Loss of CCR2 expressing non-classical monocytes are associated with cognitive impairment in antiretroviral therapy-naïve HIV-infected Thais

- Monocyte HIV DNA correlates with HAND, which persists despite cART.
- Monocyte subset characterization in the context of HAND remains incomplete.
- Lower CCR2+ non-classical monocyte number associated with worse NPZ testing.
- CCR2+ non-classical monocyte count inversely correlated with neopterin and TNF-α.
- Loss of CCR2+ non-classical monocytes may serve as a biomarker for HAND.

HIV DNA in monocytes has been linked to HIV-associated neurocognitive disorders (HAND), however, characterization of monocyte subsets associated with HAND remains unclear. We completed a prospective study of antiretroviral therapy-naïve, HIV-infected Thais, with varying degrees of cognitive impairment, compared to HIV-uninfected controls. Monocyte subsets' CCR2, CCR5 and CD163 expression were profiled and inflammatory markers in plasma and cerebrospinal fluid (CSF), measured. Lower numbers of CCR2+non-classical monocytes were associated with worse neuropsychological test performance (r = 0.43, p = 0.024). CCR2+non-classical monocyte count inversely correlated with CSF neopterin (r = − 0.43, p = 0.035) and plasma TNF-α levels (r = − 0.40, p = 0.041). These data benchmark CCR2+non-classical monocytes as an independent index of cognitive impairment.

Lower numbers of CCR2 expressing non-classical monocytes (CCR2+Mono3lo) correlated with worse neuropsychological test performance. These data highlight a new promising cellular biomarker of neurocognitive disease.110