Ezetimibe (Zetia) Reduces Bad LDL Cholesterol in HIV Positive People on HAART

By Liz Highleyman

Researchers have studied various strategies for managing metabolic complications such as abnormal blood lipid levels, insulin resistance, and body fat alterations (lipodystrophy) in HIV positive people receiving antiretroviral therapy.

In the October 15, 2008 issue of Clinical Infectious Diseases, David Wohl and colleagues described a study of the lipid-lowering medication ezetimibe (Zetia, Ezetrol) used as monotherapy in HIV positive individuals.

Ezetimibe lowers blood cholesterol levels by blocking cholesterol absorption in the intestine, whereas the statin class of drugs (also known as HMG-CoA reductase inhibitors) interfere with cholesterol production in the liver. Ezetimibe is often added to statins, but may also be used alone (for example, if an individual cannot tolerate a statin).

In the present study, 48 HAART-treated HIV positive patients with moderately elevated low-density lipoprotein (LDL or "bad") cholesterol at baseline (mean 128 mg/dL) were randomly assigned to receive 10 mg daily ezetimibe or placebo for 6 weeks. After a 2 week washout period, they then crossed over to the other arm for an additional 6 weeks.

Results

• The mean change in LDL cholesterol was -5.3% (-11 mg/dL) in patients taking ezetimibe, compared with +5.5% (+4 mg/dL) in those taking placebo (P = 0.04).

• Ezetimibe was associated with a 10.8% mean decrease in LDL cholesterol (P = 0.04).

• Ezetimibe was not associated with changes in high-density lipoprotein (HDL or "good") cholesterol or triglyceride levels.

• Ezetimibe was well tolerated, with no severe adverse events.

• 3 participants taking ezetimibe and 3 taking placebo discontinued therapy.

Based on these findings, the investigators concluded, "Ezetimibe was safe and effective in reducing low-density lipoprotein cholesterol and is an option for patients who cannot tolerate treatment with a statin."

The investigators described the magnitude of LDL reduction observed in this study as "meaningful," given that such decreases have been associated with lower risk of cardiovascular disease (1% decrease in cardiovascular risk per 1% reduction in LDL).

A small study of combination therapy using ezetimibe plus a low-dose statin in HIV positive people was reported earlier this year.

Ezetimibe monotherapy may be a preferred option for some individuals, however, for example due to the potential for statin interactions with antiretroviral drugs or concerns about statin-related liver toxicity in people with hepatitis B or C coinfection.

10/17/08

Reference
DA Wohl, D Waters, RJ Simpson, and others. Ezetimibe alone reduces low-density lipoprotein cholesterol in HIV-infected patients receiving combination antiretroviral therapy. Clinical Infectious Diseases 47(8): 1105-1108. October 15, 2008. (Abstract).