The Lipid-Lowering Effect of Tenofovir/Emtricitabine: A Randomized, Crossover, Double-Blind, Placebo-Controlled Trial

© 2015 The Author 2015. Background. It is unknown if tenofovir disoproxil fumarate (TDF), which is often coformulated with the lipid-neutral emtricitabine (FTC), has a lipid-lowering effect. Methods. We performed a randomized, crossover, double-blind, placebo-controlled clinical trial on human immunodeficiency virus type 1 (HIV-1)-infected subjects with HIV-1 RNA < 50 copies/mL during 6 months on stable darunavir/ritonavir (800/100 mg once daily) or lopinavir/ritonavir (400/100 mg twice daily) monotherapy, fasting total cholesterol (TC) 200 mg/dL or low-density lipoprotein cholesterol (LDL-c) 130 mg/dL, and no lipid-lowering drugs. In arm 1, TDF/FTC was added for 12 weeks, followed by 12 weeks of placebo (washout) and 12 additional weeks of placebo (placebo period). Subjects in arm 2 added placebo for 12 weeks (placebo period) followed by TDF/FTC for 12 weeks and placebo for 12 additional weeks (washout). The primary endpoint was change in median fasting TC levels. Results. Of 46 subjects enrolled, 56% received darunavir/ritonavir and 44% lopinavir/ritonavir. Exposure to TDF/FTC reduced TC from 234 to 205 mg/dL (P <. 001), LDL-c from 155 to 128 mg/dL (P <. 001), and high-density lipoprotein cholesterol (HDL-c) from 50.3 to 44.5 mg/dL (P <. 001). It also decreased the proportion of subjects with fasting TC ?200 mg/dL from 86.7% to 56.8% (P =. 001), and LDL-c ?130 mg/dL from 87.8% to 43.9% (P <. 001). After 12 weeks, TDF/FTC exposure was associated with lower TC and LDL-c levels than placebo (P =. 001 and P =. 002, respectively). The TC/HDL-c ratio and triglyceride levels did not change with TDF/FTC exposure. Conclusions. Coformulated TDF/FTC has an intrinsic lipid-lowering effect, likely attributable to TDF.