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

被引：103

作者：

Fidler, Sarah ^{[1
,2
]}

Stohr, Wolfgang ^{[3
]}

Pace, Matt ^{[4
,5
]}

Dorrell, Lucy ^{[4
,6
]}

Lever, Andrew ^{[7
,8
]}

Pett, Sarah ^{[3
,9
,10
]}

Kinloch-de Loes, Sabine ^{[11
,13
]}

Fox, Julie ^{[14
,15
]}

Clarke, Amanda ^{[16
,17
,18
]}

Nelson, Mark ^{[19
]}

Thornhill, John ^{[1
,2
]}

Khan, Maryam ^{[1
,2
]}

Fun, Axel ^{[20
]}

Bandara, Mikaila ^{[21
]}

Kelly, Damian ^{[22
]}

Kopycinski, Jakub ^{[4
,6
]}

Hanke, Tomas ^{[4
,23
]}

Yang, Hongbing ^{[4
,6
]}

Bennett, Rachel ^{[3
]}

Johnson, Margaret ^{[12
]}

Howell, Bonnie ^{[24
]}

Barnard, Richard ^{[25
]}

Wu, Guoxin ^{[24
]}

Kaye, Steve ^{[1
]}

Wills, Mark ^{[20
]}

Babiker, Abdel ^{[3
]}

Frater, John ^{[4
,6
]}

机构：

[1] Imperial Coll London, Dept Infect Dis, London, England

[2] NIHR Imperial Biomed Res Ctr, London, England

[3] UCL, Med Res Council Clin Trials Unit, London, England

[4] Univ Oxford, Nuffield Dept Med, Oxford, England

[5] Oxford Martin Sch, Nuffield Dept Med, Oxford, England

[6] Oxford NIHR Biomed Res Ctr, Nuffield Dept Med, Oxford, England

[7] Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge, England

[8] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore, Singapore

[9] Univ Coll London, Inst Global Hlth, London, Singapore

[10] Mortimer Market Ctr, London, England

[11] Royal Free Hosp, Dept Infect & Immun, London, England

[12] Royal Free Hosp, Dept HIV Med, London, England

[13] UCL, London, England

[14] Guys & St Thomas NHS Trust, Dept Genitourinary Med & Infect Dis, London, England

[15] Kings Coll London, NIHR Biomed Res Ctr, Dept Genitourinary Med & Infect Dis, London, England

[16] Elton John Ctr, Brighton, E Sussex, England

[17] Sussex Univ Hosp, Dept HIV & Sexual Hlth, Brighton, E Sussex, England

[18] Univ Sussex, Brighton & Sussex Med Sch, Brighton, E Sussex, England

[19] Imperial Coll London London, Chelsea & Westminster Hosp, Dept HIV Med, London, England

[20] Univ Cambridge, Dept Med, Cambridge, England

[21] Univ Cambridge, Cambridge, England

[22] Patient Advocacy Alliance, Manchester, Lancs, England

[23] Kumamoto Univ, Int Res Ctr Med Sci, Kumamoto, Japan

[24] Merck & Co Inc, Dept Infect Dis & Vaccines, West Point, PA USA

[25] Merck & Co Inc, Global Regulatory Affairs & Clin Safety, N Wales, PA USA

来源：

LANCET | 2020年 / 395卷 / 10227期

基金：

英国医学研究理事会;

关键词：

LATENCY-REVERSING AGENTS; VIRAL LOAD; DNA; REACTIVATION; INHIBITOR; CAPACITY; PREDICTS; SIZE;

D O I：

10.1016/S0140-6736(19)32990-3

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Background Antiretroviral 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. Methods This 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. Findings Between June 14, 2015 and July 11, 2017, 60 men with HIV were randomly assigned to receive either an ARTonly (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 106 CD4+ T-cells in the ART-only group versus 3.06 log 10 copies HIV DNA per 106 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 106 CD4+ T-cells [95% CI -0.03 to 0.11; p=0.26]). There were no intervention-related serious adverse events. Interpretation This 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. Copyright (C) 2020 Elsevier Ltd. All rights reserved.

引用

页码：888 / 898

页数：11

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