HIV-Associated Apathy/Depression and Neurocognitive Impairments Reflect Persistent Dopamine Deficits

Area of Science:

• Neuroscience
• Virology
• Pharmacology

Background:

• Human immunodeficiency virus type 1 (HIV-1) infection is associated with significant neurocognitive impairments and affective disorders.
• Dopaminergic system dysfunction is a suspected underlying cause of these neurological deficits.

Purpose of the Study:

• To critically review the evidence for alterations in the dopaminergic system due to HIV-1 viral protein exposure.
• To examine the impact of combination antiretroviral therapy (cART) on dopaminergic function in HIV-1 positive individuals.
• To explore potential mechanisms linking HIV-1 infection to dopamine deficits.

Main Methods:

• Literature review examining neurochemical measurements (e.g., high-performance liquid chromatography, microdialysis, fast-scan cyclic voltammetry).
• Analysis of neurocognitive and behavioral outcomes in HIV-1 infected individuals.
• Evaluation of studies on the pharmacological effects of cART on the dopaminergic system.
• Investigation into the role of microglia infection by HIV-1 proteins.

Main Results:

• Basal dopamine levels vary by brain region and measurement technique.
• Chronic HIV-1 viral protein exposure is consistently linked to decreased dopamine concentrations.
• Neurocognitive deficits and apathy in HIV-1 are consistent with dopaminergic dysfunction.
• No direct evidence shows cART pharmacologically impacts the dopaminergic system.
• HIV-1 infection of microglia is a potential mechanism for dopamine depletion.

Conclusions:

• Long-term exposure to HIV-1 viral proteins leads to a persistent decrease in dopaminergic function.
• This dopaminergic deficit contributes to neurocognitive impairments and apathy in HIV-1.
• Effective treatments for HIV-1-associated neurological and affective symptoms require strategies to restore dopamine function.