Abstract Details

Title Distinct Neurodegenerative and Neuroinflammatory Subtypes of HIV-associated Neurocognitive Disorders (HAND)

Topic Infectious Disease

Presentation(s) S29 - NeuroHIV: Pathophysiology and Clinical Phenotypes (4:36 PM-4:47 PM)

Poster/Presentation
Number 007

Background HAND has been defined by poor neuropsychological (NP) testing performance, yet the criteria are nonspecific and there is a high false-positive rate. This has made identifying biomarkers difficult because the causes of HAND do not reflect a single disease entity.

Objective To identify distinct HIV(+) groups defined by CSF abnormalities and compare these groups to those with a normal CSF profile to determine associations with clinical outcomes.

Design/Methods

Participants completed a comprehensive NP battery and a research lumbar puncture. HIV(+) (n=67) and HIV(-) control (n=21) groups had no differences in age, sex, or race. All HIV(+) participants had a plasma HIV viral load <40 c/ml (median time on antiretroviral therapy 12.7 years). The neurodegenerative and neuroinflammatory groups were defined by those HIV(+) individuals with a CSF level of neurofilament light chain (NFL) or TNF-alpha, respectively, measured by Quanterix SIMOA immunoassay, more than three standard deviations above the control group mean. Among the cytokines measured, TNF-alpha was used to define the neuroinflammatory group because it had the greatest difference between the HIV(+) and control groups (p<0.01).

Results

Compared to those with a normal CSF profile, the neurodegenerative group (n=9) was more likely to meet HAND criteria (75% vs. 18%, p<0.01) and have an abnormal GDS (83% vs. 21%, p<0.01). There were no differences in the proportion with CSF escape (13% vs. 12%). The neuroinflammatory group (n=15) had no difference in the proportion with HAND compared to those with a normal CSF profile, and there was a slight trend toward having more CSF escape (20% vs. 8%, p=0.2).

Conclusions By defining subsets within the HIV (+) group using CSF abnormalities, we have demonstrated that different pathogenic mechanisms exist within this population, with different clinical outcomes for each group. Essentially, what has been defined traditionally as HAND represents distinct diseases that require unique interventions for future research.

Authors/Disclosures
Bryan Smith, MD (NIH) PRESENTER	Dr. Smith has nothing to disclose.
	No disclosure on file
Elizabeth Horne	No disclosure on file
	No disclosure on file
	No disclosure on file
Joseph Snow, PhD (NIMH)	Dr. Snow has received research support from NIH/NIMH.
Avindra Nath, MD, MBBS, FAAN (National Institutes of Health)	Dr. Nath has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Nath has received research support from National Institutes of Health. The institution of Dr. Nath has received research support from ALS Association. Dr. Nath has received intellectual property interests from a discovery or technology relating to health care.

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