Adverse metabolic disorders during highly active antiretroviral treatments(HAART) of HIV disease

Protease inhibitor treatment has dramatically improved rates of morbidity a nd mortality in HIV-infected patients. However, it has recently been shown that this medication is associated with longterm side effects characterized by metabolic, clinical and biological alterations. These modifications hav e been described in patients treated with highly active antiretroviral ther apy (HAART), including nucleoside analogue reverse transcriptase inhibitors (NRTI) and generally (but not always) protease inhibitors (PI). Clinical a lterations are characterised by a body fat redistribution syndrome or lipod ystrophy, with peripheral lipoatrophy and/or central fat accumulation. They are often associated with biological alterations, i.e. insulin resistance, hyperglycaemia and dyslipidaemia, which can also be observed alone. The pa thophysiology of these alterations is presently unknown. The deleterious ef fect of PI on adipose tissue could be direct or indirect, and is probably m odulated by genetic or environmental factors. NRTI could also be involved b ecause of their mitochondrial toxicity. The purpose of the treatment is to control metabolic disturbances in order to prevent immediate complications such as acute pancreatitis and limit possible cardiovascular and diabetic c omplications at longer term. Studies are in progress to evaluate the possib ility of therapeutic alternatives to PI when major metabolic disturbances a re present.