Diagnostic and prognostic biomarkers for HAND

Area of Science:

• Neuroscience
• Infectious Diseases
• Biomarker Discovery

Background:

• The 2007 nosology update classified HIV-1-associated neurocognitive disorders (HAND) primarily as neurocognitive disorders.
• Current diagnostic tools for HAND lack the necessary sensitivity and specificity, particularly in the post-combination antiretroviral therapy (cART) era.
• There is a critical need for innovative biomarkers to diagnose and predict HAND progression.

Purpose of the Study:

• To review the utility and challenges of proposed biomarkers for diagnosing and predicting HAND.
• To evaluate neurofilament light chain concentration, amyloid and tau proteins, resting-state fMRI, and prepulse inhibition (PPI).
• To identify a sensitive and specific biomarker for milder forms of neurocognitive impairment (NCI) in the context of cART.

Main Methods:

• Literature review of studies investigating NFL, amyloid/tau proteins, fMRI, and PPI as biomarkers for HAND.
• Analysis of diagnostic accuracy, sensitivity, and specificity data for each proposed biomarker.
• Evaluation of prognostic capabilities, particularly for milder NCI.

Main Results:

• Neurofilament light chain, amyloid/tau proteins, and fMRI show genotypic differences but face limitations like invasiveness, lack of specificity, and cost.
• Prepulse inhibition (PPI) demonstrates high diagnostic accuracy (86.7-97.1%), sensitivity (89.3-100%), and specificity (79.5-94.1%) for HAND.
• PPI shows potential as a prognostic biomarker, predicting later NCI with high regression coefficients (r > 0.8).

Conclusions:

• While NFL, amyloid/tau, and fMRI have limitations, PPI emerges as a powerful diagnostic biomarker for HAND.
• PPI offers a brief, noninvasive, and promising prognostic biomarker for milder forms of NCI in the post-cART era.
• Further research is needed, potentially exploring combinations of CSF/plasma markers for enhanced diagnostic sensitivity.