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

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

Author information

1
*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.

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.

PMID:
24872136
DOI:
10.1097/QAI.0000000000000225
[Indexed for MEDLINE]
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