Persistent Intrathecal Immune Activation in HIV-1-Infected Individuals on Antiretroviral Therapy

Yilmaz, Aylin MD, PhD*; Price, Richard W MD†; Spudich, Serena MD†; Fuchs, Dietmar PhD‡; Hagberg, Lars MD, PhD*; Gisslén, Magnus MD, PhD*

JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e31815ace97
Clinical Science

Background: Neopterin is a well-established marker of macrophage activation. The cerebrospinal fluid (CSF) neopterin levels are elevated in most HIV-1-infected individuals and decrease significantly after initiation of antiretroviral therapy (ART). Unexpectedly, CSF concentrations often remain mildly abnormal even in patients treated for a long time with suppressive ART. The aims of this study were to analyze if persistently elevated CSF neopterin levels were associated with the type of antiretroviral regimen or with low-level CSF HIV-1 concentrations and to evaluate if plasma HIV-1 RNA levels correlated to lingering CSF neopterin concentrations in patients with effective ART.

Methods: One hundred fifty-seven chronically HIV-1-infected patients with stable ART for ≥6 months and no neurologic symptoms were included, and 193 HIV-1-infected patients without ART served as controls. Neopterin was analyzed with a radioimmunoassay or an enzyme-linked immunosorbent assay. HIV-1 RNA quantification was performed with the Roche Amplicor assay (version 1.5; Hoffman-La Roche, Basel, Switzerland). Two quantitative HIV-1 RNA assays with sensitivities ≤2.5 copies/mL were used in 40 samples.

Results: As anticipated, HIV-1 RNA and CSF neopterin levels were markedly lower in patients on ART compared with untreated controls. No significant difference in CSF neopterin concentrations was found between those treated with protease inhibitor- and nonnucleoside reverse transcriptase inhibitor-based regimens in combination with 2 nucleoside analogues. Subjects with CSF HIV-1 RNA loads <2.5 copies/mL had the lowest CSF neopterin levels. Plasma viral load had no impact on intrathecal immune activation in cases with CSF viral loads <50 copies/mL.

Conclusion: The persistent intrathecal cell-mediated immune response was associated with CSF viral load but not with treatment regimen in individuals on ART.

Author Information

From the *Department of Infectious Diseases, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden; †Department of Neurology, University of California San Francisco, San Francisco General Hospital, San Francisco, CA; and the ‡Division of Biological Chemistry, Biocentre, Innsbruck Medical University, Innsbruck, Austria.

Received for publication June 27, 2007; accepted September 10, 2007.

Supported by grants from the National Institutes of Health (NINDS R01 NS43103-01), Medical Faculty of Göteborg University (ALFGBG-2874), Göteborg Medical Society, Swedish Physicians Against AIDS Research Foundation, and Government of the State of the Austrian Tyrol.

Correspondence to: Aylin Yilmaz, MD, PhD, Department of Infectious Diseases, Sahlgrenska University Hospital/Östra, Smörslottsgatan 1, 416 85 Göteborg, Sweden (e-mail:

© 2008 Lippincott Williams & Wilkins, Inc.