JAC Advance Access published online on October 23, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkn440
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Research letter |
Use of ezetimibe during HIV infection
Imperial College School of Medicine, The St Stephen's Centre, The Chelsea and Westminster Hospital, London SW10 9NH, UK
* Corresponding author. E-mail: j.stebbing{at}imperial.ac.uk
Key Words: ezetimibe , HIV , cholesterol , study
There has been substantial recent controversy regarding the use of ezetimibe, a cholesterol-lowering agent that blocks intestinal absorption of cholesterol. The results of the ENHANCE trial failed to show a benefit of adding ezetimibe to statin therapy.1,2 Specifically, in patients with familial hypercholesterolaemia, combined therapy with ezetimibe and simvastatin did not result in a significant difference in changes in intima–media thickness, when compared with simvastatin alone, despite decreases in levels of low-density lipoprotein (LDL)-cholesterol and C-reactive protein in the ezetimibe arm. An accompanying editorial in the New England Journal of Medicine concluded that ‘niacin, fibrates, and resins should be considered when diet, exercise, and a statin have failed to achieve the target, with ezetimibe reserved for patients who cannot tolerate these agents’.3 Subsequent data have similarly failed to show a benefit of ezetimibe and simvastatin over placebo in the SEAS trial, which examined cardiac endpoints in individuals with aortic stenosis.4,5 The metabolic complications of HIV and its treatment are well known, and data from small uncontrolled studies have shown that ezetimibe effectively decreases LDL-cholesterol in HIV-infected patients,6 including those with a poor response to statins7 and those receiving protease inhibitors (PIs).8
To investigate this further, we examined the effects of ezetimibe in 29 HIV-infected individuals either alone or in patients receiving statins. Of these individuals, 16 were receiving PI-based highly active antiretroviral therapy (HAART) and 11 were receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART with no significant differences in baseline total cholesterol or triglycerides between these groups. A total of 17 patients studied received ezetimibe concurrently with statins. Over 12 weeks, we observed a significant 18.0% reduction in serum total cholesterol (Wilcoxon signed-rank P < 0.01) and a 28.9% decrease in serum triglycerides (Wilcoxon signed-rank P < 0.05) regardless of whether patients received statins or not, or the type of antiretroviral therapy as analysed by the Mann–Whitney U-test (Table 1). A total of eight patients (40%, McNemar's P < 0.02) had a normalized serum total cholesterol (<5 mmol/L), at the end of the follow-up period. The proportion of patients with normalized serum triglycerides (<2 mmol/L) was not significant. There were no significant differences in reduction of either serum total cholesterol or triglycerides in those receiving ezetimibe alone (n = 12) or in those receiving it with statins (n = 17). One individual stopped as she was attempting to conceive, another due to nausea and anorexia.
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Limitations of this work include the small sample size, lack of measurement of LDL levels, length of time patients were exposed to HAART and level of viraemia (which is an independent cause of dyslipidaemia in HIV). However, these data suggest that in patients such as those infected with HIV-1, who are on concomitant medications with effects on the cytochrome P450 system (unlike ezetimibe), we still recommend the use of ezetimibe. This may be either as monotherapy in the second-line treatment of HAART-induced dyslipidaemia, if hypercholesterolaemia is refractory to statins, or if the patient does not tolerate statins. Although the results of the SEAS and ENHANCE trials have diminished confidence in ezetimibe, a larger prospective study in HIV-positive individuals should be undertaken, including intima–media thickness measurements and, if possible, cardiovascular outcomes.
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None.
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None to declare.
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1 . Kastelein JJ, Akdim F, Stroes ES, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med (2008) 358:1431–43.
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Brown BG, Taylor AJ. Does ENHANCE diminish confidence in lowering LDL or in ezetimibe? N Engl J Med (2008) 358:1504–7.
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Drazen JM, Jarcho JA, Morrissey S, et al. Cholesterol lowering and ezetimibe. N Engl J Med (2008) 358:1507–8.
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Rossebo AB, Pedersen TR, Boman K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med (2008) 359:1343–56.
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Peto R, Emberson J, Landray M, et al. Analyses of cancer data from three ezetimibe trials. N Engl J Med (2008) 359:1357–66.
6 . Coll B, Aragones G, Parra S, et al. Ezetimibe effectively decreases LDL-cholesterol in HIV-infected patients. AIDS (2006) 20:1675–7.[Web of Science][Medline]
7 . 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 (2006) 20:2159–64.[Web of Science][Medline]
8 . Berg-Wolf MV, Klibanov OM, Gaughan JP, et al. Ezetimibe combined with low-dose statin effectively lowers LDL in protease inhibitor treated patients. AIDS Patient Care STDS (2008) 22:483–8.[Medline]
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