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The use of highly active antiretroviral therapy (HAART) has extremely enhanced the clinical outcome of HIV disease with a decrease in mortality and morbidity. However, the inclusion of protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (tNRTIs) has strongly been linked to the development of metabolic abnormalities and lipodystrophy. Lipodystrophy is defined by the loss of peripheral subcutaneous fat and central adiposity, mainly in the abdomen, breast and dorsocervical region. These disorders are reported to be cosmetically distressing and socially stigmatizing to many patients leading to decreased adherence to antiretroviral therapy. Metabolic syndrome precedes lipodystrophy leading to increased risk of diabetes and cardiovascular diseases. With a shifted trajectory of HIV/AIDS morbidity from immunodeficiency and opportunistic infections to metabolic complications, clinical management of these patients has therefore become more complex. Currently there are no evidence-based standard guidelines for the management of HIV-associated lipodystrophy. Several pharmacological interventions such as using anti-diabetic, anti-dyslipidemic drugs or hormone replacement therapy have been tried to effectively improve metabolic syndrome and lipodystrophy but have been hampered by low efficacy, drug interactions, or unwanted side-effects. Non-pharmacological interventions including surgical manipulations, dietary and lifestyle modifications have also been tried with limited success. This review focuses on the proposed mechanisms involved in the development of metabolic syndrome and lipodystrophy, and highlights suggested potential therapeutic interventions to prevent lipodystrophy associated with HAART.

BackgroundInsulin resistance, glucose intolerance and overt diabetes are known metabolic complications associated with chronic use of HIV-Protease Inhibitors. Naringin is a grapefruit-derived flavonoid with anti-diabetic, anti-dyslipidemia, anti-inflammatory and anti-oxidant activities.ObjectivesThe study investigated the protective effects of naringin on glucose intolerance and impaired insulin secretion and signaling in vivo.MethodsMale Wistar rats were divided into six groups (n = 6) and were daily orally treated with distilled water {3.0 ml/kg body weight (BW)}, atazanavir (133 mg/kg BW), saquinavir (333 mg/kg BW) with or without naringin (50 mg/kg BW), respectively for 56 days. Body weights and water consumption were recorded daily. Glucose tolerance tests were carried out on day 55 of the treatment and thereafter, the rats were sacrificed by halothane overdose.ResultsAtazanavir (ATV)- or saquinavir (SQV)-treated rats exhibited significant weight loss, polydipsia, elevated Fasting blood glucose (FBG), reduced Fasting Plasma Insulin (FPI) and expression of phosphorylated, Insulin Receptor Substrate-1 (IRS-1) and Akt proteins, hepatic and pancreatic glucokinase levels, and also increasing pancreatic caspase-3 and -9 as well as UCP2 protein expressions compared to controls, respectively. These effects were completely reversed by naringin treatment.ConclusionNaringin prevents PI-induced glucose intolerance and impairment of insulin signaling and as nutritional supplement it could therefore alleviate metabolic complications associated with antiretroviral therapy.

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