The RIO trial assessed the impact of two long-acting immune therapies known as broadly neutralising antibodies, or bNAbs, compared with placebo, among 68 people living with HIV who stopped taking their antiretroviral medicines.
The trial primary outcome results, announced at the annual Conference on Retroviruses and Opportunistic Infections, showed that three quarters of participants who received the bNAbs were able to control the virus while off their antiretroviral therapy, compared to those who received a placebo over a 20-week period.
While the trial primary findings have not yet been published in an academic journal and are therefore not yet peer reviewed, the RIO project team – a research partnership between the University of Oxford, Imperial College London and Rockefeller University, New York - believes they mark an exciting development.
Professor Sarah Fidler of the Department of Infectious Disease at Imperial College London, and chief investigator of the study, said: ‘This is the first time a long-acting immune-based therapy has shown sustained viral control in multiple participants, allowing them to stop their daily antiretroviral medication for over a year. These results could open new avenues for HIV treatment, bringing us closer to our ultimate goal of achieving a cure.’
Professor Fidler is also the Co-Chair of Imperial's Global Development Hub, which focuses on the most pressing research challenges of our time, including HIV.
Professor John Frater, Professor of Infectious Diseases in NDM’s Experimental Medicine Division and co-lead investigator, said: ‘These bNAbs function in two ways—first, by directly targeting and killing HIV, and second, by stimulating new and stronger immune responses. Those who developed the most robust immune responses maintained viral control for the longest period. This is the first evidence that an immune response can be harnessed to control HIV, potentially paving the way for viral eradication.’
The antibody therapies also had an impact on another element of HIV infection in trial participants.
Current antiretroviral therapy is unable to target latent HIV-infected cells – immune system cells that are infected with HIV but are not actively producing new copies of the virus. These latent cells are known as the so-called ‘reservoir’ of HIV infection - which is why at present there is no cure.
However, co-lead researchers from the Rockefeller University in New York, Professor Michel Nussenzweig, the Zanvil A. Cohn and Ralph M. Steinman Professor and co-director of Immunology for the Stavros Niarchos Foundation Institute for Global Infectious Disease Research, and Professor Marina Caskey, said: ‘The RIO trial has shown that long-acting bNAbs significantly reduced the size of this reservoir, even reaching undetectable levels in some participants. Since eliminating the reservoir is crucial for curing HIV, these findings represent a significant step forward.’
‘These results are the first time that immune-based treatments have kept viral load undetectable without ART for so long. People who respond to bNAbs could have a new option for HIV treatment,’ said Simon Collins, RIO leadership group community representative.
The promising results from the RIO trial suggest that bNAb-based therapies could play a pivotal role in future HIV treatment strategies.
The study participants still in follow-up will continue to be monitored until all remaining protocol defined endpoints are completed - anticipated in 2027.
The RIO study was funded by the Gates Foundation, the National Institutes of Health USA, the National Health Service UK, and the Stavros Niarchos Foundation.
Dr Mike McCune, head of the HIV Frontiers program at the Gates Foundation, echoed the importance of the trial results in the broader search for an HIV cure: ‘The results of the RIO study show that progress is possible in the effort to revolutionize HIV treatment. By demonstrating the promise of bNAbs in durable viral suppression, this study also unlocks critical insights that could help advance the development of safe, effective, and affordable gene-based HIV therapies. This type of cutting-edge research and innovation will be key to finally ending the global threat of HIV.’
This research was supported by funding from the National Institute for Health and Care Research (NIHR) Imperial Biomedical Research Centre (BRC), a translational research partnership between Imperial College London and Imperial College Healthcare NHS Trust, which also supports Imperial Clinical Trials Unit (ICTU) and Imperial Clinical Research Facility (ICRF).