HIV-1 infection alters energy metabolism in the brain: Contributions to HIV-associated neurocognitive disorders

The brain is particularly sensitive to changes in energy supply. Defects in glucose utilization and mitochondrial dysfunction are hallmarks of nearly all neurodegenerative diseases and are also associated with the cognitive decline that occurs as the brain ages. Chronic neuroinflammation driven by glial activation is commonly implicated as a contributing factor to neurodegeneration and cognitive impairment. Human immunodeficiency virus-1 (HIV-1) disrupts normal brain homeostasis and leads to a spectrum of HIV-associated neurocognitive disorders (HAND). HIV-1 activates stress responses in the brain and triggers a state of chronic neuroinflammation. Growing evidence suggests that inflammatory processes and bioenergetics are interconnected in the propagation of neuronal dysfunction. Clinical studies of people living with HIV and basic research support the notion that HIV-1 creates an environment in the CNS that interrupts normal metabolic processes at the cellular level to collectively alter whole brain metabolism. In this review, we highlight reports of abnormal brain metabolism from clinical studies and animal models of HIV-1. We also describe diverse CNS cell-specific changes in bioenergetics associated with HIV-1. Moreover, we propose that attention should be given to adjunctive therapies that combat sources of metabolic dysfunction as a mean to improve and/or prevent neurocognitive impairments.