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Persisting Inflammation and Chronic Immune Activation but Intact Cognitive Function in HIV-Infected Patients After Long-Term Treatment With Combination Antiretroviral Therapy

Pedersen, Karin K. MD*,†,‡; Pedersen, Maria MD, PhD; Gaardbo, Julie C. MD*,‡; Ronit, Andreas BSc*,‡; Hartling, Hans J. MD*,‡; Bruunsgaard, Helle MD, PhD; Gerstoft, Jan MD, DMSc*; Ullum, Henrik MD, PhD; Nielsen, Susanne D. MD, DMSc*

JAIDS Journal of Acquired Immune Deficiency Syndromes: July 1st, 2013 - Volume 63 - Issue 3 - p 272–279
doi: 10.1097/QAI.0b013e318289bced
Basic and Translational Science

Objectives: Impaired cognitive function in HIV-infected patients has been suggested. Treatment with combination antiretroviral therapy (cART) restores CD4+ cell counts and suppresses viral replication, but immune activation and inflammation may persist. The aim of the study was to examine if cognitive function in HIV-infected patients was related to immune activation and inflammation.

Methods: Sixty-one HIV-infected patients and 31 healthy controls were included. All patients were on treatment with cART, had suppressed viral replication, and had a mean CD4+ cell count of 522 cells/μL. Cognitive function was assessed using a test battery of neurocognitive tests. Plasma concentrations of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and β-2-microglobulin were measured. Immune activation (CD8+HLR-DR+CD38+ cells) was determined using flow cytometry. Multiple linear regression analysis was performed to identify relationship between cognitive scores and markers of inflammation and immune activation.

Results: HIV-infected patients had intact cognitive function compared with healthy controls. Higher levels of TNF-α, β-2-microglobulin, and chronic activated CD8+ cells were found in HIV-infected patients (P = 0.0002, P < 0.0001, and P = 0.021, respectively). Weak negative correlations were found between chronic activated CD8+ cells (β-coefficient = −0.277, P = 0.044), IL-6 (β-coefficient = −0.280, P = 0.014), and memory and learning.

Conclusions: HIV-infected patients on cART with undetectable viral load had an increased level of inflammation and immune activation. However, intact cognitive function was found, and only weak correlations were found between cognitive function and markers of inflammation and immune activation, indicating that peripheral inflammation and immune activation are not major drivers of cognitive decay in HIV-infected patients.

*Department of Infectious Diseases, Rigshospitalet, University Hospital of Copenhagen, Denmark;

Centre of Inflammation and Metabolism, Rigshospitalet, University Hospital of Copenhagen, Denmark; and

Department of Clinical Immunology, Rigshospitalet, University Hospital of Copenhagen, Denmark.

Correspondence to: Susanne D. Nielsen, Department of Infectious Diseases, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, DK 2100 Copenhagen Ø, Denmark (e-mail:

Supported by the Novo Nordisk Foundation; the Danish Council for Independent Research; Lundbeck Foundation; Lykfeldt grant; Torben and Alice Frimodts Foundation; Snedkermester Sophus Jacobsen and wife Astrid Jacobsens Foundation; Aase and Ejnar Danielsens Foundation; and Janssen.

The authors have no conflicts of interest to disclose.

Presented in part with a poster “Higher Level of Chronic Immune Activation in HIV-infected Patients Does Not Predict Cognitive Dysfunction” at the 13th European AIDS Conference, 2011, Belgrade, Serbia.

Received November 30, 2012

Accepted January 24, 2013

© 2013 Lippincott Williams & Wilkins, Inc.