in several polyneuropathies but have not been studied in human immunodeficiency virus (HIV) distal sensory polyneuropathy (DSP). We evaluated NFL in cerebrospinal fluid (CSF) and plasma in relation to DSP in people with HIV (PWH) from 2 independent cohorts and in people without HIV (PWoH). Methods. Cohort 1 consisted of PWH from the CHARTER Study. Cohort 2 consisted of PWH and PWoH from the HIV Neurobehavioral Research Center (HNRC). We evaluated DSP signs and symptoms in both cohorts. Immunoassays measured NFL in CSF for all and for plasma as well in Cohort 2. Results. Cohort 1 consisted of 111 PWH, mean ± SD age 56.8 ± 8.32 years, 15.3% female, 38.7% Black, 49.6% White, current CD4+ T-cells (median, interquartile range [IQR]) 532/µL (295, 785), 83.5% with plasma HIV RNA ≤50 copies/mL. Cohort 2 consisted of 233 PWH of similar demographics to PWH in Cohort 1 but also 51 PWoH, together age 58.4 ± 6.68 years, 41.2% female, 18.0% Black, Hispanic, non-Hispanic White 52.0%, 6.00% White. In both cohorts of PWH, CSF and plasma NFL were significantly higher in both PWH with DSP signs. Findings were similar, albeit not significant, for PWoH. The observed relationships were not explained by confounds. Conclusions. Both plasma and CSF NFL were elevated in PWH and PWoH with DSP. The convergence of our findings with others demonstrates that NFL is a reliable biomarker reflecting peripheral nerve injury. Biomarkers such as NFL might provide, validate, and optimize clinical trials of neuroregenerative strategies in HIV DSP.
AB - Background. Neurofilament light (NFL) chain concentrations, reflecting axonal damage, are seen in several polyneuropathies but have not been studied in human immunodeficiency virus (HIV) distal sensory polyneuropathy (DSP). We evaluated NFL in cerebrospinal fluid (CSF) and plasma in relation to DSP in people with HIV (PWH) from 2 independent cohorts and in people without HIV (PWoH). Methods. Cohort 1 consisted of PWH from the CHARTER Study. Cohort 2 consisted of PWH and PWoH from the HIV Neurobehavioral Research Center (HNRC). We evaluated DSP signs and symptoms in both cohorts. Immunoassays measured NFL in CSF for all and for plasma as well in Cohort 2. Results. Cohort 1 consisted of 111 PWH, mean ± SD age 56.8 ± 8.32 years, 15.3% female, 38.7% Black, 49.6% White, current CD4+ T-cells (median, interquartile range [IQR]) 532/µL (295, 785), 83.5% with plasma HIV RNA ≤50 copies/mL. Cohort 2 consisted of 233 PWH of similar demographics to PWH in Cohort 1 but also 51 PWoH, together age 58.4 ± 6.68 years, 41.2% female, 18.0% Black, Hispanic, non-Hispanic White 52.0%, 6.00% White. In both cohorts of PWH, CSF and plasma NFL were significantly higher in both PWH with DSP signs. Findings were similar, albeit not significant, for PWoH. The observed relationships were not explained by confounds. Conclusions. Both plasma and CSF NFL were elevated in PWH and PWoH with DSP. The convergence of our findings with others demonstrates that NFL is a reliable biomarker reflecting peripheral nerve injury. Biomarkers such as NFL might provide, validate, and optimize clinical trials of neuroregenerative strategies in HIV DSP.
KW - HIV
KW - biomarker
KW - cerebrospinal fluid
KW - neurofilament light
KW - polyneuropathy
UR - http://www.scopus.com/inward/record.url?scp=85150751838&partnerID=8YFLogxK
U2 - 10.1093/cid/ciac851
DO - 10.1093/cid/ciac851
M3 - Article
C2 - 36310512
AN - SCOPUS:85150751838
SN - 1058-4838
VL - 76
SP - 1103
EP - 1109
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 6
ER -