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. 2021 Apr 15:353:577493.
doi: 10.1016/j.jneuroim.2021.577493. Epub 2021 Jan 21.

Cerebrospinal fluid CXCL10 is associated with the presence of low level CSF HIV during suppressive antiretroviral therapy

Albert M Anderson  1 , Suprateek Kundu  2 , Bin Tang  3 , Florin Vaida  3 , Oluwakemi Okwuegbuna  3 , Daniel McClernon  4 , Mariana Cherner  3 , Reena Deutsch  3 , Debra Cookson  3 , Melanie Crescini  3 , Igor Grant  3 , Henrik Zetterberg  5 , Kaj Blennow  6 , Magnus Gisslen  7 , Ronald J Ellis  8 , Scott L Letendre  9
Affiliations

Cerebrospinal fluid CXCL10 is associated with the presence of low level CSF HIV during suppressive antiretroviral therapy

Albert M Anderson et al. J Neuroimmunol. .

Abstract

Surrogate markers of HIV central nervous system (CNS) persistence are needed because direct HIV measurements from the CNS require specialized protocols and are not always detectable or quantifiable. We analyzed paired plasma and CSF samples from people with HIV (PWH) on suppressive therapy (ART) with a validated HIV single copy RNA assay. Two potential markers of CNS persistence were measured (CXCL10 and sCD30). We then examined associations with CSF HIV RNA positivity in univariable and multivariable analyses. Among 66 individuals, 18.2% had detectable CSF HIV. Individuals who had detectable HIV in CSF had higher CSF CXCL10 concentrations (median 514 pg/ml versus median 317 pg/ml, p = 0.019), but did not have significantly different CSF sCD30 concentrations (median 7.5 ng/ml versus median 7.6 ng/ml, p = 0.78). In the multiple logistic analysis, both higher CSF CXCL10 (p = 0.038) and plasma HIV detectability (p = 0.035) were significantly associated with detectable CSF HIV. Both sCD30 and CXCL10 correlated positively with NfL and NSE, two neuronal markers. This study demonstrates that CSF CXCL10 concentrations reflect low level HIV CNS persistence despite virologic suppression on ART. Given that it is readily detectable and quantifiable, this chemokine may be a promising biomarker to evaluate HIV eradication therapies that target the CNS.

Keywords: Central nervous system; Cerebrospinal fluid; Chemokine CXCL10; HIV.

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Conflict of interest statement

A Anderson reports no conflicts

S Kundu reports no conflicts

B Tang reports no conflicts

F Vaida reports no conflicts

O Okwuegbuna reports no conflicts

D McClernon reports no conflicts

M Cherner reports no conflicts

R Deutsch reports no conflicts

D Cookson reports no conflicts

M Crescini reports no conflicts

I Grant reports no conflicts

H Zetterberg reports no conflicts

K Blennow reports no conflicts

M Gisslen reports no conflicts R Ellis reports no conflicts

S Letendre reports no conflicts

Figures

Fig. 1.
Fig. 1.
CSF CXCL10 concentration in participants with detectable CSF HIV RNA (CSFHIV+) versus with undetectable CSF HIV RNA (CSFHIVneg)
Fig. 2.
Fig. 2.
CSF sCD30 concentration in participants with detectable CSF HIV RNA (CSFHIV+) versus with undetectable CSF HIV RNA (CSFHIVneg)
Figure 3
Figure 3
Correlation matrices with density ellipses for the four CSF biomarkers: CXCL10, sCD30, NFL, and NSE. Units are in picograms/milliliter except for sCD30 which is nanograms/milliliter. Spearman’s rho and p values are: NFL to NSE: rho=0.31, p= 0.011; sCD30 to CXCL10: rho=0.23, p=0.067; CXCL10 to NFL: rho=0.29, p=0.02; CXCL10 to NSE: rho=0.26, p=0.033; sCD30 to NFL: rho=0.34, p=0.005; and sCD30 to NSE rho=0.25, p=0.048.
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