**5. Mechanism of HAART-associated lipid disorders**

HAART-associated dyslipidemia is complex and involves immunological, hormonal, genetic predisposition aspects and the effects induced by different antiretroviral drugs [13, 47]. The observed dyslipidemia is characterized by hypertriglyceridemia, hypercholesterolemia, and decreased serum levels of HDL, either accompanied or unaccompanied by increased levels of LDL (Table 2) [47, 48]. Other metabolic and/or clinical common disorders include insulin resistance with hyperinsulinemia, increased C-peptide levels, diabetes mellitus and lipodys‐ trophy syndrome [44-48]. Diabetes mellitus is a group of metabolic disorders in which the blood glucose is higher than normal levels due to insufficiency of insulin release or improper response of cells to insulin. The resultant hyperglycemia produces sever complications [49]. The production and secretion of insulin is realized by pancreatic β-cells, and occurs in response to concentrations of amino acids, fatty acid and glucose. However, glucose is considered the first stimulus to the beta cells which secrete insulin. Regulated insulin release requires tight coupling in the β-cell between glucose metabolism and insulin secretory response [50]. HAART also affects the hydrolysis of TG-rich lipoproteins and tissue lipase, disrupts normal postprandial FFA and lipoprotein catabolism and interferes with peripheral fatty acid trapping. These effects could be due to the interaction of fatty acids with the master transcrip‐ tional regulator sterol regulatory element binding protein 1 (SREBP1) [51-56]. Nevertheless, the presence of dyslipidemia in individuals who use HAART is not necessarily accompanied by lipodystrophy and/or an evident insulin resistance, which suggests that the mechanism(s) involved in these disorders maybe independent [47, 51, 56, 57]. The NNRTI-based HAART, zidovudine, stavudine or lamivudine, has eventually become associated with the occurrence of dyslipidemia; however, lipid metabolism disorders are mainly evident in individuals who make use of the PI-based therapy [47, 48, 57, 58]. In as much as the mechanisms involved in PI-associated dyslipidemia are not fully understood, the prevailing hypothesis is based on the structural similarity between the catalytic region of the HIV-1 protease and two homologous human proteins involved in the metabolism of lipids, called cytoplasmic retinoic acid-binding protein type 1 (CRABP-1) and low-density lipoprotein-receptor-related protein type 1 (LRP1).
