Randomized, phase 2 evaluation of two single-tablet regimens elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for the initial treatment of HIV infection
Randomized, phase 2 evaluation of two single-tablet regimens elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for the initial treatment of HIV infection
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DOI：
10.1097/qad.0b013e328345766f
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发表时间：
2011-03-27
期刊：
影响因子：
3.8
通讯作者：
Kearney, Brian P.
中科院分区：
文献类型：
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作者：
Cohen, Calvin;Elion, Richard;Kearney, Brian P.
目的：设计：2期、随机、双盲、双模拟、多中心、活性对照研究。方法：将筛选HIV-1 RNA至少为5000拷贝/ml且CD 4细胞计数超过50个细胞/μ l的抗逆转录病毒治疗初治成人随机分为2组：1例患者接受埃替拉韦/可比司他/恩曲他滨/富马酸替诺福韦酯（EVG/COBI/FTC/TDF; N = 48）或依法韦仑/恩曲他滨/富马酸替诺福韦酯（EFV/FTC/TDF; n = 23）的固定剂量复方片剂治疗48周。主要终点是第24周HIV-1 RNA低于50拷贝/ml的受试者比例。结果：与接受EFV/FTC/TDF的受试者相比，接受EVG/COBI/FTC/TDF的受试者表现出更快的HIV-1 RNA下降，更大比例的病毒载量被抑制至低于50拷贝/ml。EVG/COBI/FTC/TDF和EFV/FTC/TDF均导致高病毒抑制率和CD 4细胞计数增加。在EVG/COBI/FTC/TDF和EFV/FTC/TDF的24周和48周访视时，分别有90%和83%的受试者将HIV-1 RNA抑制至低于50拷贝/ml。在研究访视期间，EVG/COBI/FTC/TDF每日一次给药提供的平均EVG谷浓度是其蛋白结合校正IC 95的10倍。EVG/FTC/TDF/GS-9350通常耐受性良好，与EFV/FTC/TDF（分别为26%和44%）相比，药物相关中枢神经系统（17%）和精神（10%）不良事件的发生率较低。在接受EVG/COBI/FTC/TDF的参与者中，估计的肾小球滤过率下降发生在给药的前几周内，保持在正常范围内，并且在第24周或第48周没有进展;没有参与者经历临床不良事件或由于血清肌酐或肾功能变化而停用研究药物。每日一次EVG/COBI/FTC/TDF实现并维持了较高的病毒学抑制率，与当前标准治疗方案EFV/FTC/TDF相比，中枢神经系统和精神病不良事件较少。(c)2011年威科健康|利平科特威廉姆斯&威尔金斯
Objective: To assess the safety and efficacy of two, single-tablet regimens for the initial treatment of HIV infection.Design: Phase 2, randomized, double-blind, double-dummy, multicenter, active-controlled study.Methods: Antiretroviral treatment-naive adults with a screening HIV-1 RNA at least 5000 copies/ml and a CD4 cell count more than 50 cells/mu l were randomized 2 : 1 to receive fixed-dose combination tablets of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF; N = 48) or efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF; n = 23) for 48 weeks. The primary endpoint was proportion of participants with HIV-1 RNA less than 50 copies/ml at week 24.Results: Participants receiving EVG/COBI/FTC/TDF exhibited a more rapid decline in HIV-1 RNA and a greater proportion suppressed viral load to less than 50 copies/ml than participants receiving EFV/FTC/TDF. Both EVG/COBI/FTC/TDF and EFV/FTC/TDF resulted in high rates of viral suppression and increases in CD4 cell count. Ninety and 83% of participants suppressed HIV-1 RNA to less than 50 copies/ml both at the 24-week and 48-week visits for EVG/COBI/FTC/TDF and EFV/FTC/TDF, respectively. Once-daily administration of EVG/COBI/FTC/TDF provided a mean EVG trough concentration 10-fold over its protein binding-adjusted IC95 across study visits. EVG/FTC/TDF/GS-9350 was generally well tolerated with a lower rate of drug-related central nervous system (17%) and psychiatric (10%) adverse events versus EFV/FTC/TDF (26 and 44%, respectively). Decreases in estimated glomerular filtration rate occurred within the first few weeks of dosing in participants receiving EVG/COBI/FTC/TDF, remained within the normal range and did not progress at week 24 or 48; no participant experienced a clinical adverse event or discontinued study drug due to changes in serum creatinine or renal function.Conclusion: Once-daily EVG/COBI/FTC/TDF achieved and maintained a high rate of virologic suppression with fewer central nervous system and psychiatric adverse events compared to a current standard-of-care regimen of EFV/FTC/TDF. (c) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins