Lipid-lowering and anti-inflammatory effects of tetradecylthioacetic acid in HIV-infected patients on highly active antiretroviral therapy

Eur J Clin Invest. 2004 Oct;34(10):709-15. doi: 10.1111/j.1365-2362.2004.01410.x.

Abstract

Background: Highly active antiretroviral therapy (HAART) often leads to a dramatic improvement in clinical, viral and immunologic parameters in HIV-infected individuals. However, the emergence of long-term side-effects of HAART and in particular dylipidaemia is increasingly reported. Based on the potential lipid-lowering and immunomodulatory properties of tetradecylthioacetic acid (TTA) we examined whether TTA in combination with dietary intervention could modify lipid levels in peripheral blood in HIV-infected patients on HAART.

Materials and methods: Ten HIV-infected patients on protease inhibitor-based HAART with hyperlipidaemia followed a cholesterol-lowering diet throughout the study period (8 weeks). During the last 4 weeks of the study all patients received TTA (1 g qd) in addition to the cholesterol-lowering diet.

Results: Our main and novel findings were: (i) TTA in combination with dietary intervention reduces total cholesterol, LDL cholesterol, triglycerides and LDL/HDL cholesterol in these patients, and a particularly suppressing effect was observed during the TTA phase regarding total cholesterol. (ii) During the TTA phase, the cholesterol-lowering effect was accompanied by a significant reduction in plasma levels of tumour necrosis factor alpha. (iii) Our studies in peripheral blood mononuclear cells from these patients and in the liver from wild-type mice receiving TTA suggest that the hypolipidaemic effects of TTA may involve up-regulation of scavenger and LDL-receptor expression.

Conclusions: Although few patients were studied, the present pilot study suggests that TTA combined with dietary intervention could be an interesting therapeutic approach in HIV-infected patients on HAART, potentially resulting in both hypolipidaemic and anti-inflammatory effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Female
  • HIV Infections / blood
  • HIV Infections / diet therapy
  • HIV Infections / drug therapy*
  • Humans
  • Hyperlipidemias / drug therapy*
  • Hypolipidemic Agents / therapeutic use*
  • Insulin Resistance
  • Leukocytes, Mononuclear
  • Lipids / blood
  • Male
  • Mice
  • Middle Aged
  • Pilot Projects
  • Receptors, Immunologic / metabolism
  • Receptors, Scavenger
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sulfides / therapeutic use*
  • Up-Regulation

Substances

  • Anti-Inflammatory Agents
  • Hypolipidemic Agents
  • Lipids
  • Receptors, Immunologic
  • Receptors, Scavenger
  • Sulfides
  • 1-(carboxymethylthio)tetradecane