title: The lipid-lowering effect of tenofovir/emtricitabine: a randomized, crossover, double-blind, placebo-controlled trial.
abstract: 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.
  
  
  BACKGROUND
  NCT01458977.
authors: Lluita contra la SIDA Foundation, Germans Trias i Pujol University Hospital Universitat Autònoma de Barcelona.
authors: José R
authors: JR
authors: Santos
authors: HIV Unit, Infectious Diseases Service, Bellvitge University Hospital, Bellvitge Biomedical Research Institute, Hospitalet de Llobregat.
authors: María
authors: M
authors: Saumoy
authors: Universitat Autònoma de Barcelona Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Barcelona.
authors: Adrian
authors: A
authors: Curran
authors: Lluita contra la SIDA Foundation, Germans Trias i Pujol University Hospital.
authors: Isabel
authors: I
authors: Bravo
authors: Lluita contra la SIDA Foundation, Germans Trias i Pujol University Hospital Universitat Autònoma de Barcelona.
authors: Josep M
authors: JM
authors: Llibre
authors: Universitat Autònoma de Barcelona Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Barcelona.
authors: Jordi
authors: J
authors: Navarro
authors: Lluita contra la SIDA Foundation, Germans Trias i Pujol University Hospital.
authors: Carla
authors: C
authors: Estany
authors: HIV Unit, Infectious Diseases Service, Bellvitge University Hospital, Bellvitge Biomedical Research Institute, Hospitalet de Llobregat.
authors: Daniel
authors: D
authors: Podzamczer
authors: Universitat Autònoma de Barcelona Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Barcelona.
authors: Esteban
authors: E
authors: Ribera
authors: Lluita contra la SIDA Foundation, Germans Trias i Pujol University Hospital Universitat de Vic-Universitat Central de Catalunya, Vic.
authors: Eugènia
authors: E
authors: Negredo
authors: Lluita contra la SIDA Foundation, Germans Trias i Pujol University Hospital Universitat Autònoma de Barcelona Universitat de Vic-Universitat Central de Catalunya, Vic IrsiCaixa AIDS Research Institute, Barcelona, Spain.
authors: Bonaventura
authors: B
authors: Clotet
authors: Lluita contra la SIDA Foundation, Germans Trias i Pujol University Hospital Universitat Autònoma de Barcelona Universitat de Vic-Universitat Central de Catalunya, Vic IrsiCaixa AIDS Research Institute, Barcelona, Spain.
authors: Roger
authors: R
authors: Paredes
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D018592:Cross-Over Studies; D004311:Double-Blind Method; D000068679:Emtricitabine / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D000068698:Tenofovir / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D008055:Lipids; D010919:Placebos; D000068698:Tenofovir; D000068679:Emtricitabine
keywords: LDL cholesterol; boosted protease inhibitor monotherapy; coformulated tenofovir/emtricitabine; lipid-lowering effect; total cholesterol