ART联合踢杀法治疗HIV新近感染者的疗效并不优于单独ART
2020-03-05   阅读:483   来源:柳叶刀

英国牛津大学John Frater联合伦敦帝国理工大学Sarah Fidler课题组近日取得一项新成果。他们的最新研究比较了抗逆转录病毒疗法单独与联合踢杀法治疗新近感染艾滋病患者的效果。2020年2月18日出版的《柳叶刀》发表了这项成果。

抗逆转录病毒疗法(ART)不能治愈HIV感染,因为潜在感染细胞持久存在。为了彻底治愈HIV,有人研究了迫使HIV从感染细胞中转录,使其易被杀死的方案(踢杀方案)。

为了探讨踢杀方案的效果,2015年6月14日至2017年7月11日,研究组在英国的6个临床医疗点进行了一项临床2期、开放标签、多中心、随机对照研究,招募了60名18至60岁在过去6个月内确诊HIV,并在确诊后1个月内开始ART的患者。

将其随机分组,其中30例仅接受ART,30例接受ART+组蛋白去乙酰化酶伏立诺他(踢)+复制缺陷型病毒载体T细胞诱导疫苗(杀)(ART+V+V)方案。

治疗16和18周后,仅ART组中每106个CD4+ T细胞的平均总HIV DNA为3.02 log10 拷贝,ART+V+V组为3.06 log10 拷贝,组间差异不显著。未发生治疗相关的严重不良事件。

总之,与单独ART相比,这种踢杀方案治疗HIV并未明显获益。

附:英文原文

Title: Antiretroviral therapy alone versus antiretroviral therapy with a kick and kill approach, on measures of the HIV reservoir in participants with recent HIV infection (the RIVER trial): a phase 2, randomised trial

Author: Sarah Fidler, Wolfgang Sthr, Matt Pace, Lucy Dorrell, Andrew Lever, Sarah Pett, Sabine Kinloch-de Loes, Julie Fox, Amanda Clarke, Mark Nelson, John Thornhill, Maryam Khan, Axel Fun, Mikaila Bandara, Damian Kelly, Jakub Kopycinski, Tomá Hanke, Hongbing Yang, Rachel Bennett, Margaret Johnson, Bonnie Howell, Richard Barnard, Guoxin Wu, Steve Kaye, Mark Wills, Abdel Babiker, John Frater, Eric Sandstrm, Janet Darbyshire, Frank Post, Christopher Conlon, Jane Anderson, Mala Maini, Timothy Peto, Peter Sasieni, Veronica Miller, Ian Weller, Sarah Fidler, John Frater, Abdel Babiker, Wolfgang Sthr, Sarah Pett, Lucy Dorrell, Matthew Pace, Natalia Olejniczak, Helen Brown, Nicola Robinson, Jakub Kopycinski, Hongbing Yang, Tomá Hanke, Alison Crook, Steven Kaye, Myra McClure, Otto Erlwein, Andrew Lovell, Maryam Khan, Michelle Gabrielle, Rachel Bennett, Aminata Sy, Adam Gregory, Fleur Hudson, Charlotte Russell, Gemma Wood, Hanna Box, Cherry Kingsley, Katie Topping, Andrew Lever, Mark Wills, Axel Fun, Mikaila Bandara, Damian Kelly, Simon Collins, Alex Markham, Mary Rauchenberger, Yinka Sowunmi, Shaadi Shidfar, Dominic Hague, Mark Nelson, Maddalena Cerrone, Nadia Castrillo Martinez, Tristan Barber, Alexandra Schoolmeesters, Christine Weaver, Orla Thunder, Jane Rowlands, Christopher Higgs, Serge Fedele, Margherita Bracchi, Lervina Thomas, Peter Bourke, Nneka Nwokolo, Gaynor Lawrenson, Marzia Fiorino, Hinal Lukha, Sabine Kinloch-de Loes, Margaret Johnson, Alice Nightingale, Nnenna Ngwu, Patrick Byrne, Zoe Cuthbertson, Martin Jones, Tina Fernandez, Amanda Clarke, Martin Fisher, Rebecca Gleig

Issue&Volume: February 18, 2020

Abstract: BackgroundAntiretroviral therapy (ART) cannot cure HIV infection because of a persistent reservoir of latently infected cells. Approaches that force HIV transcription from these cells, making them susceptible to killing—termed kick and kill regimens—have been explored as a strategy towards an HIV cure. RIVER is the first randomised trial to determine the effect of ART-only versus ART plus kick and kill on markers of the HIV reservoir.MethodsThis phase 2, open-label, multicentre, randomised, controlled trial was undertaken at six clinical sites in the UK. Patients aged 18–60 years who were confirmed as HIV-positive within a maximum of the past 6 months and started ART within 1 month from confirmed diagnosis were randomly assigned by a computer generated randomisation list to receive ART-only (control) or ART plus the histone deacetylase inhibitor vorinostat (the kick) and replication-deficient viral vector T-cell inducing vaccines encoding conserved HIV sequences ChAdV63. HIVconsv-prime and MVA.HIVconsv-boost (the kill; ART+V+V; intervention). The primary endpoint was total HIV DNA isolated from peripheral blood CD4 + T-cells at weeks 16 and 18 after randomisation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02336074.FindingsBetween June 14, 2015 and Jul 11, 2017, 60 men with HIV were randomly assigned to receive either an ART-only (n=30) or an ART+V+V (n=30) regimen; all 60 participants completed the study, with no loss-to-follow-up. Mean total HIV DNA at weeks 16 and 18 after randomisation was 3·02 log 10 copies HIV DNA per 10 6 CD4 + T-cells in the ART-only group versus 3·06 log 10 copies HIV DNA per 10 6 CD4 + T-cells in ART+V+V group, with no statistically significant difference between the two groups (mean difference of 0·04 log 10 copies HIV DNA per 10 6 CD4 + T-cells [95% CI 0·03 to 0·11; p=0·26]). There were no intervention-related serious adverse events.InterpretationThis kick and kill approach conferred no significant benefit compared with ART alone on measures of the HIV reservoir. Although this does not disprove the efficacy kick and kill strategy, for future trials enhancement of both kick and kill agents will be required.

DOI: 10.1016/S0140-6736(19)32990-3

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