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Abstract
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.
GLOSSARY
- ARV=
- antiretroviral drug;
- cART=
- combined antiretroviral therapy;
- CI=
- confidence interval;
- HAND=
- HIV-associated neurocognitive disorders;
- MSK=
- Memorial Sloan-Kettering;
- NNRTI=
- nonnucleoside reverse transcriptase inhibitor;
- OR=
- odds ratio;
- SM=
- sphingolipid metabolite
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work.
Editorial, page 1480
Supplemental data at www.neurology.org
- Received August 29, 2012.
- Accepted in final form June 21, 2013.
- © 2013 American Academy of Neurology
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