Short-term ezetimibe is well tolerated and effective in combination with statin therapy to treat elevated LDL cholesterol in HIV-infected patients.

TitleShort-term ezetimibe is well tolerated and effective in combination with statin therapy to treat elevated LDL cholesterol in HIV-infected patients.
Publication TypeJournal Article
Year of Publication2009
AuthorsChow D, Chen H, Glesby MJ, Busti A, Souza S, Andersen J, Kohrs S, Wu J, Koletar SL
JournalAIDS
Volume23
Issue16
Pagination2133-41
Date Published2009 Oct 23
ISSN1473-5571
KeywordsAnticholesteremic Agents, Antiretroviral Therapy, Highly Active, Azetidines, CD4 Lymphocyte Count, Cholesterol, LDL, Cross-Over Studies, Double-Blind Method, Drug Administration Schedule, Drug Therapy, Combination, Ezetimibe, Female, HIV Infections, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Male, Middle Aged
Abstract

BACKGROUND: Ezetimibe inhibits intestinal absorption of cholesterol.

METHODS: Multicentered double-blind, randomized, placebo-controlled, crossover study to determine the short-term safety, efficacy, and tolerability of ezetimibe in combination with ongoing statin therapy in HIV-infected adults with elevated low-density lipoprotein cholesterol (LDL-C). Participants on stable HAART with fasting LDL-C at least 130 mg/dl and stable statin were randomized to ezetimibe 10 mg daily or placebo for 12 weeks followed by 4 weeks of washout and then 12 weeks with alternative study assignment. Percentage and absolute change in LDL-C (primary endpoint), total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), apolipoprotein B, and high sensitivity C-reactive protein were compared. Changes in clinical symptoms and safety laboratory measurements were assessed.

RESULTS: Forty-four participants enrolled: 70% men, median age 49 years, 43% White/Non-Hispanic, median CD4 cell count 547 cells/microl, and 95% HIV RNA less than 50 copies/ml. Median (interquartile range) percentage change in LDL-C was -20.8% (-25.4, -10.7) with ezetimibe and -0.7% (-10.3,18.6) with placebo; the median within-participant effect of ezetimibe was -14.1% (-33.0, -5.0; P < 0.0001). Median difference in absolute LDL-C values between ezetimibe and placebo was -32 mg/dl (-58, -6, P < 0.0001). Significant differences in within-participant effect of ezetimibe were noted for total cholesterol -18.60% (-27.22, -11.67, P < 0.001), non-HDL-C -23.18% (-33.14, -14.36, P < 0.0001), and apolipoprotein B -8.73% (-18.75, 1.99, P = 0.02). No significant changes seen in HDL-C, triglyceride, or high sensitivity C-reactive protein. Ezetimibe was well tolerated. Adverse events were similar between phases.

CONCLUSION: The present short-term study found adding ezetimibe to ongoing statin therapy was well tolerated and effective in reducing LDL-C, total cholesterol, non-HDL-C, and apolipoprotein B. Adding ezetimibe to statin therapy offers reasonable treatment option for HIV-infected patients with elevated LDL-C.

DOI10.1097/QAD.0b013e32833068e3
Alternate JournalAIDS
PubMed ID19770624
PubMed Central IDPMC2782438
Grant ListAI68634 / AI / NIAID NIH HHS / United States
AI68636 / AI / NIAID NIH HHS / United States
K23 HL088981 / HL / NHLBI NIH HHS / United States
K23 HL088981-02 / HL / NHLBI NIH HHS / United States
U01 AI069474 / AI / NIAID NIH HHS / United States
U01 AI069474-02 / AI / NIAID NIH HHS / United States