Hindawi Publishing Corporation Clinical and Developmental Immunology Volume 2012, Article ID 467154, 5 pages doi:10.1155/2012/467154 Clinical Study Neurocognitive Impairment in HIV-Infected Na¨ ıve Patients with Advanced Disease: The Role of Virus and Intrathecal Immune Activation Monica Airoldi, 1 Alessandra Bandera, 1 Daria Trabattoni, 2 Benedetta Tagliabue, 3 Beatrice Arosio, 4 Alessandro Soria, 1 Veronica Rainone, 2 Giuseppe Lapadula, 1 Giorgio Annoni, 3 Mario Clerici, 2, 5 and Andrea Gori 1 1 Division of Infectious Diseases, Department of Internal Medicine, “San Gerardo” Hospital, University of Milan-Bicocca, 20900 Monza, Italy 2 LITA VIALBA, University of Milan, 20157 Milan, Italy 3 Department of Clinical Medicine and Prevention, University of Milan-Bicocca, SCC Geriatrics, 20900 Monza, Italy 4 Geriatric Unit, University of Milan, Fondazione C` a Granda, IRCCS Ospedale Maggiore Policlinico, 20122 Milan, Italy 5 Don C. Gnocchi Foundation, IRCCS, 20148 Milan, Italy Correspondence should be addressed to Alessandra Bandera, a.bandera@hsgerardo.org Received 14 October 2011; Revised 10 January 2012; Accepted 10 January 2012 Academic Editor: Carlo Torti Copyright © 2012 Monica Airoldi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective. To investigate intrathecal immune activation parameters and HIV-RNA in HIV-associated neurocognitive disorders (HAND) of advanced na¨ ıve 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 na¨ ıve 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. 1. Introduction HIV can cause a wide range of neurocognitive complications which were recently regrouped under the acronym of HAND, that is, HIV-associated neurocognitive disorders [1]. HAND reflects a spectrum of neurologic diseases ranging from subclinical neuropsychological impairment, such as as- ymptomatic neurocognitive impairment (ANI) or mild neu- rocognitive disorder (MND), to clinically evident HIV-asso- ciated dementia (HAD) [2]. Following the introduction of antiretroviral therapy (ART), the HAND profile has changed. Indeed, widespread use of ART has decreased the prevalence of HIV-associated dementia (HAD), but the prevalence of milder forms of HIV-associated neurocognitive disorders (HAND) has remained stable or increased among both treat- ed and untreated individuals [3–5]. Prevalence of minor cognitive deficits has increased as well and is currently reported to be detectable in 20 to 50% of patients [6, 7]. The most probable explanation for this increase is that many antiretroviral agents exhibit poor CSF and brain penetra- tion [8]; additionally, these agents, may fail to completely suppress HIV replication in the brain due to compartmental- ization of HIV-1 infection within the central nervous system (CNS). HIV establishes an inflammatory response within the CNS, resulting in macrophage activation. The inflammatory