Specialist Virology Centre, Royal Infirmary of Edinburgh and University of Edinburgh, Edinburgh.
Barts Health NHS Trust and Queen Mary University of London, London, UK.
Curr Opin HIV AIDS. 2018 Jul;13(4):315-319. doi: 10.1097/COH.0000000000000465.
In an era when virological efficacy approaches 100%, novel antiretroviral (ARV) therapies must deliver better tolerability, safety, and convenient coformulated regimens. We review the phase II and III clinical data on the fixed dose combination (FDC) darunavir (DRV) 800mg / cobicistat (COBI/C) 150 mg / emtricitabine (F/FTC) 200 mg / tenofovir alafenamide fumarate (TAF) 10mg (D/C/F/TAF) for the treatment of HIV-1 infection.
In an exploratory phase II study, D/C/F/TAF FDC demonstrated similar virological efficacy to darunavir/cobicistat FDC + F /tenofovir disoproxil fumarate (TDF) FDC in treatment-naive HIV-1-infected individuals with favorable bone and renal outcomes. These findings led to two subsequent international phase III double-blind randomized controlled trials; AMBER and EMERALD. In the (treatment naïve) AMBER study, D/C/F/TAF FDC was noninferior to component regimen F/TDF + darunavir/cobicistat with favorable bone and renal outcomes at week 48. In the EMERALD study (switch study for virologically suppressed patients), D/C/F/TAF showed noninferior efficacy to F/TDF and boosted protease inhibitor (bPI) regimen at week 48 also with favorable renal and bone outcomes. No virological failure was observed, and no resistance to TDF or darunavir emerged in either study.
In clinical trials, D/C/F/TAF FDC demonstrated excellent, noninferior virological efficacy, maintained a high genetic barrier and conferred the additional safety benefits of TAF. As the first one pill, once daily, protease inhibitor-based regimen, D/C/F/TAF FDC offers a new option for the treatment of HIV infection.
在病毒学疗效接近 100%的时代，新型抗逆转录病毒（ARV）治疗必须具有更好的耐受性、安全性和方便的联合配方。我们回顾了固定剂量复方（FDC）达芦那韦（DRV）800mg/考比司他（COBI/C）150mg/恩曲他滨（F/FTC）200mg/富马酸替诺福韦艾拉酚胺（TAF）10mg（D/C/F/TAF）治疗 HIV-1 感染的 II 期和 III 期临床数据。
在一项探索性 II 期研究中，D/C/F/TAF FDC 在治疗初治 HIV-1 感染的个体中，与达芦那韦/考比司他 FDC+F/富马酸替诺福韦二吡呋酯（TDF）FDC 相比，具有相似的病毒学疗效，且具有良好的骨骼和肾脏结局。这些发现导致了随后进行的两项国际 III 期双盲随机对照试验；AMBER 和 EMERALD。在（初治）AMBER 研究中，D/C/F/TAF FDC 与 F/TDF+达芦那韦/考比司他的对照组相比非劣效，在第 48 周时具有良好的骨骼和肾脏结局。在 EMERALD 研究（病毒抑制患者转换研究）中，D/C/F/TAF 在第 48 周时显示出与 F/TDF 和增效蛋白酶抑制剂（bPI）方案非劣效的疗效，并且肾脏和骨骼结局也良好。在这两项研究中，均未观察到病毒学失败，也未出现对 TDF 或达芦那韦的耐药性。
在临床试验中，D/C/F/TAF FDC 表现出优异的、非劣效的病毒学疗效，保持了较高的遗传屏障，并具有 TAF 带来的额外安全性益处。作为首个每日 1 片、基于蛋白酶抑制剂的治疗方案，D/C/F/TAF FDC 为 HIV 感染的治疗提供了新的选择。
