Preliminary clinical trial results from a study indicate that Zetia® (ezetimibe) may be a moderately effective cholesterol-lowering option for HIV-positive patients receiving antiretroviral therapy. The new data, reported at the 14th Conference on Retroviruses and Opportunistic Infections today in Los Angeles, indicate that Zetia may be a useful option in HIV-positive patients, but also suggest that its effects may be somewhat limited.
Unlike statins (HMG-CoA reductase inhibitors), designed to block the action of an enzyme in the liver responsible for producing cholesterol, Zetia inhibits absorption of cholesterol by the intestine (duodenum). In clinical trials involving HIV-negative volunteers, Zetia was found to reduce "bad" LDL cholesterol by 20% when used without other lipid-lower medications and by approximately 50% when used with a statin.
Until recently, little has been known about the safety and effectiveness of Zetia in HIV-positive patients receiving antiretroviral therapy.
A 14-week study conducted by researchers at the University of North Carolina, Chapel Hill, and the University of California, San Francisco, enrolled 48 HIV-positive patients – all of whom were receiving antiretroviral therapy with moderately elevated “bad” LDL cholesterol levels. The average LDL cholesterol level was 121 mg/dL at the time of study entry (levels above 115 mg/dL are considered elevated).
In the first phase of the study, patients were randomized to Zetia (10 mg/day) or placebo for six weeks. This was followed by a two-week “washout period” in which no treatment was given. After the two-week washout period, those originally randomized to Zetia took six weeks of placebo treatment, and those originally randomized to placebo took six weeks of Zetia treatment.
After six weeks of Zetia treatment, LDL cholesterol decreased by an average of 12%, compared to a 3% drop in the placebo a group. The researchers also reported that 35% of patients receiving Zetia experienced an LDL decrease of at least 17%. Yet while these differences were statistically significant, the observed reductions are lackluster in light of higher LDL reductions seen in clinical tirals involving HIV-negative individuals. What's more, no significant changes in “good” HDL cholesterol or triglyceride levels were seen in either group.
Of the five patients who discontinued the study drug prematurely, two were receiving Zetia and three were receiving placebo at the time. One patient in the Zetia group discontinued due to low-level liver enzyme increases, whereas the other discontinued due to gastrointestinal discomfort. Among the three patients who discontinued placebo, a moderate increase in liver enzymes was reported in one patient, headache in another, and neuropathy in the third. Other side effects included headaches, diarrhea, and chest pain, although these side effects were rare and no more common among patients taking Zetia.
The study authors concluded that Zetia, used alone, led to significant declines in LDL cholesterol and was well tolerated. Not only do these data suggest that Zetia may be a useful option for patients with moderately elevated LDL cholesterol levels, they also suggest that the cholesterol blocker may be an important option for patients unable to take a statin.
For patients unable to reduce their LDL cholesterol levels using either Zetia or a statin alone, an 18-patient study conducted in Spain reported in the November 15 issue of AIDS suggested that Zetia, combined with the statin Pravachol (20 mg/day), is an option. However, even in this study, the average LDL cholesterol drop was only 15% after six months of treatment – a far less significant reduction than those observed in HIV-negative clinical trials.
Sources:
Wohl D, Hsue P, Richard S, et al. Ezetimibe’s effects on the LDL cholesterol levels of HIV-infected patients receiving HAART [Abstract 39]. 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, 2007.
Negredo E, Molto J, Puig J, et al. Ezetimibe, a promising lipid-lowering agent for the treatment of dyslipidaemia in HIV-infected patients with poor response to statins.AIDS 20(17):2159-64, 2006.
