The RIO clinical trial will test whether a new type of therapy can keep HIV under control without daily antiretroviral treatment (ART) tablets.
The novel therapy uses a combination of two experimental antibodies (called broadly neutralising monoclonal antibodies, or bNAbs) which have been designed by scientists at the Rockefeller University to target multiple strains of HIV.
The RIO study, jointly led by Imperial College London, the University of Oxford and the Rockefeller University, will use viral load blood tests to measure how long HIV can be controlled using bNAbs. To do this, trial participants will be randomised to receive either a bNAb injection or a placebo before stopping their ART tablets.
Currently, people living with HIV take a daily tablet of ART, which keeps the virus at undetectable levels, making it untransmittable. RIO is looking at whether this new approach might allow people living with HIV to have periods of time where they do not need to take daily ART. Participants will be asked to restart their ART when the virus becomes detectable in a blood test (‘viral rebound’).
The study will also test the mechanisms by which these experimental antibodies work. Scientists will measure whether the immune system is boosted by the bNAbs, resulting in continued control of HIV, even after the antibodies have cleared.
A new approach to HIV treatment
RIO Chief Investigator, Professor Sarah Fidler of Imperial’s Department of Infectious Disease, said: “We are really pleased to open the RIO trial, the first randomised trial of its kind, designed to carefully measure the effects of the new treatments to control HIV after stopping ART.”
Professor John Frater, University of Oxford, who is co-lead of the study said: “The RIO trial is the first major study to test an exciting new class of treatments for HIV, with potential to allow people to stop taking tablets and even to confer a form of remission from infection – a crucial pathway in the search for an HIV cure.”
“This study provides a unique opportunity to evaluate the effects of antibodies on the participants’ own immune responses against HIV. The participants in this study are people living with HIV who started treatment early after infection who we think have stronger immune responses to fight off the virus when ART is discontinued”, said Marina Caskey, Co-Investigator at the Rockefeller University.
Following initial delays to the trial due to the COVID-19 pandemic, RIO is now open to recruitment with extra precautions to ensure the safety of the participants. Individuals joining the trial will be tested for COVID-19 and will have received their COVID-19 vaccination.
The study aims to recruit 72 participants and will run until July 2024.
Seven centres are participating in RIO:
- St Mary’s Hospital, London, Imperial College Healthcare NHS Trust,
- Royal Free Hospital, Royal Free London NHS Foundation Trust,
- Mortimer Market Centre, Central and Northwest London NHS Foundation Trust,
- Chelsea and Westminster Hospital, Chelsea and Westminster Hospital NHS Foundation Trust,
- St Thomas’ Hospital, London, Guy’s and St Thomas’ NHS Foundation Trust,
- The Royal London Hospital, Barts’ Health NHS Trust,
- The Royal Sussex County Hospital, Brighton and Sussex University Hospitals NHS Trust.
The University of Oxford and the Rockefeller University in New York will both study samples from the participants to work out how the new antibodies are working, and how the immune system is responding.
The RIO trial is funded by the Bill & Melinda Gates Foundation and sponsored by Imperial College London. The trial is jointly coordinated by Imperial College London, the University of Oxford and the Rockefeller University.
RIO is part of the CHERUB research collaboration. CHERUB (‘Collaborative HIV Eradication of Reservoirs UK BRC’) is a UK network of internationally recognised doctors and investigators from the NIHR Biomedical Research Centres in London, Oxford and Cambridge, working together with patients and community representatives to find a cure for HIV infection.