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Highly active antiretroviral therapy (HAART) has dramatically improved the prognosis of HIV-positive patients. However, long-term adverse effects of this therapy include dyslipidemia, insulin resistance (IR), changes in body fat distribution (lipodystrophy), and cardiometabolic syndrome (CMS). IR in HIV-positive patients does not seem to represent a significant independent risk factor for the development of cardiovascular disease; nevertheless, the association with other metabolic complications (dyslipidemia, fat redistribution) and CMS may increase the risk of type 2 diabetes and cardiovascular disease. The use of nucleoside analogue reverse transcriptase inhibitors is associated with the development of upper trunk and visceral fat accumulation and may cause IR. The progression of IR toward diabetes may be impeded with the choice of HAART regimens with less IR effects and encouraging patients to adhere to a healthy lifestyle. For patients with marked IR but relatively preserved fat, the use of metformin may consent the improvement of CMS and lipodystrophy, especially when combined with an appropriate exercise program. Therapy with rosiglitazone is not indicated in these patients.