HIV-1/HAART-Related Lipodystrophy Syndrome (HALS) Is Associated with Decreased Circulating sTWEAK Levels

PLoS One. 2015 Dec 14;10(12):e0144789. doi: 10.1371/journal.pone.0144789. eCollection 2015.

Abstract

Background and objectives: Obesity and HIV-1/HAART-associated lipodystrophy syndrome (HALS) share clinical, pathological and mechanistic features. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine that plays an important role in obesity and related diseases. We sought to explore the relationship between HALS and circulating levels of soluble (s) TWEAK and its scavenger receptor sCD163.

Methods: This was a cross-sectional multicenter study of 120 HIV-1-infected patients treated with a stable HAART regimen; 56 with overt HALS and 64 without HALS. Epidemiological and clinical variables were determined. Serum levels of sTWEAK and sCD163 levels were measured by ELISA. Results were analyzed with Student's t-test, Mann-Whitney U and χ2 test. Pearson and Spearman correlation were used to estimate the strength of association between variables.

Results: Circulating sTWEAK was significantly decreased in HALS patients compared with non-HALS patients (2.81±0.2 vs. 2.94±0.28 pg/mL, p = 0.018). No changes were observed in sCD163 levels in the studied cohorts. On multivariate analysis, a lower log sTWEAK concentration was independently associated with the presence of HALS (OR 0.027, 95% CI 0.001-0.521, p = 0.027).

Conclusions: HALS is associated with decreased sTWEAK levels.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antigens, CD / blood
  • Antigens, CD / genetics
  • Antigens, Differentiation, Myelomonocytic / blood
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Antiretroviral Therapy, Highly Active
  • Cross-Sectional Studies
  • Cytokine TWEAK
  • Female
  • Gene Expression
  • HIV-1 / physiology
  • HIV-Associated Lipodystrophy Syndrome / blood*
  • HIV-Associated Lipodystrophy Syndrome / diagnosis
  • HIV-Associated Lipodystrophy Syndrome / drug therapy*
  • HIV-Associated Lipodystrophy Syndrome / genetics
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Receptors, Cell Surface / blood
  • Receptors, Cell Surface / genetics
  • Tumor Necrosis Factors / blood*
  • Tumor Necrosis Factors / genetics

Substances

  • Anti-HIV Agents
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • Cytokine TWEAK
  • Receptors, Cell Surface
  • TNFSF12 protein, human
  • Tumor Necrosis Factors

Grants and funding

This work has been partially financed by grants from: Fondo de Investigacion Sanitaria (PI10/2635, PI11/02512, PI11/0376, PI13/0796 and 14/0465); Instituto de Salud Carlos III. Ministerio de Sanidad, Política Social e Igualdad (EC11-293); Fundación para la Investigación y Prevención del Sida en España (FIPSE 06/36572 and 06/36610); Gilead Fellowship Program (GD14-293); Programa de Suport als Grups de Recerca AGAUR (2014SGR250); Red de Investigación en Sida (RIS): RIS-EST29 and RD12/0017/0001, RD12/0017/0005, RD17/0017/0022 and RD17/0017/0029; Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo en Innovación Tecnológica 2008-2001; Instituto de Salud Carlos III, Fondos Europeos para el Desarrollo Regional (FEDER). FV and PD are supported by a grant from the Programa de Intensificación de Investigadores, Instituto de Salud Carlos III (INT11/240, INT12/282 and INT12/383). MA is supported by the Instituto de Salud Carlos III and the Departament de Salut de la Generalitat de Catalunya. MRC is supported by the Research Stabilization Programme of the Instituto de Salud Carlos III (ISCIII) co-financed by Institut Català de Salut (ICS) in Catalonia.