Human immunodeficiency virus-associated neurocognitive disorders: Mind the gap

Area of Science:

• Neuroscience
• Infectious Diseases
• Immunology

Background:

• Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HANDs) are common, even with potent antiretroviral therapy (ART).
• Improved survival due to ART highlights the impact of comorbidities like hepatitis C coinfection and aging on neurological function.
• A significant therapeutic gap exists between ART's effects and full neurological recovery.

Purpose of the Study:

• To review the clinical features and treatment implications of HANDs.
• To explore the underlying pathophysiology of HANDs and the reasons for the therapeutic gap.
• To discuss animal models that illuminate HANDs mechanisms.

Main Methods:

• Literature review focusing on clinical features, pathophysiology, and therapeutic strategies for HANDs.
• Analysis of the role of persistent immune activation in the central nervous system.
• Examination of animal models for understanding HANDs mechanisms.

Main Results:

• Aberrant and sustained immune activation, triggered by HIV infection of brain macrophages, is a key factor in HANDs development.
• This immune activation contributes to the incomplete neurological recovery observed despite ART.
• Animal models have been crucial in elucidating the mechanisms of HANDs.

Conclusions:

• Persistent central nervous system inflammation is a critical driver of HANDs.
• Novel therapeutic approaches targeting this inflammation are necessary to bridge the existing treatment gap.
• Addressing persistent neuroinflammation is key to improving neurological outcomes in individuals with HIV.