West Virginia University Health Sciences Center, Morgantown, WV.
Division of Infectious Diseases, Thomas Jefferson University, Philadelphia, PA.
J Acquir Immune Defic Syndr. 2018 Jun 1;78(2):209-213. doi: 10.1097/QAI.0000000000001663.
The integrase inhibitor regimen [elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (TDF)] demonstrated superior efficacy when compared with a protease inhibitor regimen [ritonavir-boosted atazanavir (ATV + RTV) and FTC/TDF] in 575 treatment-naive women at week 48. We investigated the efficacy, safety, and tolerability of switching to a TAF-based, single-tablet regimen containing elvitegravir, cobicistat, FTC, and tenofovir alafenamide (E/C/F/TAF) versus remaining on ATV + RTV plus FTC/TDF.
After completing the initial randomized, blinded phase, virologically suppressed (HIV-1 RNA <50 copies/mL) women on ATV + RTV plus FTC/TDF were rerandomized (3:1) to receive open-label E/C/F/TAF versus remaining on their current regimen. The primary end point was proportion of participants with plasma HIV-1 RNA <50 copies per milliliter at week 48 (U.S. FDA snapshot algorithm), with a prespecified noninferiority margin of 12%. Safety [adverse events (AEs)] and tolerability were also assessed.
Of 575 women originally randomized and treated in the blinded phase, 159 were rerandomized to switch to E/C/F/TAF and 53 to remain on ATV + RTV plus FTC/TDF. At week 48, virologic suppression was maintained in 150 (94%) of women on E/C/F/TAF and 46 (87%) on ATV + RTV plus FTC/TDF [difference 7.5% (95% confidence interval -1.2% to 19.4%)], demonstrating noninferiority of E/C/F/TAF to ATV + RTV and FTC/TDF. Incidence of AEs was similar between groups; study drug-related AEs were more common with E/C/F/TAF (11% versus 4%).
Switching to E/C/F/TAF was noninferior to continuing ATV + RTV plus FTC/TDF in maintaining virologic suppression and was well tolerated at 48 weeks.
在 575 名初治女性中,与蛋白酶抑制剂方案[利托那韦增强的阿扎那韦(ATV + RTV)和 FTC/TDF]相比,整合酶抑制剂方案[艾维雷格韦/考比司他/恩曲他滨/替诺福韦富马酸二吡呋酯(TDF)]在第 48 周时显示出更优的疗效。我们研究了转换为含艾维雷格韦、考比司他、FTC 和替诺福韦艾拉酚胺(E/C/F/TAF)的 TAF 为基础的单片方案与继续使用 ATV + RTV 加 FTC/TDF 的疗效、安全性和耐受性。
在完成初始随机、双盲阶段后,接受 ATV + RTV 加 FTC/TDF 治疗且病毒载量抑制(HIV-1 RNA<50 拷贝/mL)的女性被重新随机(3:1)接受开放标签的 E/C/F/TAF 或继续使用其现有方案。主要终点是第 48 周时血浆 HIV-1 RNA<50 拷贝/毫升的参与者比例(美国 FDA 快照算法),预设非劣效性边界为 12%。还评估了安全性[不良事件(AE)]和耐受性。
在最初接受随机分组和双盲阶段治疗的 575 名女性中,有 159 名被重新随机分配至 E/C/F/TAF 组,53 名继续接受 ATV + RTV 加 FTC/TDF 治疗。在第 48 周时,E/C/F/TAF 组 150 名(94%)女性和 ATV + RTV 加 FTC/TDF 组 46 名(87%)女性维持病毒学抑制[差异 7.5%(95%置信区间-1.2%至 19.4%)],表明 E/C/F/TAF 不劣于 ATV + RTV 和 FTC/TDF。两组的不良事件发生率相似;E/C/F/TAF 组更常见与研究药物相关的不良事件(11%比 4%)。
在第 48 周时,转换为 E/C/F/TAF 与继续使用 ATV + RTV 加 FTC/TDF 维持病毒学抑制效果相当,且耐受性良好。