Plasma and Cerebrospinal Fluid Biomarkers Predict Cerebral Injury in HIV-Infected Individuals on Stable Combination Antiretroviral Therapy.
Title | Plasma and Cerebrospinal Fluid Biomarkers Predict Cerebral Injury in HIV-Infected Individuals on Stable Combination Antiretroviral Therapy. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Anderson, AM, Harezlak, J, Bharti, A, 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, C, Letendre, SL, Navia, BA |
Corporate Authors | HIV Neuroimaging Consortium, |
Journal | J Acquir Immune Defic Syndr |
Volume | 69 |
Issue | 1 |
Pagination | 29-35 |
Date Published | 2015 May 01 |
ISSN | 1944-7884 |
Keywords | Adult, AIDS Dementia Complex, Anti-Retroviral Agents, Antiretroviral Therapy, Highly Active, Biomarkers, Brain, Cerebrospinal Fluid, Cohort Studies, Cross-Sectional Studies, External, 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. |
DOI | 10.1097/QAI.0000000000000532 |
Alternate Journal | J Acquir Immune Defic Syndr |
PubMed ID | 25622053 |
PubMed Central ID | PMC4424074 |
Grant List | R01 CA172050 / CA / NCI NIH HHS / United States U24 MH100929 / MH / NIMH NIH HHS / United States R01 NS036524 / NS / NINDS NIH HHS / United States K24 MH097673 / MH / NIMH NIH HHS / United States U01 MH083500 / MH / NIMH NIH HHS / United States K23 MH085512 / MH / NIMH NIH HHS / United States CA172050 / CA / NCI NIH HHS / United States R01 MH092225 / MH / NIMH NIH HHS / United States HL098996 / HL / NHLBI NIH HHS / United States K99 AA020235 / AA / NIAAA NIH HHS / United States UM1 AI069432 / AI / NIAID NIH HHS / United States UL1 RR025780 / RR / NCRR NIH HHS / United States U24 MH100928 / MH / NIMH NIH HHS / United States TW008881 / TW / FIC NIH HHS / United States R01 NS36524 / NS / NINDS NIH HHS / United States P30 AG028740 / AG / NIA NIH HHS / United States UM1 AI068614 / AI / NIAID NIH HHS / United States U01 AI069432 / AI / NIAID NIH HHS / United States HL121816 / HL / NHLBI NIH HHS / United States R01 MH099921 / MH / NIMH NIH HHS / United States P30 MH062512 / MH / NIMH NIH HHS / United States U01 HL121816 / HL / NHLBI NIH HHS / United States UL1 TR001082 / TR / NCATS NIH HHS / United States R01 NS080655 / NS / NINDS NIH HHS / United States MH092225 / MH / NIMH NIH HHS / United States P30 AI042853 / AI / NIAID NIH HHS / United States RR025780 / RR / NCRR NIH HHS / United States AI069432 / AI / NIAID NIH HHS / United States P01 AA019072 / AA / NIAAA NIH HHS / United States AI068614 / AI / NIAID NIH HHS / United States R01 DK089070 / DK / NIDDK NIH HHS / United States K23 MH095679 / MH / NIMH NIH HHS / United States R01 MH074368 / MH / NIMH NIH HHS / United States U01 HL098996 / HL / NHLBI NIH HHS / United States R24 TW008881 / TW / FIC NIH HHS / United States |