Atherosclerotic Cardiovascular Disease Risk Profile of Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate

Abstract

Background In human immunodeficiency virus (HIV) treatment, tenofovir alafenamide (TAF) is associated with greater increases in all fasting cholesterol subgroups compared with tenofovir disoproxil fumarate (TDF). Because lipid abnormalities may contribute to cardiovascular morbidity and mortality, cardiovascular risk assessment is integral to routine HIV care. This post hoc study evaluates the impact of lipid changes on predicted atherosclerotic cardiovascular disease (ASCVD) risk and statin eligibility in treatment-naive adults living with HIV treated with TAF or TDF. Methods Participants (N = 1744) were randomized (1:1) to initiate TAF or TDF, each coformulated with elvitegravir/cobicistat/emtricitabine (studies GS-US-292-0104 and GS-US-292-0111). Eligibility for statin therapy and estimated 10-year ASCVD risk among adults aged 40–79 years treated with TAF or TDF for 96 weeks (W96) were analyzed based on American College of Cardiology/American Heart Association Pooled Cohort Equations. Categorical shifts in 10-year ASCVD risk from <7.5% to ≥7.5% by W96 on TAF versus TDF were calculated. Results Participants initiating TAF versus TDF in the overall study population showed small but significant increases in median fasting lipid parameters at W96, including total cholesterol (191 vs 177 mg/dL; P < .001), low-density lipoprotein ([LDL] 119 vs 112 mg/dL; P < .001), and high-density lipoprotein ([HDL] 51 vs 48 mg/dL; P < .001), respectively. At baseline, 18% and 23% on TAF versus TDF had a 10-year ASCVD risk score ≥7.5%, with mean risk scores low overall for TAF versus TDF at baseline (4.9% vs 5.4%; P = .35) and W96 (6.1% vs 6.2%; P = .04). Increases in ASCVD risk from baseline to W96 were driven by both increasing age and changes in total cholesterol (TC) and HDL cholesterol. At W96, TC/HDL ratios (median) were 3.7 for both groups (P = .69). There was no difference between shifts in categorical risk for TAF versus TDF (9% vs 5%; P = .19). Eligibility for high-intensity statin therapy were similar for TAF versus TDF groups (19% vs 21%; P = .47). Conclusions Lipid changes with TAF as part of coformulated regimens do not substantively affect CVD risk profiles compared with TDF.

A Review and Clinical Understanding of Tenofovir: Tenofovir Disoproxil Fumarate versus Tenofovir Alafenamide

“…36 In one randomized study of TAF versus TDF, cardiovascular safety end points were monitored for 96 weeks, including fasting lipids, proportion eligible for statin therapy, cardiovascular adverse events, and estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk. 37 No significant differences between groups were noted, except for the mean estimated 10-year ASCVD risk comparing TAF versus TDF (6.1% versus 6.2%; P = .04).…”

Efficacy and safety of co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in HIV-positive patients: real-world data

“…41 A post hoc study evaluated the impact of lipid changes on predicted atherosclerotic cardiovascular disease (ASCVD) risk and statin eligibility in treatment-naïve 1774 adults living with HIV treated with TAF or TDF. 42 In that study, lipid changes (increases in total cholesterol, LDL and HDL) with TAF as part of co-formulated regimens did not substantively affect CVD risk profiles compared to TDF. However, considering the increasing age and other cardiovascular risk factors of patients living with HIV, changes in lipid parameters should be followed up closely and for the long term.…”

Changing Trends in Lipid Profile and Biomarkers of Renal Function and Bone Metabolism Before and After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide: a Prospective Observational Study

“…The elevation of biomarkers of lipids such as LDL-C was observed to have signi cance. Previous studies have also shown the elevation in the LDL-C and TG levels, but the range of elevation depended on the observational period, and the characteristics of the participants (17)(18)(19). One of the major risks for hyperlipidemia that was identi ed after switching to TAF was the elevation at beginning in TG or LDL-C levels (20) although opposite results also reported (21).…”