Distinct Lipidomic Profiles between People Living with HIV Treated with E/C/F/TAF or B/F/TAF: An Open-Label Prospective Cohort Study.

INTRODUCTION: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) has been increasingly replaced by bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in the treatment of human immunodeficiency virus (HIV) owing to its more favorable pharmacokinetics and fewer drug-drug interactions. However, the effect of this switch on plasma lipids and lipidomic profiles remains poorly characterized.

METHODS: HIV infected patients on an E/C/F/TAF regimen were recruited into the study and followed up every 12 weeks. Participants were divided into E/C/F/TAF and B/F/TAF groups depending on whether they were switched to B/F/TAF during follow-up. Clinical information and blood samples were collected at 0, 12, and 24 weeks, and lipidomic analysis was performed using liquid chromatography mass spectrometry.

RESULTS: No significant differences were observed between the groups at baseline. At week 24, patients switched to B/F/TAF had lower triglyceride [mmol/L; 1.23 (0.62) versus 2.03 (0.75), P = 0.001] and very low-density lipoprotein cholesterol [mmol/L; 0.64 (0.26) versus 0.84 (0.32), P = 0.037) compared with patients who continued E/C/F/TAF therapy. Small decrease from baseline in Framingham general cardiovascular risk score (FRS) was observed in the B/F/TAF arm [week (W) 0: 2.59 (1.57) versus W24: 2.18 (1.01), P = 0.043]. Lipidomic analysis indicated that E/C/F/TAF treatment increased the levels of several diglycerides (DGs), triacylglycerols (TAGs), and lyso-phosphatidylcholines (LPCs), whereas switching to B/F/TAF led to increased sphingolipids and glycerophospholipids. After adjusting for demographic and clinical parameters, only DG (16:0/18:2), DG (18:2/22:6), DG (18:3/18:2), DG (20:5/18:2), TAG (18:3/18:2/21:5), TAG (20:5/18:2/22:6), and LPC (22:6) were found to be significantly associated with FRS (regression coefficient of 0.17-6.02, P < 0.05). Most of these FRS associate lipid species were significantly elevated in individuals treated with E/C/F/TAF instead of individuals treated with B/F/TAF.

CONCLUSION: E/C/F/TAF promotes the accumulation of lipid species closely associated with cardiovascular disease (CVD) risk among people living with HIV, whereas B/F/TAF has a decreased impact on CVD-related lipid profile and is associated with lower CVD risk. A graphical abstract is available with this article.

TRIAL REGISTRATION: ClinicalTrials.gov; identifier, NCT06019273.