Rare emergence of drug resistance in HIV-1 treatment-naive patients receiving elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide for 144 weeks
Rare emergence of drug resistance in HIV-1 treatment-naive patients receiving elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide for 144 weeks
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DOI：
10.1016/j.jcv.2018.03.012
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发表时间：
2018-06-01
影响因子：
8.8
通讯作者：
Callebaut, Christian
中科院分区：
文献类型：
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作者：
Margot, Nicolas;Cox, Stephanie;Callebaut, Christian
背景：在1733例HIV-1感染治疗初期成人的2期3期研究中，比较了由elvitegravir(E)、替比西斯特(C)、恩曲他滨(F)和替诺福韦丙氨酰胺(TAF)组成的单一片剂方案(E/C/F/TAF)和由E、C、F和替诺福韦富马酸酯(TDF)组成的STR(E/C/F/TDF)。与E/C/F/TDF相比，E/C/F/TAF在144周时显示出更好的疗效，治疗成功率分别为84%和80%，并且骨和肾脏安全的结果显著改善。目的：分析接受E/C/F/TAF治疗144周的未接受治疗的成年人出现HIV-1耐药性的情况。研究设计：我们进行了2个阶段3研究的综合耐药性分析，包括所有参与者的HIV-1预先测序(N=1733)和有病毒学失败的参与者的基线后HIV-1耐药性分析(HIV-1RNA和GT；结果：入选受试者治疗前有7.4%(NRTI-RAMS)、18.1%(NNRTI-RAMS)和3.3%(PI-RAMS)出现原发耐药相关突变(RAMS)。在第144周，基线HIV-1亚型或先前存在的RAMS不影响E/C/F/TAF治疗反应。在E/C/F/TAF和E/C/F/TDF组中，分别有28/866(3.2%)和30/867(3.5%)患者进行了病毒学耐药分析。在三年的研究中，每组的耐药发生率保持在1.4%的低水平(E/C/F/TAF组12/866；E/C/F/TDF组12/867)。在24例对抗逆转录病毒药物产生耐药性的患者中出现了耐药病毒(E/C/F/TAF：M184V/I[1.3%]，INSTI-RAMS[0.9%]，K65R/N[0.2%]；E/C/F/TDF：M184V/I[1.0%]，INSTI-RAMS[0.9%]，K65R/N[0.5%])。M184V/i是最流行的RAM(总共1.2%)。
Background: The single tablet regimen (STR) composed of elvitegravir (E), cobicistat (C), emtricitabine (F), and tenofovir alafenamide (TAF) (E/C/F/TAF) was compared to the STR composed of E, C, F, and tenofovir disoproxil fumarate (TDF) (E/C/F/TDF) in 2 phase 3 studies in 1733 HIV-1 infected treatment-naive adults. Superior efficacy of E/C/F/TAF compared to E/C/F/TDF was demonstrated at Week 144 with 84% treatment success compared to 80%, respectively, along with significantly better outcomes of bone and renal safety.Objectives: Analyze the emergence of HIV-1 resistance in treatment-naive adults receiving E/C/F/TAF for 144 weeks.Study design: We conducted an integrated resistance analysis of the 2 Phase 3 studies, comprising pretreatment HIV-1 sequencing for all participants (N = 1733) and post-baseline HIV-1 resistance analysis for participants with virologic failure (HIV-1 RNA >= 400 copies/mL).Results: Primary resistance associated mutations (RAMs) were observed pre-treatment in 7.4% (NRTI-RAMs), 18.1% (NNRTI-RAMs), and 3.3% (PI-RAMs) of enrolled subjects. Baseline HIV-1 subtype or pre-existing RAMs did not affect E/C/F/TAF treatment response at week 144. Virologic failure resistance analyses were conducted for 28/866 (3.2%) and 30/867 (3.5%) patients in the E/C/F/TAF and E/C/F/TDF arms, respectively. Over the 3-year study, the rate of resistance emergence remained low at 1.4% in each group (12/866 in E/C/F/TAF; 12/867 in E/C/F/TDF). Resistant virus emerged in 24 patients who developed resistance to antiretrovirals in the regimens (E/C/F/TAF: M184V/I [1.3%], INSTI-RAMs [0.9%], K65R/N [0.2%]; E/C/F/TDF: M184V/I [1.0%], INSTI-RAMs [0.9%], K65R/N [0.5%]).Conclusions: Resistance emergence was rare (1.4%) with similar patterns of emergent mutations in both groups. M184V/I was the most prevalent RAM (1.2% overall).