Ezetimibe significantly lowers LDL cholesterol in patients taking HIV treatment, American researchers report in the October 15th edition of Clinical Infectious Diseases. The researchers found that mean LDL cholesterol levels were a “meaningful” 11% lower after six weeks of treatment with the drug.
HIV-positive patients may have an increased risk of heart disease, and it is possible that this is due in part to the increases in LDL cholesterol caused by some antiretroviral drugs.
Many patients treated with antiretrovirals are also taking statins to control their LDL cholesterol. However statins can interact with a number of anti-HIV drugs and also cause side-effects.
Ezetimibe can reduce cholesterol and it is often prescribed along with diet modification or statins to patients with high blood lipids. It is a potentially attractive drug for the treatment of elevated LDL cholesterol in HIV-positive patients because it is not processed by the body in the same way as antiretroviral drugs.
However, there is little information about the safety and effectiveness of ezetimibe treatment in patients with HIV.
Researchers in North Carolina and San Francisco therefore designed a study involving 48 patients taking HIV treatment. These patients were randomised to two arms.
For six weeks, patients in one arm of the study received daily treatment with 10mg of ezetimibe, whereas patients in the other arm received a placebo. This was followed by a two-week washout period. The patients then restarted treatment with the opposite therapy to that taken in their initial assignment. The patients were told to continue with their normal diet and not to modify their exercise habits.
All the patients were taking HIV treatment and all had fasting LDL cholesterol above 75mg/dl.
The patients mean LDL cholesterol on entry to the study was 128mg/dl. After six weeks of treatment, LDL cholesterol fell by a mean of 5.3% during treatment with ezetimibe, but increased by 5.5% during treatment with the placebo. This difference was significant (p = 0.04). Compared to patients taking the placebo, the mean cholesterol change attributable to ezetimibe therapy was 10.8% (p = 0.04).
Mean cholesterol fell by 4mg/dl during therapy with ezetimibe but increased by 4mg/dl during the placebo phase (p = 0.04).
As each 1% reduction in LDL cholesterol is thought to equal a 1% reduction in the risk of cardiovascular disease, the investigators believe that the reductions in LDL cholesterol seen during treatment with ezetimibe were “meaningful”, especially as increases in LDL cholesterol observed in patients taking antiretroviral therapy are usually in the region of 4% - 29%.
Therapy with ezetimibe did not affect levels of HDL (or good) cholesterol or levels of triglycerides.
Three patients discontinued treatment during treatment with ezetimibe, but three patients also discontinued treatment during the placebo or washout phase.
Good levels of adherence were reported.
“We found ezetimibe to be well tolerated in HIV-infected patients and to be capable of significant reductions in LDL cholesterol levels”, conclude the investigators. They add, “ezetimibe monotherapy should be considered to be a lipid-lowering option for HIV-infected patients requiring modest LDL-cholesterol reduction and may be particularly useful in patients who are unable to take or do not reach their treatment goals with statins.”
Wohl D. A. et al. Ezetimibe alone reduces low-density lipoprotein cholester0l in HIV-infected patients receiving combination antiretroviral therapy. Clin Infect Dis 47: 1105 – 1108, 2008.