Changes in cardiovascular biomarkers in HIV-infected patients switching from ritonavir-boosted protease inhibitors to raltegravir

Esteban Martínez, Polyana M. D'Albuquerque, Josep M. Llibre, Felix Gutierrez, Daniel Podzamczer, Antonio Antela, Juan Berenguer, Pere Domingo, Xabier Moreno, Ignacio Perez, Judit Pich, José M. Gatell

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    Abstract

    Background: Switching from boosted protease inhibitors (PI/r) to raltegravir (RAL) results in a better plasma lipid profile than continuing PI/r. Whether this strategy affects plasma biomarkers associated with atherosclerosis is unknown. Methods: We assessed 48-week changes in fasting lipids and several biomarkers including serum high-sensitivity C-reactive protein (hsCRP), monocyte chemoattractant protein 1 (MCP-1), osteoprotegerin, interleukin (IL) 6, IL-10, tumor necrosis factor alpha (TNF-α), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin and P-selectin, adiponectin, insulin, and D-dimer in otherwise healthy, virologically suppressed HIV-infected patients treated with PI/r who randomly switched from PI/r to RAL or continued with PI/r in the SPIRAL trial. Biomarkers and lipids at baseline and 48-week changes between both study arms were compared. Correlations between changes in biomarkers and changes in lipids were also evaluated. Results: Of 273 patients initiating study drugs in the SPIRAL trial, 233 (119 RAL, 114 PI/r) remained on allocated therapy for 48 weeks and had sera available for the purpose of this substudy. Triglycerides (-28%, P < 0.0001), total (-14%, P < 0.0001), low-density lipoprotein (-9%, P = 0.0069), and high-density lipoprotein (-10%, P = 0.0017) cholesterol decreased in RAL relative to the PI/r group. Among biomarkers, hsCRP (-40%, P < 0.0001), MCP-1 (-20%, P = 0.0003), osteoprotegerin (-13%, P = 0.0024), IL-6 (-46%,P < 0.0001), TNF-α (-27%, P = 0.0011), insulin (-26%, P < 0.0001), and D-dimer (-8%, P = 0.0187) decreased in RAL relative to PI/r group, whereas IL-10 (+1%, P = 0.7773), ICAM-1 (-6%, P = 0.1255), VCAM-1(0%, P = 0.8671), E-selectin (-9%, P = 0.2174), P-selectin (-6%, P = 0.3865), and adiponectin (+8%, P = 0.2028) remained unchanged. Biomarkers and lipids changes at 48 weeks were weakly correlated. Conclusion: Switching from PI/r to RAL induced significant changes in several cardiovascular biomarkers that were not completely explained by lipid changes. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.
    Original languageEnglish
    Pages (from-to)2315-2326
    JournalAIDS
    Volume26
    Issue number18
    DOIs
    Publication statusPublished - 28 Nov 2012

    Keywords

    • cardiovascular biomarkers
    • protease inhibitors
    • raltegravir
    • switching

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    Martínez, E., D'Albuquerque, P. M., Llibre, J. M., Gutierrez, F., Podzamczer, D., Antela, A., Berenguer, J., Domingo, P., Moreno, X., Perez, I., Pich, J., & Gatell, J. M. (2012). Changes in cardiovascular biomarkers in HIV-infected patients switching from ritonavir-boosted protease inhibitors to raltegravir. AIDS, 26(18), 2315-2326. https://doi.org/10.1097/QAD.0b013e328359f29c