Objective: Systematic review and meta-analysis of lipid outcomes for human immunodeficiency virus (HIV)-positive or HIV-infected patients treated with ezetimibe.
Methods: We conducted a literature search from 1946 to 2021 for trials studying the effectiveness of ezetimibe in hyperlipidaemic HIV patients. We included trials of all designs in which HIV patients on highly active antiretroviral therapy (HAART)/non-nucleoside reverse transcriptase inhibitor (NNRTI) therapy had hyperlipidaemia, were treated with ezetimibe, and reported lipid outcomes.
Results: Of thirteen eligible trials, five were randomized controlled trials (RCTs) and eight were single-arm trials. Two of the eligible RCTs were placebo-controlled; we performed a meta-analysis across those two trials for low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG). LDL-C was significantly lower in the ezetimibe arm (net change: -23.56 mg/dL, 95% CI: -40.22, -6.90 mg/dL). We then performed meta-analysis of the single-arm trials examining lipid outcomes after ezetimibe treatment which, like in the RCTs, revealed significant reductions of LDL-C (-23.89 mg/dL, 95% CI -29.94 to -17.83 mg/dL). In addition, significant reductions were seen for total cholesterol (TC) (-26.17 mg/dL, 95% CI -32.81 to -19.54 mg/dL) and TG (-18.57 mg/dL, 95% CI -34.01 to -3.14 mg/dL) but HDL-C did not show a change.
Conclusions: Evidence for LDL-C reduction is limited in RCTs; single-arm trial LDL-C reductions are consistent with the RCTs. In addition, significant reductions in TC and TG were also seen in the meta-analysis of the single arm trials. The single-arm trials' meta-analysis corroborates evidence from RCTs to suggest that ezetimibe can be an option for hyperlipidaemia among HIV patients with mildly elevated TC and LDL-C levels, especially in cases where statins are contra-indicated due to drug-drug interactions with concomitant anti-retroviral therapy.
Keywords: HAART; HIV; NNRTI; ezetimibe; hyperlipidaemia; systematic review and meta-analysis.