Switch to fixed-dose ainuovirine, lamivudine, and tenofovir DF versus elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in virologically suppressed people living with HIV-1: the 48-week results of the SPRINT trial, a multi-centre, randomised, double-blind, active-controlled, phase 3, non-inferiority trial

IF 7.6 1区 医学 Q1 HEALTH CARE SCIENCES & SERVICES
Fujie Zhang , Hao Wu , Weiping Cai , Ping Ma , Qingxia Zhao , Hongxia Wei , Hongzhou Lu , Hui Wang , Shenghua He , Zhu Chen , Yaokai Chen , Min Wang , Wan Wan , Heliang Fu , Hong Qin
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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. 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引用次数: 0

Abstract

Background

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.

Methods

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.

Findings

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.

Interpretation

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.

Funding

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.

在病毒学抑制的 HIV-1 感染者中改用固定剂量阿奴韦林、拉米夫定和替诺福韦 DF 与艾维特拉韦、科比司他、恩曲他滨和替诺福韦阿afenamide 的对比:SPRINT 试验(一项多中心、随机、双盲、主动对照、第 3 期、非劣效试验)的 48 周结果
背景我们比较了新一代非核苷类逆转录酶抑制剂(NNRTI)艾诺韦林(ANV)与艾维特拉韦(EVG)(均与两种核苷类逆转录酶抑制剂(NRTI)联合配制)对既往接受过基于NNRTI的抗逆转录病毒(ARV)治疗并获得病毒学抑制的HIV-1感染者(PLWH)的疗效和安全性。方法该研究是一项多中心、随机、双盲、主动对照、非劣效试验,招募了来自中国 10 个临床中心的 PLWH。主要纳入标准包括年龄在18-65岁(含)之间,稳定服用NNRTI与NRTI双药联合的抗逆转录病毒疗法至少12个月。符合条件的参与者必须在随机分配前至少间隔一个月连续两次检测确认血浆 HIV-1 核糖核酸 (RNA) 滴度低于 50 拷贝/毫升。参试者被随机分配接受ANV 150毫克加拉米夫定(3TC)300毫克和富马酸替诺福韦二吡呋酯(TDF)300毫克(ANV/3TC/TDF),或科比司他(Cobi)150毫克增强型EVG加恩曲他滨(FTC)200毫克和替诺福韦-阿拉非酰胺(TAF)10毫克。主要疗效终点是根据美国食品药品管理局的快照算法,第48周时HIV-1 RNA滴度达到或超过50拷贝/毫升的参与者比例,在双侧95%置信水平下,非劣效边际为4个百分点。研究结果在2021年10月至2022年2月期间,共筛选出923名符合条件的患者,其中762名参与者被随机分组,并至少接受过一次ANV/3TC/TDF(n = 381)或EVG/Cobi/FTC/TAF(n = 381)治疗。第48周时,7名(1.8%)接受ANV/3TC/TDF治疗的参与者和6名(1.6%)接受EVG/Cobi/FTC/TAF治疗的参与者的血浆HIV-1 RNA滴度达到或超过50拷贝/毫升,包括时间窗内缺失的病毒学数据(Cochran-Mantel-Haenszel法,估计治疗差异[ETD],0.3%,95% CI-1.6至2.1),从而确定了ANV/3TC/TDF与EVG/Cobi/FTC/TAF的非劣效性。两组患者中至少出现一次治疗突发不良事件(AEs)的比例相当(97.6% 对 97.6%)。一小部分参与者因不良反应而停药(0.3% 对 0.3%)。分别有11名(2.9%)服用ANV/3TC/TDF的参与者和9名(2.4%)服用EVG/Cobi/FTC/TAF的参与者发生严重AE,经研究者判断,这些AE均与研究药物无关。第48周时,与服用EVG/Cobi/FTC/TAF的参与者相比,服用ANV/3TC/TDF的参与者体重从基线增加的幅度明显较小(最小平方均值为1.16对2.05千克,ETD为-0.90千克,95% CI为-1.43对-0.37)。在病毒学抑制的PLWH中,以前使用的是基于NNRTI的抗逆转录病毒药物方案,改用ANV/3TC/TDF后体重增加较少,血脂代谢得到改善,同时病毒学抑制效果不劣于EVG/Cobi/FTC/TAF。基金资助江苏爱迪药业股份有限公司;国家科技部 "十三五 "重大创新药物研发重点专项。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
The Lancet Regional Health: Western Pacific
The Lancet Regional Health: Western Pacific Medicine-Pediatrics, Perinatology and Child Health
CiteScore
8.80
自引率
2.80%
发文量
305
审稿时长
11 weeks
期刊介绍: The Lancet Regional Health – Western Pacific, a gold open access journal, is an integral part of The Lancet's global initiative advocating for healthcare quality and access worldwide. It aims to advance clinical practice and health policy in the Western Pacific region, contributing to enhanced health outcomes. The journal publishes high-quality original research shedding light on clinical practice and health policy in the region. It also includes reviews, commentaries, and opinion pieces covering diverse regional health topics, such as infectious diseases, non-communicable diseases, child and adolescent health, maternal and reproductive health, aging health, mental health, the health workforce and systems, and health policy.
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