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

TitleTenofovir alafenamide vs. tenofovir disoproxil fumarate in single tablet regimens for initial HIV-1 therapy: a randomized phase 2 study.
Publication TypeJournal Article
Year of Publication2014
AuthorsSax PE, Zolopa A, Brar I, Elion R, Ortiz R, Post F, Wang H, Callebaut C, Martin H, Fordyce MW, McCallister S
JournalJ Acquir Immune Defic Syndr
Volume67
Issue1
Pagination52-8
Date Published2014 Sep 01
ISSN1944-7884
KeywordsAbsorptiometry, Photon, Adenine, Administration, Oral, Adult, Bone Density, CD4 Lymphocyte Count, Cholesterol, Creatinine, Double-Blind Method, Female, HIV Infections, HIV-1, Humans, Male, Prodrugs, Proteinuria, RNA, Viral, United States
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.

DOI10.1097/QAI.0000000000000225
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID24872136