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Alterations in cerebrospinal fluid chemokines are associated with maraviroc exposure and in vivo metabolites measurable by magnetic resonance spectroscopy.
Vera, Jaime H; Garvey, Lucy J; Allsop, Joanna M; Kaye, Steve; McClure, Myra O; Back, David; Taylor-Robinson, Simon D; Winston, Alan.
Afiliación
  • Vera JH; Department of Medicine, Imperial College, and Clinical Trials Centre, St Mary's Hospital, Norfolk Place, London, UK. j.vera@imperial.ac.uk
HIV Clin Trials ; 13(4): 222-7, 2012.
Article en En | MEDLINE | ID: mdl-22849963
BACKGROUND: Cerebrospinal (CSF) fluid biomarkers may be a useful tool for assessing the cerebral effects of antiretroviral therapy. OBJECTIVE: The aim of the study was to investigate the relationship between 4 CSF chemokines with maraviroc exposure and cerebral metabolite ratios (CMR) measured by magnetic resonance spectroscopy (1H-MRS) in HIV-infected individuals following maraviroc intensification. METHODS: CSF concentration of maraviroc and 4 chemokines (MCP-1, IP-10, MCP-4, and MIP-1ß), plasma concentration of maraviroc pre-CSF assessment, and right basal ganglia CMR were assessed in 12 male HIV-infected, neuro-asymptomatic adults after 14 days of antiretroviral therapy intensification with maraviroc 150 mg twice daily. The relationship between CSF analytes with both CMRs and plasma and CSF maraviroc concentrations were examined using Spearman correlation coefficient. RESULTS: Twelve subjects completed study procedures with baseline values as follows: mean (SD) age 42 (8) years, CD4+ cell count 503 (199) cells/µL, and plasma HIV RNA<50 copies/mL in most subjects. Mean (range, pg/mL) chemokine concentrations were IP-10, 1242 (190-8073); MCP-4, 6.52 (1-18); MCP-1, 702 (201-1618); and MIP-1ß, 42 (5-153). IP-10, MCP-4, and MIP-1ß were significantly associated with CMRs in the right basal ganglia with (1) lower concentrations of IP-10 correlating with higher N-acetyl aspartate to creatine ratios (NAA/Cr) and (2) higher concentrations of MCP-4 and MIP-1ß correlating with higher myoinositol to creatine (mI/Cr) ratios. There were no significant associations with MCP-1. Finally lower concentrations of IP-10 were significantly associated with higher maraviroc plasma trough concentration (r=-0.629, P=.028) but not CSF concentration (r=-0.308, P=.331). CONCLUSION: We hypothesize that the relationship between IP-10, MCP-4, and MIP-1ß with maraviroc exposure and CMRs may be associated with a direct cerebral effect of maraviroc.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Triazoles / Espectroscopía de Resonancia Magnética / Quimiocinas / Ciclohexanos / Inhibidores de Fusión de VIH / Antagonistas de los Receptores CCR5 Tipo de estudio: Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: HIV Clin Trials Asunto de la revista: SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS) / TERAPEUTICA Año: 2012 Tipo del documento: Article Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Triazoles / Espectroscopía de Resonancia Magnética / Quimiocinas / Ciclohexanos / Inhibidores de Fusión de VIH / Antagonistas de los Receptores CCR5 Tipo de estudio: Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: HIV Clin Trials Asunto de la revista: SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS) / TERAPEUTICA Año: 2012 Tipo del documento: Article Pais de publicación: Reino Unido