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.

AIDS Vaccines / administration & dosage Adult Anti-Retroviral Agents / therapeutic use DNA, Viral / analysis Disease Reservoirs HIV Infections / drug therapy Histone Deacetylase Inhibitors / administration & dosage Humans Male Transcription, Genetic / drug effects Treatment Outcome Vorinostat / administration & dosage

Journal

Lancet (London, England)

ISSN: 1474-547X

Titre abrégé: Lancet

Pays: England

ID NLM: 2985213R

Informations de publication

Date de publication:
14 03 2020

Historique:

received: 15 08 2019

revised: 25 10 2019

accepted: 15 11 2019

pubmed: 23 2 2020

medline: 27 3 2020

entrez: 23 2 2020

Statut: ppublish

Résumé

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. 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 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 log 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. Medical Research Council (MR/L00528X/1).

Sections du résumé

BACKGROUND

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

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 log

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.

FUNDING

Medical Research Council (MR/L00528X/1).

Identifiants

DOI: 10.1016/S0140-6736(19)32990-3 PMID: 32085823

pubmed: 32085823

pii: S0140-6736(19)32990-3

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

pii:

doi:

Substances chimiques

AIDS Vaccines 0

Anti-Retroviral Agents 0

DNA, Viral 0

Histone Deacetylase Inhibitors 0

Vorinostat 58IFB293JI

Banques de données

ClinicalTrials.gov

['NCT02336074']

Types de publication

Clinical Trial, Phase II Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng