Dolutegravir versus ritonavir-boosted lopinavir both with dual nucleoside reverse transcriptase inhibitor therapy in adults with HIV-1 infection in whom first-line therapy has failed (DAWNING): an open-label, non-inferiority, phase 3b trial
Dolutegravir versus ritonavir-boosted lopinavir both with dual nucleoside reverse transcriptase inhibitor therapy in adults with HIV-1 infection in whom first-line therapy has failed (DAWNING): an open-label, non-inferiority, phase 3b trial
复制标题
DOI：
10.1016/s1473-3099(19)30036-2
复制
发表时间：
2019-03-01
影响因子：
56.3
通讯作者：
Smith, Kimberly
中科院分区：
文献类型：
--
作者：
Aboud, Michael;Kaplan, Richard;Smith, Kimberly
背景对于在资源有限的环境中HIV-1感染患者的最佳二线治疗选择存在疑问。我们评估的安全性和有效性dolutegravir利托那韦相比，提高洛匹那韦，加两个核苷类逆转录酶抑制剂（NRTIs）在成人中，其中以前的一线抗逆转录病毒治疗与非核苷类逆转录酶抑制剂（NNRTI）加两个NRTIs已经failed.Methods黎明是一个3B期，开放标签，平行组，非劣效性，活性对照试验在13个国家的58个网站。符合条件的成人年龄至少为18岁，在接受包含一种NNRTI和两种NRTI的一线治疗至少6个月期间，病毒学失败（确认HIV-1 RNA ≥ 400拷贝/mL）。受试者由中心随机化系统随机分配接受口服dolutegravir（50 mg，每日一次）或利托那韦增强的洛匹那韦（800 mg洛匹那韦加200 mg利托那韦，每日一次或400 mg加100 mg，每日两次），加上两种药物选择的NRTI（根据筛选时的耐药性检测，至少一种完全有效）。主要结果是达到病毒抑制（定义为血浆HIV-1 RNA）的参与者比例
Background Doubts exist regarding optimal second-line treatment options for HIV-1-infected patients in resource-limited settings. We assessed safety and efficacy of dolutegravir compared with ritonavir-boosted lopinavir, plus two nucleoside reverse transcriptase inhibitors (NRTIs) in adults in whom previous first-line antiretroviral therapy with a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two NRTIs has failed.Methods DAWNING is a phase 3b, open-label, parallel-group, non-inferiority, active-controlled trial done at 58 sites in 13 countries. Eligible adults were aged at least 18 years and, during at least 6 months of treatment with a first-line treatment containing an NNRTI and two NRTIs, had virological failure (confirmed HIV-1 RNA >= 400 copies per mL). Participants were randomly assigned by a central randomisation system to receive oral dolutegravir (50 mg once daily) or ritonavir-boosted lopinavir (800 mg lopinavir plus 200 mg ritonavir once daily or 400 mg plus 100 mg twice daily), plus two investigator-selected NRTIs (at least one fully active based on resistance testing at screening). The primary outcome was the proportion of participants achieving viral suppression (defined as plasma HIV-1 RNA