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. 2015 May 1;69(1):29-35.
doi: 10.1097/QAI.0000000000000532.

Plasma and Cerebrospinal Fluid Biomarkers Predict Cerebral Injury in HIV-Infected Individuals on Stable Combination Antiretroviral Therapy

Albert M Anderson  1 , Jaroslaw Harezlak, Ajay Bharti, Deming Mi, Michael J Taylor, Eric S Daar, Giovanni Schifitto, Jianhui Zhong, Jeffry R Alger, Mark S Brown, Elyse J Singer, Thomas B Campbell, Deborah D McMahon, Steven Buchthal, Ronald Cohen, Constantin Yiannoutsos, Scott L Letendre, Bradford A Navia; HIV Neuroimaging Consortium
Affiliations

Plasma and Cerebrospinal Fluid Biomarkers Predict Cerebral Injury in HIV-Infected Individuals on Stable Combination Antiretroviral Therapy

Albert M Anderson et al. J Acquir Immune Defic Syndr. .

Abstract

Objectives: HIV-associated brain injury persists despite combination antiretroviral therapy, but contributing factors remain poorly understood. We postulated that inflammation-associated biomarkers will be associated with cerebral injury on proton magnetic resonance spectroscopy in chronically HIV-infected subjects.

Methods: Five biomarkers were measured in 197 HIV-infected subjects: soluble CD14, MCP-1, IP-10, MIP-1β, and fractalkine. Levels of N-acetyl aspartate (NAA), Choline (Cho), Myoinositol (MI), Glutamate + Glutamine (Glx), and Creatine (Cr) were acquired in the midfrontal cortex (MFC), frontal white matter, and basal ganglia (BG). Predictive models were built through linear regression, and the best models were chosen using the Akaike Information Criterion.

Results: Increases in plasma or CSF MCP-1 were associated with lower NAA/Cr in the MFC and BG, whereas metabolite changes in the frontal white matter for NAA/Cr, GlxCr, and Cho/Cr were explained almost exclusively by a single factor, sCD14. Plasma and CSF levels of this factor were also significantly associated with Glx/Cr in MFC and BG. Higher CSF FKN was associated with higher NAA/Cr in BG. Best predictors for higher Cho/Cr in BG and MFC were CSF sCD14 and CSF MIP-1β. Plasma and CSF IP-10 were only associated with Cho/Cr in MFC. Of the 3 models that simultaneously accounted for both plasma and CSF, there were more associations between CSF biomarkers and magnetic resonance spectroscopy metabolites.

Conclusions: Markers of inflammation and immune activation, in particular MCP-1 and sCD14, predominantly reflecting CNS sources, contribute to the persistence of brain injury in a metabolite and region-dependent manner in chronically HIV-infected patients on stable combination antiretroviral therapy.

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Conflict of interest statement

Disclosures/Conflict of interest:

Dr. Anderson previously received research support from Gilead Sciences. He is currently funded by NIHK23MH095679. No conflicts of interest

Dr. Harezlak is supported by NIH1R01NS080655-01A1 and NIH1R01DK089070. No conflicts of interest

Dr. Bharti is funded by NIH K23MH085512. No conflicts of interest

Dr. Mi reports no disclosures and no conflicts of interest

Dr. Taylor reports no disclosures and no conflicts of interest.

Dr. Daar has served as a consultant/advisor for Abbvie, Bristol Myers Squibb, Gilead, Janssen, Merck, Teva and Viiv as well as received research grant support from Bristol Myers Squibb, Gilead and ViiV. No conflicts of interest

Dr. Schifitto reports no disclosures and no conflicts of interest

Dr. Zhong reports no disclosures and no conflicts of interest

Dr. Alger reports no disclosures and no conflicts of interest

Dr. Brown reports no disclosures and no conflicts of interest

Dr. Singer has received support from NIH: 1U24MH100929 and 1U01MH083500 and also serves as a site investigator for Pfizer. No conflicts of interest

Dr. Campbell previously served as a consultant for Gilead Sciences. He receives funding from the following NIH grants AI069432, RR025780, HL098996, AI068614 TW008881, CA172050 and HL121816. No conflicts of interest.

Dr. McMahon reports no disclosures and no conflicts of interest

Dr. Buchthal reports no disclosures and no conflicts of interest

Dr. Cohen was funded by the following NIH grants: IH R01MH074368, 403 P01AA019072, K99AA020235, P30AI042853. He also served as a reviewer on NIH study sections of IRGs that reviewed research proposals for NIA and NIDA on topics related to HIV effects on the brain. No conflicts of interest.

Dr. Yiannoutsos reports no disclosures and no conflicts of interest

Dr. Letendre is currently funded by NIH grants R01MH092225 and K24MH097673. No conflicts of interest.

Dr. Navia reports NIH funding R01NS36524. No conflicts of interest.

Figures

Figure 1
Figure 1
In all figures, the red line shows the linear regression fit of the association between the soluble biomarker levels in CSF and cerebral metabolite values, the green shaded area indicates the 95% pointwise confidence interval, and the blue dots are the raw data. Figures 1A (left): Higher sCD14 levels in CSF correlate with lower NAA/Cr ratios is FWM. Figure 1B (center): Higher MCP-1 levels in CSF correlate with lower NAA/Cr ratios is BG. Figure 1C (right): Lower FKN levels in CSF correlate with lower NAA/Cr ratios in BG.
See this image and copyright information in PMC

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