**6. HAART-associated lipodystrophy**

Lipodystrophy is a syndrome that includes peripheral fat wasting and central obesity and is a well-documented side effect of HAART (Table 3) [16, 53, 81]. In addition to the decrease in the expression of LDL receptors, and a consequent increase in serum concentrations of LDL, the most obvious mechanism of HAART-associated lipodystrophy and dyslipidemia are the mitochondrial changes induced by HAART [13, 62-64]. The inhibition of mtDNA-polymerase γ, which leads to mitochondrial DNA depletion in respiratory chain dysfunction and a reduced energy production in cells, may promote metabolic disorders in adipocytes and promote increased lipodystrophy syndrome and plasma lipid levels [62-64, 82, 83]. Both therapies, PIsand NRTIs-based, are associated with the inhibition of mtDNA-polymerase γ [82-84]. The abnormalities observed in lipodystrophy syndrome include lipoatrophy, lipohypertrophy, and metabolic disturbances. Lipoatrophy is associated with the loss of subcutaneous fat, usually in the lower limbs, face and buttocks. The observation of lipoatrophy in HIV-1 patients has been demonstrated in therapy with both PIs- and NRTIs-based therapies. Several studies initially suggested that lipoatrophy in HIV-1 patients is primarily associated with the use of PI-based therapies; however, more recent reports show that the incidence of lipoatrophy was significantly higher in the efavirenz plus two NRTIs group than in the lopinavir or efavirenz plus two NRTIs plus lopinavir groups [85-87]. The association of lipoatrophy with efavirenz use was mainly in combination with either stavudine or zidovudine but not with tenofovir/ lamivudine. Lipohypertrophy consists of the accumulation of adipose tissue. The PI-based therapy has been associated with the development of lipohypertrophy, but several longitudi‐ nal studies have failed to demonstrate that this therapy is the main cause of lipohypertrophy in HIV-1 patients [86-89].


**Table 2.** Antiretroviral drugs: impact on lipid and glucose metabolism.


**Table 3.** Clinical diagnosis and treatment of to HIV-associated lipodystrophy syndrome.
