Although the majority of people living with HIV make an antibody response to the virus, these are frequently ineffective and fail to neutralise the virus (i.e. are ‘non-neutralising’), partly due to the development of immune escape mutations in the HIV env gene. High titres of broadly neutralising antibodies (bNAbs) – some of which can neutralise up to 90% of circulating strains – are only made by a small percentage of people and take several years to develop. Until recently bNAbs could not be produced ex vivo to adequate levels using standard immunisation strategies. However, the rise of single cell cloning techniques has revolutionised the field and high titres of bNAbs can now be produced. Further advances have come with the development of LS strains that have much longer half-lives and the potential to further extend the period of virological suppression in the absence of ART.

Over the last few years, bNAbs have entered the clinical arena, initially through proof of concept studies in animal models, followed by dosing and safety studies in humans and then efficacy studies.

The RIO study aims to enrol 72 individuals across multiple UK collaborating clinical centres, and is designed to test the hypothesis that for individuals who commenced antiretroviral therapy (ART) in primary HIV infection (PHI), a combination of the two long-acting broadly neutralising antibodies, 3BNC117-LS and 10-1074-LS, will induce a period of virological remission when ART is stopped compared with participants who received ART plus placebo.

The combination of 3BNC117 and 10-1074 has been tested in humans in a single-arm proof of principle study that suggested that this combination can impose full, sustained viral suppression in the absence of ART. This finding now needs to be investigated using dual long-acting versions of the antibodies in a randomised clinical trial powered to answer the question of whether these bNAbs are effective at controlling HIV replication in the absence of ART.

The results from this trial will demonstrate whether or not the combination of two long-acting (LS) broadly neutralising antibodies, 3BNC117-LS and 10-1074-LS, will prevent HIV viral rebound after stopping antiretroviral therapy for an extended period of time.

The trial – with samples taken during the different permutations of the intervention – will also allow insights into and detailed analysis of adaptive and innate immune responses and the virological correlates of HIV remission off antiretroviral therapy.

Summary of the RIO Study design:

You can read more about the study on the trial website.

Main Funding Body