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

Abstract

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. 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. 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. 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.