title: Tenofovir alafenamide vs. tenofovir disoproxil fumarate in single tablet regimens 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 a single-tablet regimen (STR) for the initial treatment of HIV-1 infection.
  
  
  METHODS
  Phase 2, randomized, double-blind, double-dummy, multicenter, active-controlled study.
  
  
  METHODS
  Antiretroviral naive adults with HIV-1 RNA ≥5000 copies per milliliter and a CD4 count ≥50 cells per microliter were randomized 2:1 to receive an STR of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF), plus placebo for 48 weeks.
  
  
  RESULTS
  Patients on both E/C/F/TAF (n = 112) and E/C/F/TDF (n = 58) had high rates of virologic suppression (<50 HIV copies per milliliter) at week 24 (86.6%; 89.7%) and at week 48 (88.4%; 87.9%), and had similar improvements in CD4 at week 48 (177; 204), respectively. Both treatments were well tolerated, and most adverse events were self-limiting and of mild to moderate severity. Compared with patients on E/C/F/TDF, patients on E/C/F/TAF had smaller reductions in estimated creatinine clearance (-5.5 vs. -10.1 mL/min, P = 0.041), significantly less renal tubular proteinuria, and smaller changes in bone mineral density for hip (-0.62% vs. -2.39%, P < 0.001) and spine (-1.00% vs. -3.37%, P < 0.001). Patients on E/C/F/TAF had higher increases in total cholesterol, low-density lipoprotein, and high-density lipoprotein, but the total cholesterol/high-density lipoprotein ratio was unchanged for both.
  
  
  CONCLUSIONS
  Treatment-naive patients given the STR that contained either TAF or TDF achieved a high rate of virologic success. Compared with those receiving TDF, patients on E/C/F/TAF experienced significantly smaller changes in estimated creatinine clearance, renal tubular proteinuria, and bone mineral density.
authors.affiliation: *Division of Infectious Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; †Division of Infectious Diseases, Stanford University, Atherton, CA; ‡Infectious Diseases Division, Henry Ford Hospital, Detroit, Detroit, MI; §Department of Internal Medicine, George Washington University Hospital, Washington, DC; ‖Orlando Immunology Center, Orlando, FL; ¶Centre for Global Health, Kings College London, Weston Education Centre, London, United Kingdom; and #Gilead Sciences, Foster City, CA.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Sax
authors.forename: Andrew
authors.initials: A
authors.lastname: Zolopa
authors.forename: Indira
authors.initials: I
authors.lastname: Brar
authors.forename: Richard
authors.initials: R
authors.lastname: Elion
authors.forename: Roberto
authors.initials: R
authors.lastname: Ortiz
authors.forename: Frank
authors.initials: F
authors.lastname: Post
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Christian
authors.initials: C
authors.lastname: Callebaut
authors.forename: Hal
authors.initials: H
authors.lastname: Martin
authors.forename: Marshall W
authors.initials: MW
authors.lastname: Fordyce
authors.forename: Scott
authors.initials: S
authors.lastname: McCallister
mesh_terms: D015502:Absorptiometry, Photon; D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000284:Administration, Oral; D000328:Adult; D000409:Alanine; D015519:Bone Density; D018791:CD4 Lymphocyte Count; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000652:urine; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D011355:Prodrugs / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011507:Proteinuria; D012367:RNA, Viral / Q000097:blood; D000068698:Tenofovir / Q000031:analogs & derivatives; D014481:United States
chemical_list: D011355:Prodrugs; D012367:RNA, Viral; D002784:Cholesterol; D000068698:Tenofovir; D003404:Creatinine; C442442:tenofovir alafenamide; D000225:Adenine; D000409:Alanine