Following our analysis we conclude that adding ezetimibe improves the lipid profile in patients with HIV on maximally tolerated doses of lipid lowering therapy.
In our group of 33 patients we found significant reductions in serum concentrations of total cholesterol, triglycerides, LDL and apolipoprotein B100 following the addition of ezetimibe. Serum concentrations of HDL also rose significantly following this intervention. These gains were achieved without any adverse events.
Our findings are concordant with studies which have assessed the efficacy of ezetimibe in non-HIV populations [5
]. As one of the proposed mechanisms of dyslipidemia in patients with HIV is due to ARV therapy[9
], we felt it was necessary to demonstrate the efficacy of ezetimibe in this group.
Only two studies have described the use of ezetimibe in patients with HIV. Coll et al compared ezetimibe monotherapy to fluvastatin monotherapy in 20 HIV positive patients. Serum concentrations of LDL were reduced by 20% with ezetimibe monotherapy [7
]. As our practice is to add ezetimibe to other lipid lowering therapy, only 3 patients in our study were on ezetimibe monotherapy. The serum LDL concentration was reduced by 32% in this subgroup. This result was not statistically significant owing to the small number of patients in this subgroup.
Negredo et al. added ezetimibe in 19 patients with HIV who were not at target while on pravastatin. After 24 weeks of combination therapy of ezetimibe and pravastatin, 61.5% of patients achieved an LDL less than 3.36 mmol/L (130 mg/dl). At baseline there were 14 patients in our study on statin therapy who had a serum LDL concentration greater than 3.36 mmol/L. 9 of these patients (64%) achieved an LDL of less than 3.36 mmol/L following the addition of ezetimibe.
In our center, in the absence of consensus guidelines for the treatment of dyslipidemia in patients with HIV, we currently treat HIV positive patients to at least moderate risk lipid profile targets (total cholesterol concentration of less than or equal to 5.0 mmol/L, an LDL concentration of less than or equal to 3.5 mmol/L and serum total cholesterol to HDL ratio of less than or equal to 5.0). Prior to ezetimibe therapy, none of the patients met all targets despite maximally tolerated lipid lowering therapy (none of the patients met the total cholesterol target, 6 of 25 patients met the LDL target and 4 of 33 patients met the total cholesterol to HDL ratio target). Following the addition of ezetimibe the total cholesterol was reduced to less than or equal to 5.0 mmol/L 13 of 33 patients (39%). The LDL concentration was reduced to less than or equal to 3.5 mmol/L in 15 of 25 patients (60%). The ratio of total cholesterol to HDL ratio was reduced to less than or equal to 5.0 in 15 of 33 patients (45%). The results were then analyzed according to baseline lipid lowering therapy. Figure describes which patients met moderate risk lipid targets following the addition of ezetimibe despite not meeting them at baseline.
Ezetimibe add-on therapy: Percent of patients reaching targets for moderate risk according to baseline lipid agent.
The current published guidelines recommend diet and exercise counseling, considering altering the ARV regimen or adding lipid lowering medications for dyslipidemia in patients on ARV therapy [3
]. A statin is suggested for LDL elevations and a fibrate is suggested for serum triglycerides elevations. The current guidelines do not yet recommend the use of ezetimibe therapy in this group.
Our study is the first to analyze the efficacy of adding ezetimibe to maximally tolerated doses of the lipid lowering therapy including highly potent statins, fibrates and combinations of a statin and a fibrate. Significant improvements in the lipid profile following the addition of ezetimibe were seen. Furthermore, there were no adverse events. We conclude that if the lipid targets are not met after maximally tolerated doses of lipid lowering therapy with a statin and/or fibrate, ezetimibe is safe and effective.