TABLE 1.

Comparison of Proposed Biomarkers

Biomarker	Advantage & Utility	Disadvantage & Constraints	GOAL: Diagnostic Biomarker	GOAL: Prognostic Biomarker
NFL Chain Concentration	Plasma and CSF concentrations highly correlated; Sensitive to the initiation of cART	Alterations have been observed in other neurodegenerative diseases (e.g., AD, multiple sclerosis), and thus, it is not disease specific	Inconsistent relationship with NCI that may be driven primarily by cART	In the pre-cART era, increases in NFL concentration were associated with presentation of ADC
Amyloid and Tau Proteins	Distinct pathology from AD	Invasive procedure needed for CSF measurements	Selective relationships between NCI and protein markers; Unable to distinguish between milder forms of NCI and controls, despite the use of multiple markers	CSF Aβ−42 and p-tau have been utilized as a prognostic biomarker for the conversion from MCI to AD
Resting-State fMRI	Brief, non-invasive procedure	Currently unclear what changes in BOLD signaling indicate mechanistically; Inconsistencies between studies	Inconsistent relationship between fMRI measures and NCI	No changes in resting-state fMRI relative to controls were observed in a two-year follow-up
Prepulse Inhibition	Brief, non-invasive procedure; Clinically translational experimental paradigm	Alterations have been observed in other diseases, albeit evidence in other neurodegenerative disease (e.g., AD) is limited	Diagnostic utility generalizes across two experimental paradigms (i.e., cross-modal PPI, gap-PPI), the functional lifespan, sensory modalities, and biological sex; Overall high accuracy, sensitivity, and specificity	Early neurocognitive impairments in PPI predict later alterations in higher order cognitive functions (r≥0.81)

NFL=Neurofilament Light; CSF=Cerebrospinal Fluid; cART=Combination Antiretroviral Therapy; AD=Alzheimer’s disease; NCI=Neurocognitive Impairments; ADC=AIDS Dementia Complex; Aβ−42=Amyloid β 1–42; MCI=Milder Cognitive Impairment; fMRI=Functional Magnetic Resonance Imaging; BOLD=Blood Oxygenation Level Dependent; PPI=Prepulse Inhibition; gap-PPI=Gap Prepulse Inhibition