Neurocognitive impairment in HIV-infected naïve patients with advanced disease: the role of virus and intrathecal immune activation

Abstract

Objective: To investigate intrathecal immune activation parameters and HIV-RNA in HIV-associated neurocognitive disorders (HAND) of advanced naïve HIV-infected patients and to evaluate their dynamics before and after initiation of antiretroviral therapy (ART).

Methods: Cross-sectional and longitudinal analysis of HIV RNA, proinflammatory cytokines (IL-6, IL-10, INF-γ, TNF-α, TGF-β1, and TGF-β2) and chemokines (MIP-1α, MIP-1β, and MCP-1) in plasma and cerebrospinal fluid (CSF) of HIV-infected patients with CD4 <200/μL.

Results: HAND was diagnosed at baseline in 6/12 patients. Baseline CSF HIV-RNA was comparable in patients with or without HAND, whereas CSF concentration of IL-6 and MIP-1β, proinflammatory cytokines, was increased in HAND patients. CSF evaluation at 12 weeks was available in 10/12 cases. ART greatly reduced HIV-RNA in all patients. Nevertheless, IL-6 and MIP-1β remained elevated after 12 weeks of therapy in HAND patients, in whom CSF HIV RNA decay was slower than the plasmatic one as well.

Conclusion: Immune activation, as indicated by inflammatory cytokines, but not higher levels of HIV-RNA is observed in advanced naïve HIV-infected patients with HAND. In HAND patients, ART introduction resulted in a less rapid clearance of CSF viremia compared to plasma and no modifications of intratechal immune activation.

Figure 1

Representation of CSF HIV-RNA dynamics (a), difference in HIV-RNA levels between plasma and CSF (Δ) (b) and cytokines (IL-6, MIP-1β) concentrations at baseline. At baseline and after 12 weeks of ART, CSF HIV-RNA was not different between HAND patients and controls (Figure 1(a)). Difference in HIV-RNA levels between plasma and CSF (Δ), both at baseline and at week 12, showed a value > 0.5 log copies/mL in 3/4 patients in the HAND group and in 1/5 in the control group, reflecting a slower decrease in HIV-RNA level in CSF as compared to plasma in HAND patients (Figure 1(b)). At baseline concentration of MIP-1b and IL-6 in CSF, there was a difference between the two groups of patients (Figure 1(c)).