A Randomized, Open-Label Trial to Evaluate Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Plus Darunavir in Treatment-Experienced HIV-1-Infected Adults.
A Randomized, Open-Label Trial to Evaluate Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Plus Darunavir in Treatment-Experienced HIV-1-Infected Adults.
复制标题
DOI：
10.1097/qai.0000000000001193
复制
发表时间：
2017-02-01
期刊：
影响因子：
--
通讯作者：
McCallister S
中科院分区：
文献类型：
--
作者：
Huhn GD;Tebas P;Gallant J;Wilkin T;Cheng A;Yan M;Zhong L;Callebaut C;Custodio JM;Fordyce MW;Das M;McCallister S
补充数字内容在文本中可用。有既往耐药和方案失败史的HIV感染、有治疗经验的成人患者可以进行病毒学抑制，但可能需要与依从性较低和潜在耐药发展相关的多片剂方案。我们招募了HIV感染、病毒学抑制、2级至3级耐药且至少有2次既往治疗方案失败的成年患者参加这项3期、开放标签、随机研究。主要终点是第24周时HIV-1 RNA <50拷贝/毫升的参与者百分比[食品和药物管理局（FDA）快照算法]。135例受试者[埃替拉韦/可比司他/恩曲他滨/替诺福韦艾拉酚胺（E/C/F/TAF）+地瑞那韦（DRV），n = 89;基线方案，n = 46]，其中大多数患者的中位剂量为5片/天，简化为E/C/F/TAF + DRV在第24周时非劣效于继续基线方案（血浆HIV-1 RNA <50拷贝/毫升：96.6% vs. 91.3%，差异5.3%，95.001% CI：−3.4%至17.4%）。对于相同结局，E/C/F/TAF + DRV在第48周时符合预先规定的非劣效性和优效性标准。与基线方案相比，E/C/F/TAF + DRV耐受性良好，肾脏安全性特征改善，两组间定量总蛋白尿和近端肾小管蛋白尿标志物的差异具有统计学意义。与基线方案相比，转换为E/C/F/TAF + DRV的参与者报告了更高的平均治疗满意度量表总分和更少的漏服剂量天数。本研究表明，方案从5片方案简化为2片、每日一次的E/C/F/TAF + DRV联合治疗可持久维持病毒学抑制，并改善肾脏安全性的特定标志物。这种策略可能会导致更大的依从性和改善生活质量。
Supplemental Digital Content is Available in the Text. HIV-infected, treatment-experienced adults with a history of prior resistance and regimen failure can be virologically suppressed but may require multitablet regimens associated with lower adherence and potential resistance development. We enrolled HIV-infected, virologically suppressed adults with 2-class to 3-class drug resistance and at least 2 prior regimen failures into this phase 3, open-label, randomized study. The primary endpoint was the percentage of participants with HIV-1 RNA <50 copies per milliliter at week 24 [Food and Drug Administration (FDA) snapshot algorithm]. For 135 participants [elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) plus darunavir (DRV), n = 89; baseline regimen, n = 46], most of whom were taking a median of 5 tablets/d, simplification to E/C/F/TAF plus DRV was noninferior to continuation of baseline regimens at week 24 (plasma HIV-1 RNA <50 copies per milliliter: 96.6% vs. 91.3%, difference 5.3%, 95.001% CI: −3.4% to 17.4%). E/C/F/TAF plus DRV met prespecified criteria for noninferiority and superiority at week 48 for the same outcome. E/C/F/TAF plus DRV was well tolerated and had an improved renal safety profile compared with baseline regimens, with statistically significant differences between groups in quantitative total proteinuria and markers of proximal tubular proteinuria. Compared with baseline regimens, participants who switched to E/C/F/TAF plus DRV reported higher mean treatment satisfaction scale total scores and fewer days with missed doses. This study demonstrated that regimen simplification from a 5-tablet regimen to the 2-tablet, once-daily combination of E/C/F/TAF plus DRV has durable maintenance of virologic suppression and improvements in specific markers of renal safety. Such a strategy may lead to greater adherence and improved quality of life.