■我们比较了ainuvirine(ANV)的疗效和安全性,新一代非核苷逆转录酶抑制剂(NNRTI),用增强的elvitegravir(EVG),两者都与两种核苷逆转录酶抑制剂(NRTIs)共同配制,在HIV-1(PLWH)感染者中,在以前基于NNRTI的抗逆转录病毒(ARV)方案中实现了病毒学抑制。
■这项研究是一项多中心研究,随机化,双盲,主动控制,非劣效性试验从中国10个临床中心招募PLWH。主要纳入标准包括年龄18-65岁(含),并在结合NNRTI和两种药物NRTI骨架的ARV方案下稳定停留至少12个月。符合条件的参与者必须在随机化前至少一个月的间隔内,在两次连续测试中确认的血浆HIV-1核糖核酸(RNA)滴度保持在每毫升50拷贝以下。参与者被随机分配接受ANV150毫克加拉米夫定(3TC)300毫克,和富马酸替诺福韦酯(TDF)300毫克(ANV/3TC/TDF),或cobicistat(Cobi)150毫克加强EVG加恩曲他滨(FTC)200毫克,和替诺福韦艾拉酚胺(TAF)10毫克。主要疗效终点是使用美国食品和药物管理局快照算法在第48周时HIV-1RNA滴度为50拷贝/mL或以上的参与者比例。在双方95%的置信水平下,非劣效性为4个百分点。这次审判很活跃,但不是招募,并在中国临床试验注册中心(ChiCTR)注册,编号ChiCTR2100051605。
■在2021年10月至2022年2月之间,对923名患者进行了资格筛选。其中762例参与者被随机分组,接受过至少1剂ANV/3TC/TDF(n=381)或EVG/Cobi/FTC/TAF(n=381).在第48周,ANV/3TC/TDF的7名(1.8%)参与者和EVG/Cobi/FTC/TAF的6名(1.6%)参与者的血浆HIV-1RNA滴度为50个拷贝/mL或以上,包括时间窗口内丢失的病毒学数据(Cochran-Mantel-Haenszel方法,估计治疗差异[ETD],0.3%,95%CI-1.6至2.1),建立ANV/3TC/TDF对EVG/Cobi/FTC/TAF的非劣效性。在两组之间,经历至少一次治疗引起的不良事件(AE)的参与者比例相当(97.6%对97.6%)。一小部分参与者因不良事件(0.3%对0.3%)而停用研究药物。严重不良事件发生在11名(2.9%)ANV/3TC/TDF参与者和9名(2.4%)EVG/Cobi/FTC/TAF参与者,分别,在研究者的管辖范围内,没有一项被认为与研究药物有关.在第48周,与使用EVG/Cobi/FTC/TAF的参与者相比,使用ANV/3TC/TDF的参与者的体重增加明显减少(最小二乘均值,1.16对2.05公斤,ETD-0.90kg,95%CI,-1.43至-0.37)。血清脂质从基线的变化也有利于ANV/3TC/TDF超过EVG/Cobi/FTC/TAF。
■在先前基于NNRTI的ARV方案的病毒学抑制PLWH中,切换到ANV/3TC/TDF导致较少体重增加,和改善脂质代谢,同时保持病毒学抑制不劣于EVG/Cobi/FTC/TAF。
■江苏艾达制药&国家“十三五”期间国家国家科技部重大创新药物研发重点项目。
UNASSIGNED: We compared the efficacy and safety profiles of
ainuovirine (ANV), a new-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), with boosted elvitegravir (EVG), both coformulated with two nucleoside reverse transcriptase inhibitors (NRTIs), in people living with HIV-1 (PLWH) who had achieved virological suppression on previous NNRTI-based antiretroviral (ARV) regimen.
UNASSIGNED: This study was a multi-centre, randomised, double-blind, active-controlled, non-inferiority trial recruiting PLWH from 10 clinical centres across China. Main inclusion criteria included age of 18-65 years (inclusive), and stably staying on an ARV regimen combining an NNRTI with a two-drug NRTI backbone for at least 12 months. Eligible participants must have maintained plasma HIV-1 ribonucleic acid (RNA) titre below 50 copies per mL confirmed on two successive tests at an interval of at least one month prior to randomisation. Participants were randomly assigned to receive ANV 150 mg plus lamivudine (3TC) 300 mg, and tenofovir disoproxil fumarate (TDF) 300 mg (ANV/3TC/TDF), or cobicistat (Cobi) 150 mg boosted EVG plus emtricitabine (FTC) 200 mg, and tenofovir alafenamide (TAF) 10 mg. The primary efficacy endpoint was the proportion of participants with HIV-1 RNA titre at 50 copies per mL or above at week 48 using the US Food and Drug Administration snapshot algorithm, with a non-inferiority margin of 4 percentage points at a two-side 95% confidence level. This trial is active, but not recruiting, and is registered with Chinese Clinical Trial Registry (ChiCTR), number ChiCTR2100051605.
UNASSIGNED: Between October 2021 and February 2022, 923 patients were screened for eligibility, among whom 762 participants were randomized and had received at least one dose of ANV/3TC/TDF (n = 381) or EVG/Cobi/FTC/TAF (n = 381). At week 48, 7 (1.8%) participants on ANV/3TC/TDF and 6 (1.6%) participants on EVG/Cobi/FTC/TAF had plasma HIV-1 RNA titre at 50 copies per mL or above, including missing virological data within the time window (the Cochran-Mantel-Haenszel method, estimated treatment difference [ETD], 0.3%, 95% CI -1.6 to 2.1), establishing the non-inferiority of ANV/3TC/TDF to EVG/Cobi/FTC/TAF. The proportions of participants experiencing at least one treatment-emergent adverse events (AEs) were comparable between the two arms (97.6% versus 97.6%). A small proportion of participants discontinued study drug due to AEs (0.3% versus 0.3%). Serious AEs occurred in 11 (2.9%) participants on ANV/3TC/TDF and 9 (2.4%) participants on EVG/Cobi/FTC/TAF, respectively, none of which was considered related to study drug at the jurisdiction of the investigator. At week 48, participants on ANV/3TC/TDF showed a significantly less weight gain from baseline compared to those on EVG/Cobi/FTC/TAF (least square mean, 1.16 versus 2.05 kg, ETD -0.90 kg, 95% CI, -1.43 to -0.37). The changes in serum lipids from baseline also favoured ANV/3TC/TDF over EVG/Cobi/FTC/TAF.
UNASSIGNED: In virologically suppressed PLWH on previous NNRTI-based ARV regimen, switch to ANV/3TC/TDF resulted in less weight gain, and improved lipid metabolism while maintaining virological suppression non-inferior to that to EVG/Cobi/FTC/TAF.
UNASSIGNED: Jiangsu Aidea Pharmaceutical & the National \"Thirteenth Five-year Period\" Major Innovative Drugs Research and Development Key Project of the People\'s Republic of China Ministry of Science and Technology.