多拉韦林/拉米夫定/替诺福韦转换治疗HIV-1高病毒学抑制患者48周临床试验:DRIVE-SHIFT最新报道

Switching to doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) treats HIV-1 patients with high virologic suppression through 48 weeks’ trail: the latest report of DRIVE-SHIFT

目的评估多拉韦林拉米夫定替诺福韦片(doravirine/lamivudine/tenofovir disoproxil fumarate,DOR/3TC/TDF)治疗HIV病毒学抑制≥6个月的HIV-1成年感染者的有效性和安全性。方法此项开放性标签、活性对照、非劣效性临床试验中,经过2种核苷类逆转录酶抑制剂加1种增强型蛋白酶抑制剂、增强型艾维雷韦或1种非核苷类逆转录酶抑制剂治疗后的HIV病毒学抑制≥6个月的HIV-1成年感染者,按照2:1比例随机分组,一组为改用每日1次DOR/3TC/TDF方案试验组,另一组为继续基线方案24周的对照组。主要终点是第48周DOR/3TC/TDF试验组与第24周基线方案对照组间HIV-1 RNA<50拷贝/mL的受试者比例差异,次要终点是第24周时两组间获得病毒学应答的受试者比例差异(非劣效界值,-8%)。结果670例受试者(DOR/3TC/TDF组447例,基线方案组223例)纳入了分析。24周时,HIV-1 RNA<50拷贝/mL的患者在DOR/3TC/TDF组占比为93.7%,基线方案组中为94.6%[差异-0.9(-4.7~3.0)]。48周时,DOR/3TC/TDF组中HIV-1 RNA<50拷贝/mL受试者占比仍为90.8%,非劣效于24周时基线方案组[差异-3.8(-7.9~0.3)]。在曾接受过利托那韦增强型蛋白酶抑制剂治疗的试验组中,24周时其空腹低密度脂蛋白胆固醇和非高密度脂蛋白胆固醇的平均降幅显著高于基线方案对照组(P<0.01)。第24周时,试验组和对照组的不良事件发生率分别为68.9%和52.5%,导致治疗停止的不良事件发生率分别为2.5%和0.4%。结论对于需改变治疗的患者,转换到每日1次的DOR/3TC/TDF方案是一种耐受性良好且可维持病毒学抑制的选择。

Objective To evaluate the efficacy and safety of Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate(DOR/3TC/TDF)in adults with HIV-1 virologically suppressed for≥6 months.Methods In this open-label,active-controlled,noninferiority trial,adults with HIV-1 virologically suppressed for≥6 months on 2 nucleoside reverse transcriptase inhibitors plus a boosted protease inhibitor,boosted elvitegravir,or a non-nucleoside reverse transcriptase inhibitor were randomized(2:1)to switch to once-daily,single-tablet doravirine 100 mg with lamivudine 300 mg and tenofovir disoproxil fumarate 300 mg(DOR/3TC/TDF)or to continue their current therapy(Baseline Regimen)for 24 weeks.The primary endpoint was the proportion of participants with HIV-1 RNA<50 copies/mL,with the primary comparison between DOR/3TC/TDF at week 48 and Baseline Regimen at week 24 and a secondary comparison between the groups at week 24(noninferiority margin,-8%).Results Six hundred seventy participants(447 DOR/3TC/TDF,223 Baseline Regimen)were treated and included in the analyses.At week 24,93.7%on DOR/3TC/TDF vs 94.6%on Baseline Regimen had HIV-1 RNA<50 copies/mL[difference-0.9(-4.7 to 3.0)].At week 48,90.8%on DOR/3TC/TDF had HIV-1 RNA<50 copies/mL,demonstrating noninferiority vs Baseline Regimen at week 24[difference-3.8(-7.9 to 0.3)].In participants on ritonavir-boosted protease inhibitor at entry,mean reductions in fasting LDL-C and non-HDL-C at week 24 were significantly greater for DOR/3TC/TDF vs Baseline Regimen(P<0.01).Adverse events occurred in 68.9%on DOR/3TC/TDF and 52.5%on Baseline Regimen by week 24,leading to treatment discontinuation in 2.5%and 0.4%,respectively.Conclusions Switching to once-daily DOR/3TC/TDF is a generally well-tolerated option for maintaining viral suppression in patients considering a change in therapy.