Date Published:
2013 Oct 22

Publication Type:
Journal Article

Authors:

V.Venkata Ra Bandaru
M.M. Mielke
N. Sacktor
J.C. McArthur
I. Grant
S. Letendre
L. Chang
V. Wojna
C. Pardo
P. Calabresi
S. Munsaka
N.J. Haughey

Secondary:
Neurology

Volume:
81

Pagination:
1492-9

Issue:
17

PMID:
24027056

URL:
https://pubmed.ncbi.nlm.nih.gov/24027056

DOI:
10.1212/WNL.0b013e3182a9565e

Keywords:
Adult;AIDS Dementia Complex;Antiretroviral Therapy, Highly Active;Biomarkers;Ceramides;Cholesterol;Female;HIV Infections;Humans;Lipid Metabolism Disorders;Longitudinal Studies;Male;Predictive Value of Tests;Sphingolipids

Abstract:
<p>OBJECTIVE: In this multicenter cohort study, we sought to identify prognostic and associative metabolic indicators for HIV-associated neurocognitive disorders (HAND).METHODS: A quantitative lipidomic analysis was conducted on 524 longitudinal CSF samples collected from 7 different performance sites across the mainland United States, Hawaii, and Puerto Rico. Subjects included HIV-infected individuals with longitudinal clinical and cognitive testing data and cognitively normal HIV-negative healthy controls.RESULTS: At baseline, HIV+ subjects could be differentiated from HIV- controls by reductions in a single ceramide species and increases in multiple forms of cholesterol. Perturbations in cholesterol metabolism and ceramide were influenced by combined antiretroviral therapy (cART) use. There were no cross-sectional baseline differences in any lipid metabolite when HIV+ subjects were grouped according to cognitive status. However, a single sphingolipid metabolite and reduced levels of esterified cholesterols were prognostic indicators of incident cognitive decline. Longitudinal patterns of these disturbances in sphingolipid and sterol metabolism suggest that a progressive disorder of lipid metabolism that is similar to disorders of lipid storage may contribute to the pathogenesis of HAND.CONCLUSIONS: These findings suggest that HIV infection and cART are independently associated with a CNS metabolic disturbance, identify surrogate markers that are prognostic for cognitive decline, and implicate a lipid storage-like disorder in the progression of HAND.</p>