4.3 Article

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

Journal

JOURNAL OF NEUROIMMUNOLOGY
Volume 353, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.jneuroim.2021.577493

Keywords

HIV; Central nervous system; Cerebrospinal fluid; Chemokine CXCL10

Funding

  1. National Institutes of Health [R21 MH085610, R01 MH058076, R01 MH107345, K23 MH095679, R21 MH118092, R01 AG062387, K24 MH097673]

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The study found that CSF CXCL10 concentrations reflect low-level HIV CNS persistence despite virologic suppression on ART, which may be a promising biomarker for evaluating HIV eradication therapies targeting the CNS.
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.

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