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


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.
Rikshospitalet, Oslo, Norway.
J
J
Fredriksen
T
T
Ueland
E
E
Dyrøy
B
B
Halvorsen
K
K
Melby
L
L
Melbye
B S
BS
Skalhegg
P
P
Bohov
J
J
Skorve
R K
RK
Berge
P
P
Aukrust
S S
SS
Frøland
D000328:Adult; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000178:diet therapy / Q000188:drug therapy*; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D007963:Leukocytes, Mononuclear; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008875:Middle Aged; D010865:Pilot Projects; D011971:Receptors, Immunologic / Q000378:metabolism; D051116:Receptors, Scavenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013440:Sulfides / Q000627:therapeutic use*; D015854:Up-Regulation
D000893:Anti-Inflammatory Agents; D000960:Hypolipidemic Agents; D008055:Lipids; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D013440:Sulfides; C062078:1-(carboxymethylthio)tetradecane