Do We Know the Underlying Mechanism of Lipodystrophy?
The hope is, of course, that an understanding of the mechanism of PI-associated metabolic defects may allow drug companies to either design drugs that avoid these complications altogether or at least screen for impact on lipid metabolism in the preclinical stages of drug development. However, that understanding remains elusive. Lenhard demonstrated that NFV, RTV, SQV could inhibit in vitro lipid accumulation by stimulating lipolysis and inhibiting lipogenesis and seemed to operate by a specific effect on nuclear receptors (peroxisome proliferator activated receptor, or PPAR; and retinoid X receptor, or RXR) [Abstracts 665, 666]. IDV and amprenavir did not demonstrate this effect, though IDV did stimulate retinoid signaling through a second gene, alkaline phosphatase. Did We Learn Anything New in Chicago About Metabolic Complications that Will Change the Way We Practice? Highly effective PI-sparing regimens now make it possible for a patient to switch off of a PI and still maintain good
