CCR2 on Peripheral Blood CD14CD16 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 CD14CD16 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 CD14CD16 monocytes serves as a potential peripheral blood biomarker of HAND, we examined a cohort of 45 HIV infected people. We correlated CCR2 on CD14CD16 monocytes with cognitive status, proton magnetic resonance spectroscopy (H-MRS) measured neurometabolite levels, and peripheral blood mononuclear cell (PBMC) HIV DNA copies. We determined that CCR2 was increased specifically on CD14CD16 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 CD14CD16 monocytes with total N-Acetyl Aspartate (tNAA)/total Creatine (tCr) (r = 0.348, p = 0.01) and Glutamine-Glutamate (Glx)/tCr (r = 0.356, p = 0.01) in the right and left caudate nucleus, respectively. CCR2 on CD14CD16 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 CD14CD16 monocytes may be a peripheral blood biomarker of HAND, indicative of increased HIV infected CD14CD16 monocyte entry into the CNS that possibly increases the macrophage viral reservoir and contributes to HAND.