Plasma CXCL10 correlates with HAND in HIV-infected women

Abstract

HIV-associated neurocognitive disorder (HAND) is characterized by chronic immune activation. We aimed to identify biomarkers associated with HAND and to investigate their association with cognitive function and sex, in a homogenous cohort of HIV-infected (HIV+) young adults, parenterally infected during early childhood. One hundred forty-four HIV+ Romanian participants (51% women) without major confounders underwent standardized neurocognitive and medical evaluation in a cross-sectional study. IFN-γ, IL-1β, IL-6, CCL2, CXCL8, CXCL10, and TNF-α were measured in plasma in all participants and in cerebrospinal fluid (CSF) in a subgroup of 56 study participants. Biomarkers were compared with neurocognitive outcomes, and the influence of sex and HIV disease biomarkers was assessed. In this cohort of young adults (median age of 24 years), the rate of neurocognitive impairment (NCI) was 36.1%. Median current CD4+ count was 479 cells/mm3 and 36.8% had detectable plasma viral load. Women had better HIV-associated overall status. In plasma, controlling for sex, higher levels of IL-6 and TNF-α were associated with NCI (p < 0.05). Plasma CXCL10 showed a significant interaction with sex (p = 0.02); higher values were associated with NCI in women only (p = 0.02). Individuals with undetectable viral load had significantly lower plasma CXCL10 (p < 0.001) and CCL2 (p = 0.02) levels, and CSF CXCL10 (p = 0.01), IL-6 (p = 0.04), and TNF-α (p = 0.04) levels. NCI in young men and women living with HIV was associated with higher IL-6 and TNF-α in plasma, but not in the CSF. CXCL10 was identified as a biomarker of NCI specifically in women with chronic HIV infection.

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Acknowledgements

The authors would like to thank all participants in the study; Terence Hendrix from the HIV Neurobehavioral Research Center in San Diego for neuropsychological training and study coordination, Anca Luca and Adrian Luca, psychologists, for their help with neuropsychological testing, Roxana Radoi, MD, for neuromedical evaluation, and Gratiela Tardei, MD, PhD, for the clinical laboratory assessments.

Funding

This work was supported by 1R01MH094159 and P30MH62512 from National Institute of Mental Health (NIMH).

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R.B. contributed to the study design and conception and interpretation of the data and drafted the manuscript. L.E., T.D.M., C.L.A., and S.M.R. contributed to the study design and conception, to the interpretation of the data, and edited the manuscript. A.U. performed the statistical analysis, contributed to drafting, and edited the manuscript. R.B., L.E., and A.B.T. contributed to patient recruitment and testing and assisted with the collection of data. C.C.D. and B.S. helped with biomarker level determination and interpretation of the data. C.C.D. and S.L, A.T. helped with data interpretation and edited the manuscript. All authors read and approved the final manuscript.

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Correspondence to R. Burlacu.

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Conflict of interest

R.B., A.U., A.B.T., A.T., S.M.R. and C. C. D. report grants from National Institute of Mental Health (NIMH), during the conduct of the study. L.E. reports grants from National Institute of Mental Health (NIMH), during the conduct of the study; personal fees and non-financial support from Abbvie, personal fees from Johnson & Johnson, personal fees from Merck Sharp & Dohme and personal fees from Bristol-Myers Squibb, outside the submitted work. C. L. A., T.D.M., B.S. and S. L. have nothing to disclose.

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Burlacu, R., Umlauf, A., Marcotte, T.D. et al. Plasma CXCL10 correlates with HAND in HIV-infected women. J. Neurovirol. 26, 23–31 (2020). https://doi.org/10.1007/s13365-019-00785-4

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Keywords

  • HIV women
  • CXCL-10
  • Neurocognitive
  • HIV inflammation
  • Young adults