Researchers report first results of randomized trials of the "kick and kill" approach to treat HIV

July 24, 2018

Researchers reported the results of the first randomized clinical trial to test a new strategy involving waking up and then killing the "sleeping" HIV that lurks in the body using an experimental approach called "Led by Imperial College London, Oxford University, the CRM Clinical Trials Unit at UCL and the University of Cambridge, the RIVER study aimed to improve care to eradicate HIV from the body, which

Although investigators found no difference in effect between participants who received active therapy "kick and kill" and those who received a standard treatment, they claim that the trial opens the way to treatment. to test different combinations of HIV therapies that persist in patients receiving antiretroviral therapy (ART). The trial demonstrates how researchers are looking beyond current therapies that, although they are revolutionizing the lives of people living with HIV, do not heal and need to be taken for life

L & # 39; RIVER study, which took place from 2015 to 2018 in London and Brighton tested the "kick and kill" approach in 60 men recently diagnosed with HIV and who have mastered the virus while taking antiretrovirals. Despite undetectable levels of HIV in the blood, patients on antiretroviral therapy are not cured. If they stop taking antiretroviral therapy, the virus comes back from hiding places in the body called "reservoirs". This has led researchers to suggest that a cure for HIV could be targeting these reservoirs, forcing HIV to hide and then kill it.

To test this idea, RIVER used two drugs in addition to ART standard treatment. First, two vaccines to train the body's immune system to recognize and destroy HIV, and second, a drug called vorinostat (also used to manage cancer) that would "wake up" the cells in the reservoir where HIV is hiding and force the virus to reveal itself and deal with the immune system. This approach to HIV treatment is called "kick and kill" – the kick is delivered by vorinostat, and death comes from the body's immune system killer cells that have been driven by the vaccines .

Claiming success in the RIVER proof-of-concept trial, the researchers said those who receive the shot and kill the drugs should experience a significant drop in HIV levels in the reservoir cells, called CD4 T cells.

However, when the results were unveiled to researchers In April 2018, they found that half of the study participants receiving the kick and killing drugs in addition to TAR had similar levels of cells infected compared to those receiving only standard antiretroviral therapy.

during a session "Late Breaker" at the annual meeting of the International AIDS Society in Amsterdam, Netherlands (AIDS 2018). The results of the study will be submitted for publication in a peer-reviewed journal.

The chief investigator of RIVER, Professor Sarah Fidler of Imperial College London said:

"In the RIVER study, we found that all parts separated the vaccine worked on the immune system, the drug worked as expected, and antiretroviral therapy helped to suppress the viral load in the body, but the study showed that after what we saw up to # Here, the combination of treatments was not a potential cure for HIV. "

" For those who have access to it, antiretroviral therapy is incredibly successful, but people need to think about it. Other durable alternatives, and a cure or at least a form of remission is a key goal. "Finding a cure for HIV means orchestrating many things. We need to generate new ideas and turn them into trials that will yield significant results, we need to agree that the research tests will tell us whether things are working or not, we need to watch very carefully the participants in the study and Most importantly, we must make sure any test intervention is safe. RIVER has achieved all these things but unfortunately not evidence of a possible cure for HIV. "

Based on the findings, the study's doctors told participants that they can not recommend all participants to receive the kick and kill the drugs." ART and that the trial no evidence was found to recommend all participants to safely stop their antiretroviral therapy.

In anticipation of possible next steps, the principal investigator and principal investigator of the RIVER, the Professor John Frater of Oxford University said:

"We have to think about why we have not seen an effect. The important thing to realize is that despite these disappointing results, this does not mean that the basis of the approach is wrong. This is the first ever randomized study on the concept of "kick and kill" in humans and the field must now work together to explore how better and more effective agents can impact the HIV reservoir. while remaining safe.

It is possible that the drug combinations we used were not entirely correct, but for this first study, we did not want to compromise safety by using stronger agents that could work better but which could cause toxicity in the participants. It was not powerful enough to wake up as much HIV as necessary for the newly formed immune system to recognize it. In addition, it is possible that a different type of immune response to the one we are inducing is needed to target the reservoir of HIV. these possibilities must be discussed and taken into account to guide our next action in the search for a cure for HIV. "

The vaccines used in RIVER, known as ChAdV63.HIVconsv and MVA.HIVconsv, were very effective in inducing HIV-specific immunodeficiencies, responses in the active group.Tracking research could consist of giving more Support for this vaccination with a different drug or to possibly use the "next generation" of these vaccines that are currently being tested in other studies.

RIVER was headed by "CHERUB", British collaboration of five Universities pooling their expertise to develop a cure for HIV.CHERUB is supported by the National Institute for Health Research and brings together researchers on HIV at Imperial College London, in London. University of Oxford, University of Cambridge, UCL Medical Research Council Clinical Trials Unit and King's College London RIVER was funded by Medical Rese Arch Council, UK and industrial partners, MSD and GSK.

RIVER was the first HIV treatment study to use a randomized controlled approach, and the authors recommend that this be repeated. . Professor Abdel Babiker of the CRM Clinical Trials Unit at UCL said:

"Although the results are disappointing, they are unambiguous because of the randomization and the lack of data. Completeness of Follow-up Assessments We could not be as sure whether HIV cure trials followed this approach and compared their results to antiretroviral therapy "group alone."

In its three years, RIVER benefited from an exceptional commitment from its 60 participants.Participation in the study visits of the main criterion was 100% and no participant was lost from the study According to the experience of doctors and researchers, this has been extraordinary and demonstrates new levels of participant engagement.

"They are absent from work, they come for many visits and of tests, and they form an unbelievable group people, "said Professor Fidler. "They're not just volunteers, they're supportive advocates for support, and they're pushing us further, helping to define where this research can go next, and they are the true pioneers of new treatments."

trial participant said:

"You may have hope, but you must be realistic when you participate in a lawsuit." The results of the previous tests, the way RIVER was designed and the people who support it So, the first results are disappointing because everyone would have liked to see a difference between the control and the active groups. the movement is, but we can not restrain ourselves now in the search for a functional remedy. "

" It is remarkable that no one left the trial, he had an outstanding commitment from the participants because people want to see an HIV cure occur. can see that being involved is the w Damian Kelly, head of the RIVER Community Advisory Board and director of the Patient Advocacy Alliance, said:

"The Cost of HIV Treatment Worldwide and New Rates of HIV" Worldwide infection means that we "Everyone involved in RIVER – the participants, the clinic staff who have such an important role in keeping the participants involved and supported, the doctors, the lab technicians and the scientists – everyone should be proud to have participated in the first randomized controlled trial on HIV treatment. "

" I am confident that not an ounce of effort in the RIVER trial will be wasted the results will help guide and inform the design of future trials and bring us closer to the goal of healing. "