Effects of First-Line Use of Nucleoside Analogues, Efavirenz, and Ritonavir-Boosted Protease Inhibitors on Lipid Levels

Abstract

Introduction: Treatment with ritonavir-boosted protease inhibitors or efavirenz and nucleoside analogues leads to rises in lipids, which might contribute to cardiovascular risk. Method: A MEDLINE search for clinical trials of first-line HAART with standardized 48-week lipids data available for combinations of two nucleoside analogues identified 13 with additional boosted protease inhibitor (PI/r) regimens (n = 5,281) and two with efavirenz (n = 1,087). Inverse-variance weighting was used to provide estimates of combined 48-week elevations in each lipid parameter. Results: The trials were well balanced for mean baseline total cholesterol (155 mg/dL), triglycerides (125 mg/dL), LDL (95 mg/dL), and HDL (37 mg/dL). The PIs showed two different types of lipid elevations: Group 1: saquinavir/r, atazanavir/r, and darunavir/r; and Group 2: lopinavir/ritonavir and fosamprenavir/r. There were greater elevations in total cholesterol and triglycerides for Group 2 compared to Group 1 but no differences in LDL or HDL between Group 1 and Group 2. Patients treated with efavirenz showed similar rises in total cholesterol and LDL compared with the PIs in Group 2 but showed smaller rises than in Group 1. In addition, patients treated with abacavir/lamivudine, zidovudine/lamiuvudine, or stavudine/lamivudine showed significantly higher elevations in all four lipid parameters, compared with patients given tenofovir/emtricitabine. Conclusion: There is a wide range of lipid elevations during 48 weeks of first-line HAART, which depends on the choice of antiretrovirals used.

Keywords:

• cholesterol
• HIV
• lipids
• meta-analysis
• nucleoside analogues
• protease inhibitors