Despite having a better renal and bone safety profile, tenofovir alafenamide (TAF) is associated with greater increases in cholesterol levels when compared to tenofovir disoproxil fumarate (TDF). Because hyperlipidemia is a major risk factor for cardiovascular disease (CVD), assessing for and reducing risk in adults with HIV is an important part of medical care. This study evaluated the impact of lipid changes on predicted atherosclerotic cardiovascular disease (ASCVD) risk. Participants included 1,733 ARV-naïve adult patients from two clinical trials (GS-US-292-0104 and GS-US-292-0111) randomized to initiate TAF or TDF co-formulated with elvitegravir/cobicistat/emtricitabine. At week -96 of the study, the estimated 10-year ASCVD risk was calculated by using the 2013 American College of Cardiology/AHA Pooled Cohort Risk Equations. Changes in the 10-year risk from greater than 7.5% for patients on TAF versus TDF were used to assess eligibility for statin therapy based on current national guidelines. Participants initiating TDF or TAF the study showed small but significant increases in median fasting lipid parameters including total cholesterol that was 163 mg/dL to 177 mg/dL for TDF vs 160 mg/dL to 191 mg/dL for TAF. For LDL these numbers were 101 mg/dL to 119 mg/dL vs 104 mg/dL to 112 mg/dL and for HDL mg/dL 44 to 51 mg/dL vs 44 to 48 mg/dL. At baseline, 18% and 23% on TAF versus TDF had a 10-year ASCVD risk score ≥7.5%. However, the mean baseline risk scores were low overall for TAF (4.9%) versus TDF (5.4%). At week-96 the risk score was 6.1% for TAF vs 6.2% for TDF. The changes in ASCVD risk from baseline were due to increasing age along with larger LDL increase with TAF and smaller HDL increases with TDF. Eligibility for high-intensity statin therapy were similar for TAF versus TDF groups (19% vs 21%). The author’s general conclusion is that although lipid changes occurred with TAF as part of co-formulated regimens, the changes do not substantively affect CVD risk profiles compared with TDF.

Author’s Commentary:

This is reassuring data as the majority of patients these days are taking TAF and not TDF containing regimens, especially as part of single-tablet regimens and as PrEP in some cases. Hopefully, we are not trading off a decrease in renal and bone toxicity for an increase in CVD with TAF. This study suggests that is not the case. Despite elevations in LDL with TAF, the overall risk does not appear to increase. Worth noting, is that overall 20% of the subjects in this trial were statin eligible based on CVD risk but at 96 weeks, only 4% were receiving statin therapy.