Treating viruses in the brain: Perspectives from NeuroAIDS

Area of Science:

• Neuroscience
• Infectious Diseases
• Pharmacology

Background:

• Antiretroviral therapy (ART) achieves systemic HIV suppression but fails to eliminate persistent viral reservoirs.
• Persistent HIV in the brain is linked to HIV-associated neurocognitive disorders (HAND).
• Inadequate ART concentrations in the central nervous system (CNS) are a key factor in HAND development.

Purpose of the Study:

• To review current knowledge on antiretroviral drug exposure within the brain.
• To discuss the impact of comorbidities on antiretroviral efficacy in the CNS.
• To highlight the need for improved understanding of antiretroviral brain penetration for neuroAIDS therapeutics.

Main Methods:

• Review of existing literature on antiretroviral drug concentrations in human and animal brain tissue.
• Analysis of cerebrospinal fluid (CSF) as a surrogate marker for CNS drug exposure.
• Examination of factors influencing antiretroviral efficacy within the brain.

Main Results:

• Information on antiretroviral drug exposure specifically within the brain is limited.
• Cerebrospinal fluid (CSF) drug concentrations are often poor predictors of actual brain drug exposure.
• Comorbidities can significantly impact antiretroviral efficacy in the CNS.

Conclusions:

• Despite systemic viral suppression, HIV persists in the brain, leading to HAND.
• Current methods for assessing CNS drug exposure, like CSF levels, are insufficient.
• Enhanced understanding of antiretroviral brain penetration is essential for developing effective neuroAIDS treatments.