LDL-receptors expression in HIV-infected patients: relations to antiretroviral therapy, hormonal status, and presence of lipodystrophy

Background Abnormalities in lipid levels and lipodystrophy (LD) have been commonly reported after commencement of highly active antiretroviral therapy (HAART). A major mechanism by which plasma low-density lipoprotein (LDL) cholesterol levels may be influenced is via the regulation of hepatic LDL receptor expression. The activity of LDL receptors is under hormonal control. Moreover, HIV infection and HAART are associated with important modifications of hormonal status. As the cause of these adverse reactions is unknown, the effects of HAART and lipodystrophy on LDL receptors were evaluated. Materials and methods Thirty-nine HIV treated patients (21 with a protease inhibitor (PI) containing regimen, 18 without PI use) and 22 control subjects were tested for insulin resistance (HOMA model assessment), lipid profile, serum concentration of dehydroepiandrosterone (DHEA) and LDLR expression. LDL-R on mononuclear cells were quantified by flow cytrometry. Results Among the 39 HIV infected patients, 14 patients had a lipodystrophy (LD). Patients with LD had significantly higher levels of triglyceride (TG) and insulin resistance compared to patients without I-D. There was no significant difference in LDL-R count between patients with or without PI use. In contrast, LDLR count was significantly lower in patients with LD compared with those without (8504 +/- 3901 vs. 13 200 +/- 4532, P=0.001). There was no difference in LDLR count between patients without LD and control subjects. Patients with LD had lower levels of DHEA compared to patients without LD. In HIV-infected patients, we found a significant correlation between LDL-R expression and TG (r = -0.32; P = 0.04) and LDL cholesterol (r = -0.33; P = 0.04). In contrast, we did not observe a correlation between DHEA level and LDL-R count or LDL cholesterol level. Conclusions HIV-lipodystrophy is associated with a lower expression of LDL-R. This decreased expression of LDL-R seems independent of DHEA or insulin secretion.