Adding ezetimibe (Zetia) to pravastatin can safely and effectively reduce lipids in HIV-positive patients with metabolic complications caused by antiretrovirals, according to a Spanish study presented to the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy in Washington DC last month.
Ezetimibe is the first selective inhibitor of cholesterol. It is absorbed in the duodenum and has been shown to improve the efficacy of the lipid-lowering drugs statins.
Elevated cholesterol and triglycerides are commonly seen in patients taking antiretroviral therapy. Lipid-lowering drugs need to be used with caution as, in common with many anti-HIV agents, they use the CYP3A4 cytochrome to be metabolised increasing the risk of serious side-effects.
Studies suggest that lipid-lowering drugs are only partially effective at correcting metabolic abnormalities when they have been used in HIV-positive patients.
Investigators wished to see if adding a 10mg daily dose of ezetimibe to pravastatin could safely and effectively reduce cholesterol and triglycerides in HIV-positive patients who were taking anti-HIV therapy with persistently elevated cholesterol despite pravastatin therapy.
The study involved 18 individuals, 61% of whom were men. Nine were taking a protease inhibitor and nine were taking the non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine as part of a stable anti-HIV treatment regimen. All had been taking a 20mg daily dose of pravastatin for at least six months yet still had LDL cholesterol above 130mg/dl.
At baseline, mean total cholesterol was 237mg/dl, mean LDL cholesterol was 149mg/dl, and mean triglycerides were 179mg/dl.
Six weeks after adding ezetimibe mean total cholesterol fell to 201mg/dl, mean LDL cholesterol to 120mg/dl and mean triglycerides to 133mg/dl. Mean HDL cholesterol remained stable.
The investigators noted that six weeks after adding ezetimibe to lipid-lowering therapy, normal total cholesterol was achieved in 53% of patients and normal LDL cholesterol in 64%.
No significant changes in the pharmacokinetics of antiretrovirals were seen, however trough levels of nevirapine fell by an average of 17% and trough levels of protease inhibitors increased by 10%.
No serious adverse events were seen, although two patients developed constipation.
The investigators conclude that according to their data, in the short term at least, “the addition of ezetimibe to low dose pravastatin significantly improved lipid parameters in patients with hypercholesterolemia who had responded poorly to pravastatin alone.” They add, “the lack of an interaction with cytochrome CYP3A4 and its good tolerance mean that ezetimibe can be given jointly with antiretrovirals without the risk of pharmacokinetic interactions or greater toxicity.”
Negredo E et al. Ezetimibe, a selective inhibitor of cholesterol absorption, as a new strategy for treatment of hypercholesterolemia secondary to antiretroviral therapy. 45th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington DC, abstract H-336, 2005.