Involvement of the LPS-LPB-CD14-MD2-TLR4 inflammation pathway in HIV-1/HAART-associated lipodystrophy syndrome (HALS).

Abstract

OBJECTIVES:

A relationship between obesity and intestinal bacterial translocation has been reported. Very little information is available with respect to the involvement of the bacterial translocation mechanistic pathway in HIV-1/highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (HALS). We determined whether lipopolysaccharide (LPS)-binding protein (LBP), cluster of differentiation 14 (CD14), myeloid differentiation protein 2 (MD2) and toll-like receptor 4 (TLR4) single-nucleotide polymorphisms and LPS, LBP and soluble CD14 (sCD14) plasma levels are involved in HALS.

PATIENTS AND METHODS:

This cross-sectional multicentre study involved 558 treated HIV-1-infected patients, 240 with overt HALS and 318 without HALS. Anthropometric, clinical, immunovirological and metabolic variables were determined. Polymorphisms were assessed by genotyping. Plasma levels were determined by ELISA in 163 patients (81 with HALS and 82 without HALS) whose stored plasma samples were available. Student's t-test, one-way ANOVA, two-way repeated measures ANOVA, the χ(2) test and Pearson and Spearman correlation analyses were carried out for statistical analysis.

RESULTS:

LBP rs2232582 T→C polymorphism was significantly associated with HALS (P = 0.01 and P = 0.048 for genotype and allele analyses, respectively). Plasma levels of LPS (P = 0.009) and LBP (P < 0.001) were significantly higher and sCD14 significantly lower (P < 0.001) in patients with HALS compared with subjects without HALS. LPS levels were independently predicted by triglycerides (P < 0.001) and hepatitis C virus (P = 0.038), LBP levels by HALS (P < 0.001) and sCD14 levels by age (P = 0.008), current HIV-1 viral load (P = 0.001) and protease inhibitor use (P = 0.018).

CONCLUSIONS:

HALS is associated with LBP polymorphism and with higher bacterial translocation.

• Authors: Consuelo Viladés, Xavier Escoté, Miguel López-Dupla, Esteban Martinez, Pere Domingo, Víctor Asensi, Manuel Leal, Joaquim Peraire, Maria-Isabel Inza, Mireia Arnedo, Mar Gutiérrez, Eulalia Valle-Garay, Sara Ferrando-Martinez, Montserrat Olona, Verónica Alba, Joan-Josep Sirvent, Josep M Gatell, Francesc Vidal, HALS Study Group
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 69 Issue 6 Pg. 1653-9 (Jun 2014) ISSN: 1460-2091 [Electronic] England
• PMID: 24535275 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• Acute-Phase Proteins
• Carrier Proteins
• Lipopolysaccharide Receptors
• Lipopolysaccharides
• Lymphocyte Antigen 96
• Membrane Glycoproteins
• Toll-Like Receptor 4
• lipopolysaccharide-binding protein

Topics

• Acute-Phase Proteins (genetics, metabolism)
• Adult
• Antiretroviral Therapy, Highly Active (adverse effects)
• CD4 Lymphocyte Count
• Carrier Proteins (blood, genetics, metabolism)
• Case-Control Studies
• Cross-Sectional Studies
• Female
• HIV Infections (complications, drug therapy, immunology, virology)
• HIV-1
• HIV-Associated Lipodystrophy Syndrome (diagnosis, etiology, metabolism)
• Humans
• Inflammation
• Lipopolysaccharide Receptors (blood, genetics, metabolism)
• Lipopolysaccharides (blood, immunology)
• Lymphocyte Antigen 96 (genetics, metabolism)
• Male
• Membrane Glycoproteins (blood, genetics, metabolism)
• Middle Aged
• Risk Factors
• Signal Transduction
• Toll-Like Receptor 4 (genetics, metabolism)
• Viral Load