Treating HIV Infection in the Central Nervous System

Area of Science:

• Neuroscience
• Infectious Diseases
• Pharmacology

Background:

• Combination antiretroviral treatment (cART) has significantly reduced HIV-associated dementia.
• However, a substantial number of HIV-positive individuals still experience neurocognitive impairment, impacting quality of life.
• Current prevention and management strategies for HIV-associated neurocognitive disorders (HAND) lack clear recommendations.

Purpose of the Study:

• To review drug penetration into the cerebrospinal fluid (CSF) and its impact on HIV in the CNS.
• To discuss viral and clinical consequences of varying drug exposure levels within the CNS.
• To explore potential interventions targeting underlying mechanisms of HAND.

Main Methods:

• Literature review focusing on drug penetration, viral dynamics, and clinical outcomes in the CNS of HIV patients.
• Analysis of identified risk factors and underlying mechanisms of HAND.
• Discussion of current and potential therapeutic interventions.

Main Results:

• Drug penetration into the CNS varies, influencing viral control and clinical outcomes.
• Persistent CNS immune activation, legacy effects, low-level viral replication, comorbidities, and antiretroviral neurotoxicity contribute to HAND.
• No definitive guidelines exist for HAND prevention and management.

Conclusions:

• HIV treatment in the CNS is complex, requiring a multidisciplinary approach.
• Understanding drug penetration and CNS-specific mechanisms is crucial for managing HAND.
• Further research and adjunctive therapies, including neuro-rehabilitation, are necessary.