HIV protease inhibitors and dyslipidemia.
Highly active antiretroviral therapy (HAART) significantly prolongs the lives of HIV-infected patients. Current regimens may consist of a protease inhibitor (PI) combined with at least two or more other antiretroviral drugs. PI administration has been shown to be associated with alterations in plasma lipids (i.e. prompt and sustained increases in total cholesterol, low-density lipoprotein cholesterol, and triglycerides) and insulin levels that place PI-treated patients at risk for coronary heart disease (CHD). Because PI-associated dyslipidemia is generally asymptomatic and occurs in patients who are often younger than those traditionally at risk for CHD, the need for primary prevention of acute coronary events in these patients is often unappreciated. Statins form a significant component of pharmacotherapy for PI-associated dyslipidemia. However, because PIs and all statins except pravastatin are metabolized by the cytochrome P450 (CYP) system, co-administration of these agents produces a significant risk of drug interactions and statin-induced hepatotoxicity and myopathy. This risk can be greatly reduced by administering a statin not metabolized by CYP. The need for lipid reduction therapy may be minimized with the use of new PIs that are comparable in efficacy to current PIs but do not negatively affect lipid levels.
Clotet
Bonaventura
B
HIV Unit and Retrovirology Laboratory, IrsiCaixa Foundation, Hospital Universitari, Germans Trias i Pujol, Carretera del Canyet s/n Badalona, Barcelona, Spain. bclotet@ns.hugtip.scs.es
Negredo
Eugènia
E
D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use; D000069059:Atorvastatin; D004347:Drug Interactions; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects; D006538:Heptanoic Acids / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D006949:Hyperlipidemias / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008148:Lovastatin / Q000009:adverse effects / Q000627:therapeutic use; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D006538:Heptanoic Acids; D000960:Hypolipidemic Agents; D011758:Pyrroles; D018894:Reverse Transcriptase Inhibitors; D008148:Lovastatin; D000069059:Atorvastatin; D019821:Simvastatin