Human obesity and thinness, hyperlipidemia, hyperglycemia, and insulin resistance associated with HIV, protease inhibitors - Prevention by alternating several antiproteases in short sequences

In 1997, and mainly in 1998 and 1999, a lipodystrophic syndrome with centra l obesity, peripheral fat loss, hyperlipidemia, hyperglycemia and insulin-r esistant-diabetes II, was described as the most frequent manifestation of t oxicity of HIV1 virostatic therapy, associated with protease inhibitors (PI ) in 83% of the patients who used them for 10 months. Almost similar syndromes had been published before the latter, due, for exa mple, to graft vs host reaction, or autoimmunity against insulin receptors, or to caloric excess in the presence of androgens (the mediator being hype rinsulinemia). Carr and Cooper have presented an original pathophysiologica l mechanism for the PI-associated syndrome, residing in 63% homology betwee n HIV1-protease and the 3-low-density-lipoprorein-receptor-related protein (LRP), and in 53% homology between this virus enzyme and retinoid-binding-p rotein type 1 (CRAB1). The treatment should be more subtle than those of common obesity and/or typ e II diabetes. This HIV1-protease inhibitor toxicity can be prevented by al ternating several antiproteases in short sequences of the different ones. ( C) 1999 Editions scientifiques et medicales Elsevier SAS.