Investigating the cellular targets of HIV protease inhibitors: implications for metabolic disorders and improvements in drug therapy.
The use of HIV protease inhibitors (PIs) may be associated with serious adverse side effects that include fat tissue redistribution, hyperlipidemia, and insulin resistance. The etiology of this toxic metabolic syndrome (commonly referred to as 'HIV lipodystrophy syndrome') remains to be elucidated. The interpretation of available clinical data on this subject is complicated in part by the pervasiveness of potential confounding factors that cannot be easily eliminated or adequately controlled. Numerous investigators have examined the effects of PIs on cellular processes in model systems amenable to extensive experimental manipulations; the present review primarily focuses on these efforts. The ultimate goal is the unambiguous identification of discrete cellular targets being surreptitiously impacted by PIs. SREBP and Glut4 are discussed as candidate target molecules in this context. The identification of cellular factors interacting with PIs represents a necessary first step in devising rational strategies for improvement in drug therapy.
Murata
H
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Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Hruz
P W
PW
Mueckler
M
M
D017667:Adipocytes / Q000187:drug effects; D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000139:chemically induced; D007333:Insulin Resistance / Q000502:physiology; D008659:Metabolic Diseases / Q000139:chemically induced* / Q000473:pathology
D017320:HIV Protease Inhibitors