Neurocognitive Impairment in HIV-Infected Naive Patients with Advanced Disease: The Role of Virus and Intrathecal Immune Activation

Objective. To investigate intrathecal immune activation parameters and HIV-RNA in HIV-associated neurocognitive disorders (HAND) of advanced naive 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-gamma, TNF-alpha, TGF-beta 1, and TGF-beta 2) and chemokines (MIP-1 alpha, MIP-1 beta, and MCP-1) in plasma and cerebrospinal fluid (CSF) of HIV-infected patients with CD4 <200/mu L. 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-1 beta, 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-1 beta 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 naive 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.