Tenofovir alafenamide vs. tenofovir disoproxil fumarate in single tablet regimens for initial HIV-1 therapy: a randomized phase 2 study

J Acquir Immune Defic Syndr. 2014 Sep 1;67(1):52-8. doi: 10.1097/QAI.0000000000000225.

Abstract

Objectives: 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.

Design: 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.

Trial registration: ClinicalTrials.gov NCT00118898.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Adenine / administration & dosage
  • Adenine / analogs & derivatives*
  • Adenine / pharmacokinetics
  • Administration, Oral
  • Adult
  • Bone Density
  • CD4 Lymphocyte Count
  • Cholesterol / blood
  • Creatinine / urine
  • Double-Blind Method
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / metabolism
  • HIV Infections / virology
  • HIV-1 / isolation & purification*
  • Humans
  • Male
  • Prodrugs / administration & dosage*
  • Prodrugs / pharmacokinetics
  • Proteinuria
  • RNA, Viral / blood
  • United States

Substances

  • Prodrugs
  • RNA, Viral
  • Cholesterol
  • Creatinine
  • GS-7340
  • Adenine

Associated data

  • ClinicalTrials.gov/NCT00118898