First major study of new HIV therapy opens to recruitment
by Geneviéve Timmins
01 July 2021
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.”
"The new treatments might let some people living with HIV stop ART for six months or longer - and still keep viral load undetectable," adds Simon Collins, an advocate at HIV i-Base.
“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.
Universal ‘Test and Treat’ for HIV cost-effective in high prevalence regions.
Rolling out home-based testing and universal treatment for HIV is cost-effective and can cut the incidence of cases in high-prevalence communities.
These are the findings of a major HIV-prevention study involving more than one million people in Zambia and South Africa, published in The Lancet Global Health.
IAS bids sad farewell to Timothy Ray Brown, the “Berlin patient”
30 June 2020
It is with a profoundly heavy heart that IAS – the International AIDS Society – today mourns the passing of Timothy Ray Brown, the first person to be cured of HIV.
Known as the “Berlin Patient”, Mr Brown was cured of HIV in 2008 after undergoing a complex stem cell transplant for acute leukaemia.
For the past six months, Mr Brown had been living with a recurrence of the leukaemia that had entered his spine and brain. He had remained HIV free.
“On behalf of all its members and the Governing Council, the IAS sends its condolences to Timothy’s partner, Tim, and his family and friends,” Adeeba Kamarulzaman, President of the IAS and Professor of Medicine and Infectious Diseases at the University of Malaya, said.
“We owe Timothy and his doctor, Gero Hütter, a great deal of gratitude for opening the door for scientists to explore the concept that a cure for HIV is possible.
Mr Brown, living with HIV and with acute myeloid leukaemia, received a bone marrow transplant in Berlin, Germany, in 2007. The donor was naturally resistant to HIV infection because of a mutation in the CCR5 gene, a critical protein required by HIV to enter and infect cells.
Mr Brown stopped antiretroviral therapy (ART) very soon after the transplant and he remained free of any detectable virus. In other words, he was cured. His experience suggested that HIV might one day be curable. This fuelled a range of efforts by researchers and institutions focusing on HIV cure research.
One such effort is the IAS Towards an HIV Cure initiative, established in 2011 to promote and facilitate the search for a safe and affordable cure that can be scaled up. Professor Sharon Lewin, President-Elect of the IAS and Director of the Doherty Institute in Melbourne, Australia, co-chairs this IAS initiative with Mark Dybul, a former Executive Director of the Global Fund to Fight AIDS, Tuberculosis and Malaria and US Global AIDS Coordinator. Steven Deeks, Professor of Medicine in Residence at the University of California is the Chief Scientific Advisor of the Towards an HIV Cure Advisory Board.
A full decade after Timothy Brown’s cure, Adam Castillejo, who had also been living with HIV, reportedly remained in HIV remission off ART, 19 months after receiving a bone marrow transplant for Hodgkin’s lymphoma from a CCR5-negative donor. Now known as the “London Patient”, he remains in remission and is widely considered to be the second man cured of HIV.
“Although the cases of Timothy and Adam are not a viable large-scale strategy for a cure, they do represent a critical moment in the search for an HIV cure,” Sharon Lewin said.
“Timothy was a champion and advocate for keeping an HIV cure on the political and scientific agenda. It is the hope of the scientific community that one day we can honour his legacy with a safe, cost-effective and widely accessible strategy to achieve HIV remission and cure using gene editing or techniques that boost immune control.”
In late August, it was reported that Loreen Willenberg, a woman who had been living with HIV since 1992, had no traces of intact HIV despite not using ART. She may be the first person cured of HIV without undergoing a risky bone marrow transplant. Researchers believe that she may be an “extreme elite controller”, where only fragments of HIV remain and these fragments are unable to replicate.
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