背景:由于感染HIV-2的个体数量较少,尚未进行过HIV-2治疗的随机试验。我们假设,一项描述平行组抗逆转录病毒治疗(ART)方案结果的非比较研究将提高对HIV-1和HIV-2之间的差异如何导致不同治疗方法的理解。
方法:这个飞行员,第二阶段,非比较性,开放标签,随机对照试验在布基纳法索进行,科特迪瓦,塞内加尔,还有多哥.未接受ART且CD4计数为200个细胞/μL或更高的HIV-2成人被随机分配为1:1:1至三个治疗组之一。计算机生成的按国家分层的顺序编号的块随机化列表用于在线分配到下一个可用的治疗组。在所有组中,富马酸替诺福韦酯(以下简称替诺福韦)的剂量为245mg,每天一次,恩曲他滨200mg,每天一次,拉米夫定300mg,每天一次。三核苷逆转录酶抑制剂(NRTI)组每天两次接受250mg的齐多夫定。利托那韦增强的洛匹那韦治疗组每天两次接受400毫克的洛匹那韦,每天两次接受100毫克的利托那韦。raltegravir组接受raltegravir400mg每日两次。主要结果是96周时的治疗成功率,定义为随访期间无严重发病事件,在第96周,血浆HIV-2RNA少于50个拷贝/mL,并且在基线和第96周之间CD4细胞大幅增加。该试验在ClinicalTrials.gov注册,NCT02150993,并对新参与者关闭。
结果:在2016年1月26日至2017年6月29日之间,210名参与者被随机分配到治疗组。5名参与者在96周的随访中死亡(三重NRTI组,n=2;利托那韦增强的洛匹那韦组,n=2;拉特格韦组,n=1),八人发生了严重的发病事件(三重NRTI组,n=4;利托那韦增强的洛匹那韦组,n=3;拉特格韦组,n=1),17人的血浆HIV-2RNA为50拷贝/mL或更高至少一次(三重NRTI组,n=11;利托那韦增强的洛匹那韦组,n=4;拉特格韦组,n=2),32(全部在三重NRTI组中)切换到另一种ART方案,和18永久停止ART(三重NRTI组,n=5;利托那韦增强的洛匹那韦组,n=7;拉特格韦组,n=6)。出于安全原因,数据安全监测委员会建议提前终止三重NRTI方案。利托那韦增强的洛匹那韦组的总体治疗成功率为57%(95%CI47-66),雷替格韦组为59%(49-68)。
结论:雷替格韦和利托那韦增强的洛匹那韦方案在HIV-2成人中是有效和安全的。这两种方案可以在未来的3期试验中进行比较。这项初步研究的结果表明,在基于raltegravir的方案中,病毒学和免疫学疗效更好的趋势。
背景:ANRSMIE。
BACKGROUND: Due to the low number of individuals with HIV-2, no randomised trials of HIV-2 treatment have ever been done. We hypothesised that a non-comparative study describing the outcomes of several antiretroviral therapy (ART) regimens in parallel groups would improve understanding of how differences between HIV-1 and HIV-2 might lead to different therapeutic approaches.
METHODS: This pilot, phase 2, non-comparative, open-label, randomised controlled trial was done in Burkina Faso, Côte d\'Ivoire, Senegal, and Togo. Adults with HIV-2 who were ART naive with CD4 counts of 200 cells per μL or greater were randomly assigned 1:1:1 to one of three treatment groups. A computer-generated sequentially numbered block randomisation list stratified by country was used for online allocation to the next available treatment group. In all groups, tenofovir disoproxil fumarate (henceforth tenofovir) was dosed at 245 mg once daily with either emtricitabine at 200 mg once daily or lamivudine at 300 mg once daily. The triple nucleoside reverse transcriptase inhibitor (NRTI) group received zidovudine at 250 mg twice daily. The ritonavir-boosted lopinavir group received lopinavir at 400 mg twice daily boosted with ritonavir at 100 mg twice daily. The raltegravir group received raltegravir at 400 mg twice daily. The primary outcome was the rate of treatment success at week 96, defined as an absence of serious morbidity event during follow-up, plasma HIV-2 RNA less than 50 copies per mL at week 96, and a substantial increase in CD4 cells between baseline and week 96. This trial is registered at ClinicalTrials.gov, NCT02150993, and is closed to new participants.
RESULTS: Between Jan 26, 2016, and June 29, 2017, 210 participants were randomly assigned to treatment groups. Five participants died during the 96 weeks of follow-up (triple NRTI group, n=2; ritonavir-boosted lopinavir group, n=2; and raltegravir group, n=1), eight had a serious morbidity event (triple NRTI group, n=4; ritonavir-boosted lopinavir group, n=3; and raltegravir group, n=1), 17 had plasma HIV-2 RNA of 50 copies per mL or greater at least once (triple NRTI group, n=11; ritonavir-boosted lopinavir group, n=4; and raltegravir group, n=2), 32 (all in the triple NRTI group) switched to another ART regimen, and 18 permanently discontinued ART (triple NRTI group, n=5; ritonavir-boosted lopinavir group, n=7; and raltegravir group, n=6). The Data Safety Monitoring Board recommended premature termination of the triple NRTI regimen for safety reasons. The overall treatment success rate was 57% (95% CI 47-66) in the ritonavir-boosted lopinavir group and 59% (49-68) in the raltegravir group.
CONCLUSIONS: The raltegravir and ritonavir-boosted lopinavir regimens were efficient and safe in adults with HIV-2. Both regimens could be compared in future phase 3 trials. The results of this pilot study suggest a trend towards better virological and immunological efficacy in the raltegravir-based regimen.
BACKGROUND: ANRS MIE.