Chronic inflammation and the role for cofactors (hepatitis C, drug abuse, antiretroviral drug toxicity, aging) in HAND persistence

Abstract

HIV-associated neurocognitive disorders (HAND) is a group of syndromes of varying degrees of cognitive impairment affecting up to 50 % of HIV-infected individuals. The neuropathogenesis of HAND is thought to be driven by HIV invasion and productive replication within brain perivascular macrophages and endogenous microglia, and to some degree by restricted infection of astrocytes. The persistence of HAND in individuals experiencing suppression of systemic HIV viral load with antiretroviral therapy (ART) is incompletely explained, and suggested factors include chronic inflammation, persistent HIV replication in brain macrophages, effects of aging on brain vulnerability, and co-morbid conditions including hepatitis C (HCV) co-infection, substance abuse, and CNS toxicity of ART, among other factors. This review discusses several of these conditions: chronic inflammation, co-infection with HCV, drugs of abuse, aging, and antiretroviral drug effects. Effectively managing these co-morbid conditions in individuals with and without HAND is critical for improving neurocognitive outcomes and decreasing HIV-associated morbidity.

Conflict of interest statement

Compliance with Ethics Guidelines

Conflict of Interest Alexander J. Gill and Dennis L. Kolson declare that they have no conflict of interest.

Figures

Fig. 1

CNS inflammatory effects of HIV and HCV infection of monocytes, macrophages, and microglia. CD14+/CD16+ monocytes can be infected by HCV and HIV and migrate across the endothelial barrier into the brain. Macrophages and microglia within the brain can support productive infection with HIV and HCV, resulting in the production of pro-inflammatory cytokines and neurotoxins (glutamate, Ntox, quinolinic acid). Those associated with HCV infection are depicted in the left-most macrophage image, and those associated with HIV infection are depicted in the right-most macrophage image. Such pro-inflammatory cytokines and neurotoxins have been shown to induce neuronal injury through direct and indirect (astrocyte-mediated) mechanisms