Hyperlipidemia related to the use of HIV-protease inhibitors: natural history and results of treatment with fenofibrate

Hyperlipidemia has been frequently recorded as a side effect of treating HIV patients with protease inhibitors (PI). This study was initiated to analyze the modifications on blood lipids in HIV-patients receiving PI and the safety and efficacy of the treatment with fenofibrate. Total (TC) and HDL-cholesterol, triglycerides (TG), and CD(4)(+) T-cell counts were measured in 30 HAART-naive patients (Group I) before and after PI introduction. In a second phase of the study, the effects of fenofibrate on lipids, CPK, CD(4)(+), and viral load were determined in 13 patients (Group II) with elevated TC or TG. In Group I, 60 of the patients showed TC or TG elevations. Average increments of 31 and 146 in TC and TG respectively (p<0.0006 and p<0.0001) were observed. In Group II, fenofibrate treatment was associated with decrements of 6.6 (TC) and 45.7 (TG) (p=0.07 and 0.0002) and no modifications on CPK, CD(4)(+), and viral load. In conclusion, hyperlipidemia is common during the treatment of HIV with protease inhibitors, and fenofibrate appears to be an effective and safe choice for its treatment.

The lipoprotein profile in HIV infected patients

Infection can change plasma lipoproteins by increasing the triglycerides and decreasing the cholesterol plasma levels. This process is thought to be result of alterations in lipoprotein metabolism produced by cytokines that mediate the immune response, including tumor necrosis factor, interleukin-1 and the interferons. The acquired immunodeficiency syndrome (AIDS) has been shown to accompanied by increased plasma triglyceride levels and a trend toward decreased plasma cholesterol levels. Plasma low density lipoprotein (LDL) patterns are also changed by infection and patients with AIDS have increased levels of small dense particles. Decreases in high density lipoprotein cholesterol (HDL-C) and apoliprotein A-I, and an increase in lipoprotein (a) [Lp(a)] are the usual lipidic disorders during HIV infection, even in those patients with CD4 lynphocyte counts above 400 cells/mmü. Plasma lipoproteins possess well-recognized transport functions. Certain classes of these lipoproteins can also regulate selected metabolic functions of a variety of cell types. Among these bioregulatory properties is the regulation of lymphocyte function and regulation of immune response. Thus, a number of immune functions may be significantly influenced by the lipoprotein alterations present in AIDS. Furthermore, the decreased HDL-C and increased triglycerides and Lp(a) are associated with an increased risk of myocardial infarction and some cardiovascular events have been reported in HIV positive individuals. This paper describes lipoprotein alterations during HIV infection, and evaluates their relationship to immune function and atherogenic profile