Castagna Antonella, Maggiolo Franco, Penco Giovanni, Wright David, Mills Anthony, Grossberg Robert, Molina Jean-Michel, Chas Julie, Durant Jacques, Moreno Santiago, Doroana Manuela, Ait-Khaled Mounir, Huang Jenny, Min Sherene, Song Ivy, Vavro Cindy, Nichols Garrett, Yeo Jane M
San Raffaele Scientific Institute, Milan.
Ospedale Riuniti, Bergamo.
J Infect Dis. 2014 Aug 1;210(3):354-62. doi: 10.1093/infdis/jiu051. Epub 2014 Jan 19.
The pilot phase IIb VIKING study suggested that dolutegravir (DTG), a human immunodeficiency virus (HIV) integrase inhibitor (INI), would be efficacious in INI-resistant patients at the 50 mg twice daily (BID) dose.
VIKING-3 is a single-arm, open-label phase III study in which therapy-experienced adults with INI-resistant virus received DTG 50 mg BID while continuing their failing regimen (without raltegravir or elvitegravir) through day 7, after which the regimen was optimized with ≥1 fully active drug and DTG continued. The primary efficacy endpoints were the mean change from baseline in plasma HIV-1 RNA at day 8 and the proportion of subjects with HIV-1 RNA <50 c/mL at week 24.
Mean change in HIV-1 RNA at day 8 was -1.43 log10 c/mL, and 69% of subjects achieved <50 c/mL at week 24. Multivariate analyses demonstrated a strong association between baseline DTG susceptibility and response. Response was most reduced in subjects with Q148 + ≥2 resistance-associated mutations. DTG 50 mg BID had a low (3%) discontinuation rate due to adverse events, similar to INI-naive subjects receiving DTG 50 mg once daily.
DTG 50 mg BID-based therapy was effective in this highly treatment-experienced population with INI-resistant virus.
www.clinicaltrials.gov (NCT01328041) and http://www.gsk-clinicalstudywww.gsk-clinicalstudyregister.com (112574).
IIb期VIKING先导研究表明，度鲁特韦（DTG），一种人类免疫缺陷病毒（HIV）整合酶抑制剂（INI），对于INI耐药患者，每日两次、每次50mg的剂量将是有效的。
VIKING-3是一项单臂、开放标签的III期研究，其中有INI耐药病毒的有治疗经验的成年人接受每日两次、每次50mg的DTG治疗，同时在第7天之前继续使用其失败的治疗方案（不包括raltegravir或elvitegravir），之后用≥1种完全有效的药物优化治疗方案并继续使用DTG。主要疗效终点是第8天血浆HIV-1 RNA相对于基线的平均变化以及第24周时HIV-1 RNA<50拷贝/mL的受试者比例。
第8天HIV-1 RNA的平均变化为-1.43 log10拷贝/mL，69%的受试者在第24周时达到<50拷贝/mL。多变量分析表明基线DTG敏感性与反应之间存在强关联。在具有Q148 +≥2个耐药相关突变的受试者中反应降低最为明显。每日两次、每次50mg的DTG因不良事件导致的停药率较低（3%），与接受每日一次、每次50mg DTG的初治受试者相似。
基于每日两次、每次50mg DTG的治疗方案在这个具有INI耐药病毒的高度有治疗经验的人群中是有效的。
