Influence of diet and genetics on metabolic abnormalities in mice treated with HIV protease inhibitors

Long-term therapy with HIV protease inhibitors (PIs) is associated with met abolic complications, such as lipodystrophy, obesity, dyslipidemia, and dia betes. The influence of diet and genetic background on the metabolic effect s of PIs was determined in AKR/J and SWR/J mice, which are susceptible and resistant to diet-induced obesity, respectively. The mice were maintained o n either a low- or high-fat diet and dosed for 2 weeks with various PIs and metabolic parameters measured. The results suggest that diet and genetic b ackground influence the effects of PIs on lipid and carbohydrate metabolism . Furthermore, the PIs altered metabolism to varying degrees (IDV greater t han or equal to NFV>SQV>APV), indicating the PIs may vary in potency, toxic ity and affect distinct mechanisms.