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CCR2 on Peripheral Blood CD14+CD16+ Monocytes Correlates with Neuronal Damage, HIV-Associated Neurocognitive Disorders, and Peripheral HIV DNA: reseeding of CNS reservoirs?


HIV-associated neurocognitive disorders (HAND) occur in ~50% of HIV infected individuals despite combined antiretroviral therapy. Transmigration into the CNS of CD14+CD16+ monocytes, particularly those that are HIV infected and express increased surface chemokine receptor CCR2, contributes to neuroinflammation and HAND. To examine whether in HIV infected individuals CCR2 on CD14+CD16+ monocytes serves as a potential peripheral blood biomarker of HAND, we examined a cohort of 45 HIV infected people. We correlated CCR2 on CD14+CD16+ monocytes with cognitive status, proton magnetic resonance spectroscopy (1H-MRS) measured neurometabolite levels, and peripheral blood mononuclear cell (PBMC) HIV DNA copies. We determined that CCR2 was increased specifically on CD14+CD16+ monocytes from people with HAND (median [interquartile range (IQR)]) (63.3 [51.6, 79.0]), compared to those who were not cognitively impaired (38.8 [26.7, 56.4]) or those with neuropsychological impairment due to causes other than HIV (39.8 [30.2, 46.5]). CCR2 was associated with neuronal damage, based on the inverse correlation of CCR2 on CD14+CD16+ monocytes with total N-Acetyl Aspartate (tNAA)/total Creatine (tCr) (r2 = 0.348, p = 0.01) and Glutamine-Glutamate (Glx)/tCr (r2 = 0.356, p = 0.01) in the right and left caudate nucleus, respectively. CCR2 on CD14+CD16+ monocytes also correlated with PBMC HIV DNA copies (ρ = 0.618, p = 0.02) that has previously been associated with HAND. These findings suggest that CCR2 on CD14+CD16+ monocytes may be a peripheral blood biomarker of HAND, indicative of increased HIV infected CD14+CD16+ monocyte entry into the CNS that possibly increases the macrophage viral reservoir and contributes to HAND.

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The authors thank MHBB staff and patients who generously contributed their time to the study. This study was funded by National Institutes of Health U24MH100931 (MHBB) (S.M.), R01MH075679 (J.W.B.), R21MH102113-01A1 (J.W.B), R01MH090958 (J.W.B.), R01MH112391 (T.M.C., J.W.B.), R01NS077869 (J.E.C), R01AI127142 (J.E.C.), P30AI124414 (ERC CFAR) (M.V., R.L-R., T.M.C., J.W.B.), Mount Sinai Institute for NeuroAIDS Disparities (R25 MH080663) (R.L-R.), MSTP Training Grant at Albert Einstein College of Medicine (5T32GM007288) (R.L-R.), TL1TR001072 (Einstein-Montefiore CTSA) (M.V.), pilot research grant Icahn School of Medicine Brain Imaging Center (S.M.), National MS Society RG 5120A3/1 (M.I.), and eCLIPSE fellowship (M.V.), Burroughs Wellcome Foundation Grant program “Unifying Population and Laboratory Science”.

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Correspondence to Susan Morgello or Joan W. Berman.

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Veenstra, M., Byrd, D.A., Inglese, M. et al. CCR2 on Peripheral Blood CD14+CD16+ Monocytes Correlates with Neuronal Damage, HIV-Associated Neurocognitive Disorders, and Peripheral HIV DNA: reseeding of CNS reservoirs?. J Neuroimmune Pharmacol 14, 120–133 (2019). https://doi.org/10.1007/s11481-018-9792-7

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  • HAND
  • CD14+CD16+ Monocytes
  • CCR2
  • HIV
  • ddPCR