• Anthony Mills, Gordon Crofoot, Cheryl McDonald, Peter Shalit, Jason A Flamm, Joseph Gathe, Anita Scribner, David Shamblaw, Michael Saag, Huyen Cao, Hal Martin, Moupali Das, Anne Thomas, Hui C Liu, Mingjin Yan, Christian Callebaut, Joseph Custodio, Andrew Cheng, and Scott McCallister.
• *Gordon Crofoot Research, Southern California Men's Medical Group/Men's Health Foundation, Assistant Professor of Clinical Medicine, Univeristy of California, Los Angeles, Los Angeles, CA; †Houston, TX; ‡Tarrant County Infectious Disease Associates, Fort Worth, TX; §Clinical Associate Professor in the Division of Allergy and Infectious Diseases, University of Washington School of Medicine, Seattle, WA; ‖Kaiser Permanente, Sacramento, CA; ¶Therapeutic Concepts, Houston, TX; #DCOL Center for Clinical Research, Longview, TX; **La Playa Medical Group and Clinical Research, San Diego, CA; ††Center for AIDS Research, The University of Alabama at Birmingham, Birmingham, AL; and ‡‡Gilead Sciences, Foster City, CA.
• J. Acquir. Immune Defic. Syndr. 2015 Aug 1; 69 (4): 439-45.

ObjectivesTo evaluate the safety and efficacy of the novel tenofovir prodrug, tenofovir alafenamide (TAF), as part of the first protease inhibitor-based single-tablet regimen (STR) for initial treatment of HIV-1 infection.MethodsAntiretroviral therapy (ART)-naive adults with estimated glomerular filtration rate ≥ 70 mL/min were randomized 2:1 to receive the darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) STR (TAF: N = 103) or darunavir + cobicistat + emtricitabine/tenofovir disoproxil fumarate (TDF: N = 50) once daily with matched placebos for 48 weeks.ResultsAt week 24, viral suppression (HIV-1 RNA <50 copies/mL) rates were similar (TAF 74.8% vs. TDF 74.0%). At week 48, rates were TAF 76.7% vs. TDF 84.0%; the difference was driven by higher rate of discontinuations in TAF (6.8%) vs. TDF (2%). Among those with virologic failure, none developed resistance. Most adverse events were of mild/moderate severity. The mean change in serum creatinine from baseline at week 48 was 0.06 mg/dL (95% confidence interval: 0.04 to 0.08) for TAF vs. 0.09 mg/dL (95% confidence interval: 0.05 to 0.14) for TDF (P = 0.053). The % change in retinol binding protein/Cr ratio was +9 (TAF) vs. +54 (TDF), P = 0.003; the % change in urine β-2 microglobulin/Cr ratio was -42.0 (TAF) vs. +2.3 (TDF), P = 0.002. The % change in hip bone mineral density (BMD) was -0.84 (TAF) vs. -3.82 (TDF), P < 0.001 and in spine BMD was -1.57 (TAF) vs. -3.62 (TDF), P = 0.003. There were no fractures in either group.ConclusionsThe TAF arm had significantly improved renal and bone safety parameters: less proteinuria and less change in hip and spine BMD, consistent with results from a similarly designed study of the elvitegravir/C/F/TAF STR. This D/C/F/TAF STR offers a promising option for initial HIV treatment, with the high barrier to resistance of darunavir, and the potential for improved long-term renal and bone safety with TAF.

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