| 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 |
| Authors: |
Fidler, Sarah; Stöhr, Wolfgang; Pace, Matt; Dorrell, Lucy; Lever, Andrew; Pett, Sarah; Kinloch-de Loes, Sabine; Fox, Julie; Clarke, Amanda; Nelson, Mark; Thornhill, John; Khan, Maryam; Fun, Axel; Bandara, Mikaila; Kelly, Damian; Kopycinski, Jakub; Hanke, Tomáš; Yang, Hongbing; Bennett, Rachel; Johnson, Margaret; Howell, Bonnie; Barnard, Richard; Wu, Guoxin; Kaye, Steve; Wills, Mark; Babiker, Abdel; Frater, John; Sandström, Eric; Darbyshire, Janet; Post, Frank; Conlon, Christopher; Anderson, Jane; Maini, Mala; Peto, Timothy; Sasieni, Peter; Miller, Veronica; Weller, Ian; Pace, Matthew; Olejniczak, Natalia; Brown, Helen; Robinson, Nicola; Crook, Alison; Kaye, Steven; McClure, Myra; Erlwein, Otto; Lovell, Andrew; Gabrielle, Michelle; Sy, Aminata; Gregory, Adam; Hudson, Fleur; Russell, Charlotte; Wood, Gemma; Box, Hanna; Kingsley, Cherry; Topping, Katie; Collins, Simon; Markham, Alex; Rauchenberger, Mary; Sowunmi, Yinka; Shidfar, Shaadi; Hague, Dominic; Cerrone, Maddalena; Castrillo Martinez, Nadia; Barber, Tristan; Schoolmeesters, Alexandra; Weaver, Christine; Thunder, Orla; Rowlands, Jane; Higgs, Christopher; Fedele, Serge; Bracchi, Margherita; Thomas, Lervina; Bourke, Peter; Nwokolo, Nneka; Lawrenson, Gaynor; Fiorino, Marzia; Lukha, Hinal; Nightingale, Alice; Ngwu, Nnenna; Byrne, Patrick; Cuthbertson, Zoe; Jones, Martin; Fernandez, Tina; Fisher, Martin; Gleig, Rebecca; Trevitt, Vittorio; Fitzpatrick, Colin; Adams, Tanya; Finnerty, Fiounnuala; Lewis, Heather; Kuldanek, Kristin; Lwanga, Julianne; Uzu, Hiromi; Lee, Ming; Merle, Simon; O'Rourke, Patrick; Jendrulek, Isabel; ZarkoFlynn, Taras; Taylor, Mark; Tiraboschi, Juan Manuel; Murray, Tammy |
| Publisher Information: |
Lancet Publishing Group |
| Publication Year: |
2020 |
| Collection: |
University of Glasgow: Enlighten - Publications |
| Description: |
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 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 log10 copies HIV DNA per 106 CD4+ T-cells in the ART-only group versus 3·06 log10 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 log10 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 ... |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
Fidler, S. et al. (2020) 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. Lancet , 395(10227), pp. 888-898. (doi:10.1016/S0140-6736(19)32990-3 ) (PMID:32085823) |
| Availability: |
https://eprints.gla.ac.uk/210667/ |
| Accession Number: |
edsbas.73275DF6 |
| Database: |
BASE |