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

AbstractOBJECTIVES:
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.
AuthorsPaul E Sax, Andrew Zolopa, Indira Brar, Richard Elion, Roberto Ortiz, Frank Post, Hui Wang, Christian Callebaut, Hal Martin, Marshall W Fordyce, Scott McCallister
JournalJournal of acquired immune deficiency syndromes (1999) (J Acquir Immune Defic Syndr) Vol. 67 Issue 1 Pg. 52-8 (Sep 01 2014) ISSN: 1944-7884 [Electronic] United States
PMID24872136 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Prodrugs
  • RNA, Viral
  • Cholesterol
  • Tenofovir
  • Creatinine
  • tenofovir alafenamide
  • Adenine
  • Alanine
Topics
  • Absorptiometry, Photon
  • Adenine (administration & dosage, analogs & derivatives, pharmacokinetics)
  • Administration, Oral
  • Adult
  • Alanine
  • Bone Density
  • CD4 Lymphocyte Count
  • Cholesterol (blood)
  • Creatinine (urine)
  • Double-Blind Method
  • Female
  • HIV Infections (drug therapy, metabolism, virology)
  • HIV-1 (isolation & purification)
  • Humans
  • Male
  • Prodrugs (administration & dosage, pharmacokinetics)
  • Proteinuria
  • RNA, Viral (blood)
  • Tenofovir (analogs & derivatives)
  • United States

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