Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate in the First Protease Inhibitor–Based Single-Tablet Regimen for Initial HIV-1 Therapy

作者：Anthony Mills, Gordon Crofoot, Cheryl McDonald, Peter Shalit, Jason Flamm, Joseph Gathe, Anita Scribner, David Shamblaw, Michael S. Saag, Huyen Cao, Hal Martin, Moupali Das, Anne Thomas, Hui C. Liu, Mingjin Yan, Christian Callebaut, Joseph M. Custodio, Andrew Cheng, Scott McCallister · 发表于：JAIDS Journal of Acquired Immune Deficiency Syndromes · 年份：2015 · DOI：10.1097/qai.0000000000000618 · 被引用次数：140 · 研究领域：HIV/AIDS drug development and treatment、HIV/AIDS Research and Interventions、HIV Research and Treatment

OBJECTIVES: To 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. METHODS: Antiretroviral 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. RESULTS: At 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 fractu...