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

Clin Dev Immunol. 2012:2012:467154. doi: 10.1155/2012/467154. Epub 2012 Mar 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Dementia Complex / etiology
  • AIDS Dementia Complex / immunology
  • AIDS Dementia Complex / virology
  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • Cognition Disorders / etiology
  • Cognition Disorders / immunology*
  • Cognition Disorders / virology
  • Cross-Sectional Studies
  • Cytokines / biosynthesis
  • Cytokines / cerebrospinal fluid*
  • Cytokines / immunology
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • RNA, Viral / blood
  • RNA, Viral / cerebrospinal fluid*
  • RNA, Viral / immunology
  • Viral Load
  • Virus Replication

Substances

  • Anti-HIV Agents
  • Cytokines
  • RNA, Viral