Results from the RIVER study, which tested the 'kick and kill' approach, were presented at the International AIDS Conference in Amsterdam earlier today. The study tested therapy combinations to target the HIV reservoir in patients already on antiretroviral therapy (ART). RIVER looked to understand how to achieve a functional cure for HIV.
The results of the study showed no difference in effect between participants in the 'kick and kill' therapy group and the control group (on standard treatment). However, the study establishes a precedent for researchers to test further treatment combinations, and continue the search for an HIV cure.
ART reduces the levels of HIV in the body, by stopping HIV from making copies of itself. For patients treated successfully, this means their viral load becomes undetectable. This does not mean that HIV has gone, just that levels are too low to easily measure. This low level of remaining virus is known as the 'reservoir'. Researchers proposed that a potential cure for HIV would be to target this reservoir.
The RIVER study, which ran from 2015 to 2018 in London and Brighton research sites, tested the 'kick and kill' approach in 60 men recently diagnosed with HIV and who had the virus under control by taking ART. A novel four-drug ART combination was used for the study. Three medicines were given in addition to ART; a drug to 'wake up' the HIV reservoir (the 'kick') was given with two vaccines to stimulate the immune system and train it to destroy HIV (the 'kill'). RIVER featured further novelty, as the study was the first HIV cure study to use a randomised controlled approach.
The researchers found that around half of the participants taking the 'kill and kill' therapy still had similar levels of infected reservoir cells compared to those receiving standard ART.
RIVER Chief Investigator, Professor Sarah Fidler of Imperial College London said: "In the RIVER study, we found that all the separate parts of the kick and kill approach worked as expected and were safe. The vaccine worked on the immune system, the kick drug behaved as we expected it to, and the ART worked in suppressing viral load in the body, but the study has shown that this particular set of treatments together didn't add up to a potential cure for HIV, based on what we've seen so far."
Based on the results of the study, it was not possible to recommend that all the participants start taking the 'kick and kill' drugs.
Having been the first HIV cure trial to use a randomised controlled approach, the authors urge that this approach be repeated in the future. Professor Abdel Babiker of the MRC Clinical Trials Unit at UCL, said: "Although the results are disappointing, they are unambiguous because of the randomisation and completeness of follow up assessments. Because ART is so effective at reducing viral load, without the randomised control group of participants taking ART alone to compare against, we couldn't have been so confident in knowing whether the 'kick and kill' drugs had made any impact. It's important that future HIV cure trials follow this approach and compare their outcomes to an ART-only group."
Participants of the RIVER study showed extraordinary commitment, with all 60 participants attending their primary endpoint study visits.
Damian Kelly, RIVER community advisory board leader and Director of the Patient Advocacy Alliance said: "Everyone involved in RIVER - the participants, the clinic staff who have such a critical role in keeping participants engaged and supported, the doctors, the lab technicians and the scientists - everyone should be proud that they were involved in the first randomised controlled HIV cure trial."