New horizons in HIV neuropathogenesis: thinking beyond the brain

Area of Science:

• Neuroscience
• Immunology
• Infectious Diseases

Background:

• Neurocognitive disorders and neuropathology affect people with HIV (PWH) even with viral suppression via antiretroviral therapy (ART).
• Mechanisms driving persistent neuropathology in PWH are not fully understood, with limited therapeutic options available.
• This review focuses on emerging evidence regarding HIV-associated neuropathology in ART-suppressed PWH, emphasizing the gut-brain axis.

Purpose of the Study:

• To review current evidence on HIV-associated neuropathology in ART-suppressed PWH.
• To explore the role of the gut-brain axis in persistent neuroinflammation and cognitive decline.
• To identify potential therapeutic strategies targeting viral transcription and inflammation.

Main Methods:

• Literature review of recent studies on HIV neuropathology.
• Analysis of evidence implicating the central nervous system (CNS) as an HIV reservoir.
• Examination of the role of systemic inflammation and gut barrier dysfunction.

Main Results:

• The CNS acts as a stable HIV reservoir, promoting microglial activation and synaptic injury.
• Systemic inflammation and gut barrier dysfunction contribute to neuroinflammation and cognitive decline in PWH.
• Gut inflammation can lead to enteric nervous system (ENS) dysfunction, exacerbating neuroinflammation.

Conclusions:

• HIV neuropathology in ART-suppressed PWH results from combined CNS HIV reservoirs, neuroinflammation, systemic activation, and gut injury.
• Residual brain infection is not the sole cause of neuropathology.
• Future interventions should target viral transcription, gut integrity, and systemic inflammation to prevent and treat HIV-associated neuropathology.