Effect of DHA on Lipid and Carbohydrate Metabolism Alterations and Body Fat Distribution in HIV Patients Under HAART.
Status:
Completed
Trial end date:
2013-10-01
Target enrollment:
Participant gender:
Summary
Highly active antiretroviral therapy (HAART) is able to cause lipid metabolism and glucose
homeostasis alterations, which are associated to the redistribution of body fat. Alterations
in lipid and carbohydrate metabolism contribute to the development of a highly atherogenic
profile, which together with altered fibrinolysis markers and increased presence of
proinflammatory cytokines in blood (especially tumor necrosis factor alpha) that comes
associated to the success of HAART can cause the development of accelerated atherosclerosis.
Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid that has demonstrated its ability
to reduce triglyceride levels; modify cholesterol fractions and increase the size of LDL
particles thereby configuring less atherogenic plasma profile. Additionally, administration
of DHA has shown antiinflammatory and hypotensive activity, which contributes to reduce the
risk of cardiovascular complications in these patients. At a molecular level, DHA acts as a
stimulator of the nuclear receptor PPAR-gamma, which has been described to induce an increase
in adipocyte differentiation. Furthermore, the anti-inflammatory effects induced by DHA, can
decrease the elevated levels of TNF-alpha, which has been implicated in the pathogenesis of
body fat redistribution in HIV infected patients undergoing HAART. Therefore, the hypothesis
of this project is that DHA will be able to produce lipid-lowering, anti-inflammatory,
hypotensive and profibrinolytic effects, which all together should improve atherogenic
profile of patients with HIV-1 infection receiving HAART. In addition, their proprieties as
PPAR agonist can improve the redistribution of body fat present in many of these patients.
The study of the activity of DHA on dendritic cells and monocytes should indicate the absence
of immunosuppressive effect of DHA in the context of HIV-1 infection.
In summary, DHA is a natural product, from the omega 3 polyunsaturated fatty acids, the
therapeutic properties of which have been described in recent years and has shown
cardio-vascular and metabolic beneficial effects, without recognized side effects. The highly
purified DHA administration at high doses could be able to reverse, at least partially, lipid
abnormalities associated with HAART and to exert a beneficial effect on fat redistribution in
HIV-infected patients treated with HAART. To ensure non deleterious immunological treat in
these sensitive poly-medicated patients, substantial changes in the functionality of
dendritic cells and monocytic will be studied.
Phase:
Phase 3
Details
Lead Sponsor:
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Collaborators:
Hospital Clinic of Barcelona University of Barcelona