Assessing the role of peripheral CD8 T cells in neurocognitive impairment in HIV-infected men who have sex with men: data from the MSM Neurocog Study

Abstract

Studies have suggested CD8 lymphocytes may be a possible marker for inflammation, which is believed to be a contributing factor to neurocognitive impairment. Individuals enrolled in the MSM Neurocog Study were analysed. Those with depression, anxiety or mood disorders were excluded. Individuals with neurocognitive impairment were identified using the Brief NeuroCognitive Screen and compared to those with normal scores. CD4 and CD8 T cell values and CD4:CD8 ratios were compared between groups. In all, 144 men, aged 18-50 years, were included in the analysis. Twenty were diagnosed with neurocognitive impairment. We were unable to identify any significant difference between current, nadir or peak CD4 and CD8 counts. CD4:CD8 ratios and CD4:CD8 ratio inversion (<1) were also found to be similar between both groups. However, neurocognitive impairment subjects were 8% more likely to have inversion of CD4:CD8 ratio and higher median peak CD8 cell counts reported compared to non-impaired subjects. Analysis of data from the MSM Neurocog Study, demonstrated trends in peripheral CD8 counts and CD4:CD8 ratios. However, we are unable to demonstrate any significant benefit. Plasma biomarkers of neurocognitive impairment in HIV-infected subjects would be of great benefit over current methods of invasive CSF analysis and technical neuroimaging used in the diagnosis of neurocognitive impairment. Future, prospective, longitudinal work with large numbers of neurocognitive impairment subjects is required to further investigate the role of peripheral CD8 T cells as markers of neurocognitive impairment.

HIV-Associated Neurocognitive Impairment in the Modern ART Era: Are We Close to Discovering Reliable Biomarkers in the Setting of Virological Suppression?

“…Moreover, a significant correlation between CD4/CD8 ratio and T-cell activation (measured by the number of CD4+CD38+HLADR+ T lymphocytes) was found, contributing to the evidence that CD4/CD8 ratio can be considered as a marker of chronic immune activation. A similar analysis was performed in MSM (men who have sex with men) Neurocog Study, in which 200 HIV-infected MSM PWH were screened for NCI and, after excluding people suffering from anxiety, depression or previous diagnosis of mood disorders, 20 were identified as potentially having NCI (Rawson et al, 2015). In this study, no significant difference in current, nadir or peak CD4 and CD8 counts, CD4/CD8 ratios, CD4/CD8 ratio inversion (<1), plasma viral load detectability, and peak plasma viral load were identified between subjects with NCI and the control group.…”

Correlation between CD4/CD8 ratio and neurocognitive performance during early HIV infection

“…Systemic and CSF CD4 and CD8 T‐cells express greater concentration of HLA‐DR, a marker for T‐cell activation, among chronically HIV‐infected individuals with HAND as compared with those without HAND [33]. Moreover, chronically HIV‐infected individuals with symptomatic HAND display higher rates of inverted CD4/CD8 ratio than either unimpaired individuals or individuals with asymptomatic neurocognitive disorders, the latter defined by at least two impaired cognitive domains without any impact on daily living [34, 35]. Independent of viral replication and suppression, longitudinal decline in the ratio is associated with neurocognitive deterioration [36].…”

Virologically suppressed patients with asymptomatic and symptomatic HIV‐associated neurocognitive disorders do not display the same pattern of immune activation

“…Immune activation could thus be responsible for neurological disorders, but few studies have investigated this possibility .…”