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.
*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.
Correspondence to: Hal Martin, MD, MPH, Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404 (e-mail: firstname.lastname@example.org).
Supported by Gilead Sciences, Foster City, CA.
P.E.S., A.Z., I.B., R.E., and R.O. enrolled patients and reviewed and interpreted analyses of data. S.M., M.W.F., C.C., and H.W. designed the study. Data collection was overseen by H.W., C.C., H.M., M.W.F., and S.M. H.W. analyzed data, which were reviewed and interpreted by C.C., H.M., M.F., and S.M. The first draft of this report was written by P.E.S., H.M., M.F., and S.M. The draft report was edited by P.E.S., A.Z., I.B., R.E., and R.O.
P.E.S.: Consultant or Scientific Advisory Board member: Abbott, BMS, Gilead, GSK, Merck, Janssen; Grant support for research: BMS, Gilead, GSK. A.Z.: Funding: Gilead. I.B.: Speakers Bureau: Gilead, Funding: Gilead, Merck, Viiv, Stock: Gilead. R.E.: Advisory Panels: Gilead, BMS, Jannsen, ViiV, Speakers Bureaus: Gilead, BMS, Jannsen, ViiV, Merck, Research Grants: Gilead, AbbVie, BMS, ViiV. R.O.: Speaker's bureaus: Gilead, BMS, Funding: Gilead. H.W., C.C., H.M., M.W.F., S.M. are Employees of Gilead Sciences.
Abstract presented by Dr Paul Sax, during 53rd Annual ICAAC Conference, September 10–13, 2013, Denver, CO.
Received January 24, 2014
Accepted May 05, 2014