117. Insight into the role of CD8 T cells in HIV-associated neurocognitive impairment

Previous studies of HIV-associated neurocognitive disease (HAND) have focused on the role of monocytes/macrophages. Having observed that high CD8 levels are a risk factor for HAND and hypothesizing that cerebrospinal fluid (CSF) could be a portal of entry for activated CD8 T-cells, we investigated cytokine responses by CSF T-cells. HIV+ participants with and without HAND were treated with CNS-penetrating anti-retroviral agents. CSF cells and PBMCs were harvested before treatment and at 6 and 16 weeks post-treatment and assessed for intracellular expression of IL-2, IFNg and TNFa, in response to HIV antigens. Data were examined both longitudinally (16 subjects with 3 visits) and cross-sectionally (30 subjects, total 59 visits). Overall, CD4 and CD8 T-cells in the CSF were more likely to make all three cytokines than CD4 and CD8 T-cells in blood. Impairment was associated with higher levels of constitutive and HIV-induced IFNg (p = .04) and TNFa (p = .05) expression by CD8 T-cells in the CSF. While higher levels of HIV RNA in CSF suppressed CD8 cytokine expression in unimpaired subjects, impaired subjects persisted with high cytokine expression regardless of RNA levels (p = .04). In addition to identifying a novel mechanism of HIV pathogenesis, these findings validate viral suppression in both CSF and the periphery as an important treatment goal for HAND, but also suggest that modulation of the CD8 T-cell response may be required.