Rosuvastatin Decreases Intestinal Fatty Acid Binding Protein (I-FABP), but Does Not Alter Zonulin or Lipopolysaccharide Binding Protein (LBP) Levels, in HIV-Infected Subjects on Antiretroviral Therapy.

Morgan Boucher,Nicholas Funderburg,Abdus Sattar,Bruce I Kinley,Danielle Labbato,Grace A Mccomsey,Manjusha Kulkarni

doi:10.20411/pai.v1i1.124

Abstract

Introduction:Altered gastrointestinal (GI) barrier integrity and subsequent microbial translocation may contribute to immune activation in HIV infection. We have reported that rosuvastatin improved several markers of immune activation in HIV+ participants, but the effect of statin treatment on markers of GI barrier dysfunction is unknown.Methods:SATURN-HIV is a randomized, double-blind, placebo-controlled trial assessing the effect of rosuvastatin (10mg/daily) on markers of cardiovascular disease, inflammation, and immune activation in ART-treated patients. Gut-barrier integrity was assessed by the surrogate markers intestinal fatty acid binding protein (I-FABP), a marker of enterocyte death, and zonulin-1, a marker of gut epithelial cell function. Levels of lipopolysaccharide binding protein (LBP) were measured as a marker of microbial translocation.Results:Rosuvastatin significantly reduced levels of I-FABP during the treatment period compared to the placebo. There was no effect of rosuvastatin treatment on levels of zonulin or LBP. Baseline levels of LBP were directly related to several markers of immune activation in samples from all participants, including soluble CD163, IP-10, VCAM-1, TNFR-II, and the proportion of CD4+ and CD8+ T cells expressing CD38 and HLA-DR. Many of these relationships, however, were not seen in the statin arm alone at baseline or over time, as inflammatory markers often decreased and LBP levels were unchanged.Conclusions:Forty-eight weeks of rosuvastatin treatment reduced levels of I-FABP, but did not affect levels of zonulin or LBP. The reduction in levels of inflammatory markers that we have reported with rosuvastatin treatment is likely mediated through other mechanisms not related to gut integrity or microbial translocation.SATURN-HIV is registered on clinicaltrials.gov; Identifier: NCT01218802

Highlights

Altered gastrointestinal (GI) barrier integrity and subsequent microbial translocation may contribute to immune activation in HIV infection
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, have anti-inflammatory effects [5, 6], and within the Stopping Atherosclerosis and Treating Unhealthy bone with RosuvastatiN in HIV (SATURN-HIV) trial, we have reported significant reductions in monocyte and T-cell activation (CD38 and HLA-DR on CD4+ and CD8+ cells) and vascular inflammation following initiation of statin therapy [7,8,9]
We measured plasma levels of intestinal fatty acid binding protein (I-FABP), a marker of enterocyte death [20], zonulin-1, a marker of enterocyte function [21], and lipopolysaccharide binding protein (LBP), in order to determine whether the effect of statin therapy on reducing immune activation is mediated by improvement of GI integrity and reduction of microbial translocation

Summary

Introduction

Altered gastrointestinal (GI) barrier integrity and subsequent microbial translocation may contribute to immune activation in HIV infection. We have reported that rosuvastatin improved several markers of immune activation in HIV+ participants, but the effect of statin treatment on markers of GI barrier dysfunction is unknown. There are likely multiple contributors to immune activation in ART-treated HIV infection, including: low level HIV-1 replication [10]; copathogens [11]; pro-inflammatory lipids (e.g., oxidized LDL) [12, 13]; and microbial translocation [14]. We measured plasma levels of I-FABP, a marker of enterocyte death [20], zonulin-1, a marker of enterocyte function [21], and lipopolysaccharide binding protein (LBP), in order to determine whether the effect of statin therapy on reducing immune activation is mediated by improvement of GI integrity and reduction of microbial translocation

Methods

Results

Discussion

Conclusion