Journal Article

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

Bravo, Isabel, Curran, Adrian, Paredes, Roger, Llibre, Josep M., Saumoy, María, Podzamczer, Daniel, Navarro, Jordi, Santos, José R., Estany, Carla, Ribera, Esteban, Negredo, Eugènia, Clotet, Bonaventura

2015

Overview

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. Clinical Trials Registration. NCT01458977.

• Publisher: Oxford University Press
• Subject: Adult / Anti-HIV Agents - pharmacology / Anti-HIV Agents - therapeutic use / Antiretroviral drugs / ARTICLES AND COMMENTARIES / Cholesterol / Clinical trials / Cross-Over Studies / Double-Blind Method / Emtricitabine - pharmacology / Emtricitabine - therapeutic use / Female / HIV / HIV Infections - drug therapy / HIV Infections - epidemiology / HIV Infections - physiopathology / Human immunodeficiency virus / Humans / Lipids / Lipids - blood / Low density lipoprotein / Male / Middle Aged / Placebos / Ritonavir / Tenofovir - pharmacology / Tenofovir - therapeutic use / Triglycerides