title: Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate in the First Protease Inhibitor-Based Single-Tablet Regimen for Initial HIV-1 Therapy: A Randomized Phase 2 Study.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of the novel tenofovir prodrug, tenofovir alafenamide (TAF), as part of the first protease inhibitor-based single-tablet regimen (STR) for initial treatment of HIV-1 infection.
  
  
  METHODS
  Antiretroviral therapy (ART)-naive adults with estimated glomerular filtration rate ≥ 70 mL/min were randomized 2:1 to receive the darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) STR (TAF: N = 103) or darunavir + cobicistat + emtricitabine/tenofovir disoproxil fumarate (TDF: N = 50) once daily with matched placebos for 48 weeks.
  
  
  RESULTS
  At week 24, viral suppression (HIV-1 RNA <50 copies/mL) rates were similar (TAF 74.8% vs. TDF 74.0%). At week 48, rates were TAF 76.7% vs. TDF 84.0%; the difference was driven by higher rate of discontinuations in TAF (6.8%) vs. TDF (2%). Among those with virologic failure, none developed resistance. Most adverse events were of mild/moderate severity. The mean change in serum creatinine from baseline at week 48 was 0.06 mg/dL (95% confidence interval: 0.04 to 0.08) for TAF vs. 0.09 mg/dL (95% confidence interval: 0.05 to 0.14) for TDF (P = 0.053). The % change in retinol binding protein/Cr ratio was +9 (TAF) vs. +54 (TDF), P = 0.003; the % change in urine β-2 microglobulin/Cr ratio was -42.0 (TAF) vs. +2.3 (TDF), P = 0.002. The % change in hip bone mineral density (BMD) was -0.84 (TAF) vs. -3.82 (TDF), P < 0.001 and in spine BMD was -1.57 (TAF) vs. -3.62 (TDF), P = 0.003. There were no fractures in either group.
  
  
  CONCLUSIONS
  The TAF arm had significantly improved renal and bone safety parameters: less proteinuria and less change in hip and spine BMD, consistent with results from a similarly designed study of the elvitegravir/C/F/TAF STR. This D/C/F/TAF STR offers a promising option for initial HIV treatment, with the high barrier to resistance of darunavir, and the potential for improved long-term renal and bone safety with TAF.
authors: *Gordon Crofoot Research, Southern California Men's Medical Group/Men's Health Foundation, Assistant Professor of Clinical Medicine, Univeristy of California, Los Angeles, Los Angeles, CA; †Houston, TX; ‡Tarrant County Infectious Disease Associates, Fort Worth, TX; §Clinical Associate Professor in the Division of Allergy and Infectious Diseases, University of Washington School of Medicine, Seattle, WA; ‖Kaiser Permanente, Sacramento, CA; ¶Therapeutic Concepts, Houston, TX; #DCOL Center for Clinical Research, Longview, TX; **La Playa Medical Group and Clinical Research, San Diego, CA; ††Center for AIDS Research, The University of Alabama at Birmingham, Birmingham, AL; and ‡‡Gilead Sciences, Foster City, CA.
authors: Anthony
authors: A
authors: Mills
authors: Gordon
authors: G
authors: Crofoot
authors: Cheryl
authors: C
authors: McDonald
authors: Peter
authors: P
authors: Shalit
authors: Jason A
authors: JA
authors: Flamm
authors: Joseph
authors: J
authors: Gathe
authors: Anita
authors: A
authors: Scribner
authors: David
authors: D
authors: Shamblaw
authors: Michael
authors: M
authors: Saag
authors: Huyen
authors: H
authors: Cao
authors: Hal
authors: H
authors: Martin
authors: Moupali
authors: M
authors: Das
authors: Anne
authors: A
authors: Thomas
authors: Hui C
authors: HC
authors: Liu
authors: Mingjin
authors: M
authors: Yan
authors: Christian
authors: C
authors: Callebaut
authors: Joseph
authors: J
authors: Custodio
authors: Andrew
authors: A
authors: Cheng
authors: Scott
authors: S
authors: McCallister
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000409:Alanine; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D000068698:Tenofovir / Q000031:analogs & derivatives
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D012367:RNA, Viral; D000068698:Tenofovir; C442442:tenofovir alafenamide; D000225:Adenine; D000409:Alanine