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

TitlePlasma and Cerebrospinal Fluid Biomarkers Predict Cerebral Injury in HIV-Infected Individuals on Stable Combination Antiretroviral Therapy.
Publication TypeJournal Article
Year of Publication2015
AuthorsAnderson, AM, Harezlak, J, Bharti, AR, Mi, D, Taylor, MJ, Daar, ES, Schifitto, G, Zhong, J, Alger, JR, Brown, MS, Singer, EJ, Campbell, TB, McMahon, DD, Buchthal, S, Cohen, R, Yiannoutsos, CT, Letendre, S, Navia, BA
Corporate AuthorsHIV Neuroimaging Consortium,
JournalJ Acquir Immune Defic Syndr
Volume69
Issue1
Pagination29-35
Date Published2015 May 1
ISSN1944-7884
KeywordsAdult, AIDS Dementia Complex, Anti-Retroviral Agents, Antiretroviral Therapy, Highly Active, Biomarkers, Brain, Cerebrospinal Fluid, Cohort Studies, Cross-Sectional Studies, Female, HIV Infections, Humans, Male, Middle Aged, Plasma
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.

DOI10.1097/QAI.0000000000000532
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID25622053
PubMed Central IDPMC4424074
Grant ListAI068614 / AI / NIAID NIH HHS / United States
AI069432 / AI / NIAID NIH HHS / United States
CA172050 / CA / NCI NIH HHS / United States
HL098996 / HL / NHLBI NIH HHS / United States
HL121816 / HL / NHLBI NIH HHS / United States
K23 MH085512 / MH / NIMH NIH HHS / United States
K23 MH085512 / MH / NIMH NIH HHS / United States
K23 MH095679 / MH / NIMH NIH HHS / United States
K23 MH095679 / MH / NIMH NIH HHS / United States
K24 MH097673 / MH / NIMH NIH HHS / United States
K24 MH097673 / MH / NIMH NIH HHS / United States
K99 AA020235 / AA / NIAAA NIH HHS / United States
K99 AA020235 / AA / NIAAA NIH HHS / United States
MH092225 / MH / NIMH NIH HHS / United States
P01 AA019072 / AA / NIAAA NIH HHS / United States
P01 AA019072 / AA / NIAAA NIH HHS / United States
P30 AI042853 / AI / NIAID NIH HHS / United States
P30 AI042853 / AI / NIAID NIH HHS / United States
P30 MH062512 / MH / NIMH NIH HHS / United States
R01 CA172050 / CA / NCI NIH HHS / United States
R01 DK089070 / DK / NIDDK NIH HHS / United States
R01 DK089070 / DK / NIDDK NIH HHS / United States
R01 MH074368 / MH / NIMH NIH HHS / United States
R01 MH074368 / MH / NIMH NIH HHS / United States
R01 MH092225 / MH / NIMH NIH HHS / United States
R01 MH099921 / MH / NIMH NIH HHS / United States
R01 NS080655 / NS / NINDS NIH HHS / United States
R01 NS080655 / NS / NINDS NIH HHS / United States
R01 NS36524 / NS / NINDS NIH HHS / United States
R24 TW008881 / TW / FIC NIH HHS / United States
RR025780 / RR / NCRR NIH HHS / United States
TW008881 / TW / FIC NIH HHS / United States
U01 HL098996 / HL / NHLBI NIH HHS / United States
U01 HL121816 / HL / NHLBI NIH HHS / United States
U01 MH083500 / MH / NIMH NIH HHS / United States
U24 MH100928 / MH / NIMH NIH HHS / United States
U24 MH100929 / MH / NIMH NIH HHS / United States
UL1 RR025780 / RR / NCRR NIH HHS / United States
UM1 AI068614 / AI / NIAID NIH HHS / United States
UM1 AI069432 / AI / NIAID NIH HHS / United States