RIVER
Research In Viral Eradication of HIV Reservoirs
The RIVER study tried to understand how to achieve a functional cure of HIV using the ‘kick and kill’ approach to reduce the size of the HIV reservoir.
What was this study about?
Antiretroviral Therapy (ART) reduces the levels of HIV in the body, by stopping HIV from making copies of itself (replicating). We can measure the amount of HIV in the body using a test called viral load. For most people, within a few months of starting ART their viral load becomes undetectable. This does not mean that HIV has gone, just that levels are too low to easily measure. Importantly, having an undetectable viral load is associated with remaining healthy and well for many years.
In most positive patients, the only way to have an undetectable viral load is to take ART every day. If ART is stopped, HIV will become detectable again. The reason for this is that ART only works against HIV that is in awake and active immune cells. However, most immune cells are resting or ‘asleep’ and some of these cells contain HIV. These cells, which are hidden from ART, are called the HIV reservoir. This reservoir is the reason that HIV comes back again if ART is stopped. If ART is stopped the HIV within the sleeping cells will wake up, begin replicating and the person’s viral load will quickly increase. The reservoir is also the main reason why we can’t cure people of HIV even with effective ART.
The RIVER study tested a new way to reduce the size of the HIV reservoir, using an approach called “kick and kill”. Vorinostat, a HDAC inhibitor, is the “kick” and the boosted immune response is the “kill”.
There are four steps in this approach:
1. ART is used to make sure HIV is undetectable.
2. Two vaccines are then used to train the immune system to recognise cells that will be activated.
3. Vorinostat is used to wake and activate the sleeping HIV containing cells.
4. The immune system, boosted by the vaccines, attacks and kills the newly activated cells.
The aim of this approach and the RIVER study is to reduce the size of this HIV reservoir. Ultimately, this might mean that people could stop their ART and still remain undetectable.
Please watch this short animation for further information regarding the RIVER study:
The results of RIVER are published in The Lancet.
Open the RIVER results summary for trial participants.
What difference did this study make?
RIVER found that all the separate parts of the kick and kill approach worked as expected and were safe. But together they did not add up to a potential cure for HIV. The trial found no difference between participants in the 'kick and kill' therapy group and the control group on standard ART.
Based on the results of the study, it was not possible to recommend that all the participants start taking the 'kick and kill' drugs.
However, the study established a precedent for researchers to test further treatment combinations, and continue the search for an HIV cure.
All participants were followed for a further five years to report on any further safety events, this follow-up finished at the end of 2023 with no major safety concerns identified.
Type of study
Randomised trial
Contact details
Who funded the study?
RIVER was funded by the UK Medical Research Council and industry partners.
When did it take place?
Recruitment to the RIVER study started in December 2015 and closed in February 2017. Follow-up ended in 2023.
Where did it take place?
RIVER took place in six sites in the UK:
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Royal Sussex County Hospital, Brighton
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Mortimer Market Centre, London
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St Mary's Hospital, London
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Chelsea & Westminster Hospital, London
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Royal Free Hospital, London
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St Thomas's Hospital, London
Who was included?
To join RIVER, participants must have been recently infected with HIV. Participants were randomly allocated to either receive ART or receive the vaccines plus vorinostat, in addition to ART.