By Ronald Baker, PhD

Ezetimibe (Zetia) is an FDA-approved drug for reducing the level of cholesterol in the blood. Most frequently, physicians prescribe ezetimibe in combination with statins, the most commonly used class of cholesterol-lowering agents.

The statins include lovastatin (Mevacor), atorvastatin (Lipitor), simvastatin (Zocor), pravastatin (Pravachol), and rosuvastatin (Crestor). These drugs act by preventing the production of low-density lipoprotein (LDL or "bad") cholesterol by the liver. Ezetimibe has a different mechanism of action, lowering blood levels of LDL cholesterol by reducing the absorption of cholesterol from the intestine. It does not affect the absorption of triglycerides or fat-soluble vitamins.

Potential Statin Toxicity

A potential adverse effect of the statins is myopathy (inflammation of muscle tissue). Statins differ in the frequency with which they cause a severe type of myopathy called rhabdomyolysis, in which muscles are severely damaged.

The Current Study

The safety and efficacy of ezetimibe in HIV positive patients is unknown. Researchers at the University of North Carolina, Chapel Hill and the University of California, San Francisco presented data last week at the 14th Conference on Retroviruses and Opportunistic Infections in Los Angeles suggesting that ezetimibe may be used to reduce elevated LDL cholesterol in HIV positive patients, including in those who cannot tolerate statins.

The present study was a randomized, double-blind, placebo-controlled trial to assess the safety and effectiveness of ezetimibe in lowering LDL cholesterol in HIV positive individuals on stable HAART. Study participants were not taking any lipid-lowering medications and had LDL cholesterol levels ? 75 mg/dL and triglyceride levels < 800 mg/dL.

Participants were randomized to receive 10 mg daily ezetimibe or placebo for 6 weeks, followed by a 2-week washout period, then crossing over for 6 weeks of treatment with the alternative therapy. Fasting lipid panels (8 hours) including direct LDL cholesterol and blood chemistries were evaluated at study entry and at weeks 6, 8, and 14.
Results:

• 48 study participants were enrolled (23% women; 48% African American).

• Median age was 46 years, median CD4 cell count was 555 cells/mm3, and all but 1 subject had HIV RNA < 400 copies/mL.

• 25 patients were randomized to ezetimibe followed by placebo, while 23 received placebo followed by ezetimibe.

• At pre-intervention and following the washout period, the median LDL cholesterol levels were 121 mg/dL and 123 mg/dL, respectively (P = 0.70).

• The median percentage change in LDL cholesterol was -12% after ezetimibe treatment, and 3% after placebo (P = 0.03).

• 35% of patients had at least a 17% drop in LDL cholesterol after 6 weeks on ezetimibe.

• The difference in percentage change in LDL cholesterol comparing ezetimibe to placebo was -12% (P = 0.02).

• Treatment period did not affect these results (P = 0.85).

• There were no significant changes in high-density lipoprotein (HDL or "good") cholesterol or triglyceride levels.

• Of the 5 subjects who discontinued the study prematurely, 2 were on ezetimibe (1 grade 3 liver function test [LFT] abnormality in a subject with grade 1 LFT abnormality at entry, 1 epigastric pain) vs 3 on placebo (1 grade 2 LFT abnormality, 1 headache and nausea, 1 neuropathy).

• 2 other subjects had new LFT increases (grade 2), both while on placebo.

Conclusion

"Ezetimibe alone led to significant and clinically meaningful declines in LDL cholesterol and was well-tolerated," concluded the investigators.

They emphasized that this was the first placebo-controlled study of ezetimibe in HIV positive patients. They noted that these study results suggest a role for the drug in the management of elevated LDL cholesterol in patients with HIV.

Finally, the researchers pointed out that for patients unable to take a statin, "monotherapy with ezetimibe may be an option."

03/09/07

Reference
D Wohl, P Hsue, S Richard, and others. Ezetimibe's Effects on the LDL Cholesterol Levels of HIV-infected Patients Receiving HAART. 14th Conference on Retroviruses and Opportunistic Infections. Los Angeles. February 25-28, 2007. Abstract 39 (oral).

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