Sevelamer does not decrease lipopolysaccharide or soluble CD14 levels but decreases soluble tissue factor, low-density lipoprotein (LDL) cholesterol, and oxidized LDL cholesterol levels in individuals with untreated HIV infection

Netanya G Sandler, Xinyan Zhang, Ronald J Bosch, Nicholas T Funderburg, Andrew I Choi, Janet K Robinson, Derek M Fine, Robert W Coombs, Jeffrey M Jacobson, Alan L Landay, Daniel C Douek, Randall Tressler, Sarah W Read, Cara C Wilson, Steven G Deeks, Michael M Lederman, Rajesh T Gandhi, AIDS Clinical Trials Group A5296 Team, Jennifer Tiu, Jennifer Janik, Ruth Ebiasah, Thucuma Sise, Gene Morse, George Bishopric, Michael Klebert, LuAnn Borowski, Paul Harding, Amy Gonzalez, Russell Tracy, Brian Claggett, Alicarmen Alvarez, Tamara James, Patricia Walton, Kristen Allen, Eric Daar, Ruben Lopez, Pablo Tebas, Aleshia Thomas, Amy Sbrolla, Teri Flynn, Kim Whitely, Traci Davis, Donna McGregor, Babafemi Taiwo, Christine Hurley, Jordan Lake, Annie Luetkemeyer, Anna Smith, Carl J Fichtenbaum, Jan M Stockton, Kristine Griesmer, Graham Ray, Hector H Bolivar, Margaret A Fischl, Mary Adams, Michael K Klebert, Michael Royal, Netanya G Sandler, Xinyan Zhang, Ronald J Bosch, Nicholas T Funderburg, Andrew I Choi, Janet K Robinson, Derek M Fine, Robert W Coombs, Jeffrey M Jacobson, Alan L Landay, Daniel C Douek, Randall Tressler, Sarah W Read, Cara C Wilson, Steven G Deeks, Michael M Lederman, Rajesh T Gandhi, AIDS Clinical Trials Group A5296 Team, Jennifer Tiu, Jennifer Janik, Ruth Ebiasah, Thucuma Sise, Gene Morse, George Bishopric, Michael Klebert, LuAnn Borowski, Paul Harding, Amy Gonzalez, Russell Tracy, Brian Claggett, Alicarmen Alvarez, Tamara James, Patricia Walton, Kristen Allen, Eric Daar, Ruben Lopez, Pablo Tebas, Aleshia Thomas, Amy Sbrolla, Teri Flynn, Kim Whitely, Traci Davis, Donna McGregor, Babafemi Taiwo, Christine Hurley, Jordan Lake, Annie Luetkemeyer, Anna Smith, Carl J Fichtenbaum, Jan M Stockton, Kristine Griesmer, Graham Ray, Hector H Bolivar, Margaret A Fischl, Mary Adams, Michael K Klebert, Michael Royal

Abstract

Abnormal levels of inflammation are associated with cardiovascular disease and mortality in human immunodeficiency virus (HIV)-infected patients. Microbial translocation, which may cause inflammation, is decreased by sevelamer in patients undergoing hemodialysis. In this single-arm study, we evaluated the effects of 8 weeks of sevelamer therapy on 36 HIV-infected subjects who were not receiving antiretroviral therapy. Sevelamer did not significantly change markers of microbial translocation, inflammation, or T-cell activation. During sevelamer treatment, however, levels of soluble tissue factor, low-density lipoprotein (LDL) cholesterol, and oxidized LDL cholesterol decreased significantly, whereas D-dimer levels increased. Thus, in this study population, sevelamer did not reduce microbial translocation but may have yielded cardiovascular benefits.

Clinical trials registration: NCT 01543958.

Trial registration: ClinicalTrials.gov NCT01543958.

Keywords: HIV; LDL; LPS; microbial translocation; oxLDL; sCD14; sevelamer; soluble tissue factor.

© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Figures

Figure 1.
Figure 1.
Sevelamer does not significantly change circulating markers of microbial translocation. A, Serum lipopolysaccharide (LPS) levels measured 2–4 weeks before initiation of sevelamer treatment, on the day of initiating treatment, after 4 weeks of treatment, after 8 weeks of treatment, and 8 weeks after cessation of treatment (week 16). B, Plasma soluble CD14 (sCD14) levels measured 2–4 weeks before initiation of sevelamer treatment, on the day of initiating treatment, after 4 weeks of treatment, after 8 weeks of treatment, and 8 weeks after cessation of treatment (week 16). C, Sevelamer decreases plasma soluble tissue factor (sTF) levels, which rebound after treatment cessation. Levels were measured 2–4 weeks before initiation of sevelamer treatment, on the day of initiating treatment, after 4 weeks of treatment, after 8 weeks of treatment, and 8 weeks after cessation of treatment (week 16). D, Sevelamer reduces oxidized low-density lipoprotein cholesterol (oxLDL) levels. oxLDL levels were measured 2–4 weeks before initiation of sevelamer treatment, on the day of initiating treatment, after 4 weeks of treatment, after 8 weeks of treatment, and 8 weeks after cessation of treatment (week 16). Shading indicates treatment period. Thin lines represent individual subjects over time. Thick red lines represents the median values at each study week. P values were calculated using the sign test. Abbreviation: NS, not significant.

Source: PubMed

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