Objectives: To evaluate the safety and efficacy of the novel tenofovir prodrug, tenofovir alafenamide (TAF), as part of a single tablet regimen (STR) for 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 >= 5,000 copies/mL and CD4 count >= 50 cells/[micro]L were randomized 2:1 to receive a single-tablet regimen 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/mL) 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 AEs 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 mL/min 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, LDL and HDL, but the total cholesterol/HDL ratio was unchanged for both.
Conclusion: Treatment naive patients treated with an STR that contained either TAF or TDF achieved a high rate of virologic success. Compared to those receiving TDF, patients on E/C/F/TAF experienced significantly smaller changes in estimated creatinine clearance, renal tubular proteinuria, and bone mineral density.
(C) 2014 by Lippincott Williams & Wilkins