Researchers have reported the results of the first randomized clinical trial to test a novel strategy involving waking up and then killing the 'sleeping' HIV that is hiding in the body using an experimental approach known as 'kick and kill'.
The RIVER study aimed to improve on current care by eradicating HIV from the body, which would represent a major step forward in the search for a cure. Although investigators found no difference in effect between those participants who received the active 'kick and kill' therapy and those who had standard treatment, they say the trial paves the way for testing different combinations of therapies to tackle the HIV that persists in patients who receive antiretroviral treatment (ART).
'Kick and kill' Approach
RIVER used two medicines on top of the standard ART treatment. First, two vaccines to coach the body's immune system to recognize and destroy HIV, and second, a drug called vorinostat that would 'wake up' the reservoir cells that HIV is hiding in and force the virus to reveal itself and face the immune system. This approach to an HIV cure is called 'kick and kill' – the kick is delivered from vorinostat, and the kill comes from the body's own immune system killer cells that have been trained by the vaccines.
Looking forward to possible next steps, Professor John Frater said: "We need to think about why we didn't see an effect. The important thing to realize is that despite these disappointing results, it does not mean that the basis of the approach is wrong. This is the very first randomized study of the 'kick and kill' concept in humans and the field now needs to work together to explore how better and more effective agents can have an impact on the HIV reservoir while remaining safe.
The vaccines used in RIVER, known as ChAdV63. HIVconsv and MVA. HIVconsv were highly effective at inducing HIV specific immune responses in the active group. Follow-up research may include giving further boosts of this vaccination together with a different kick drug or possibly using the 'next generation' of these vaccines that are now being trialed in other studies.
Professor Abdel Babiker of the MRC Clinical Trials Unit said: "Although the results are disappointing, they are unambiguous because of the randomization and completeness of follow up assessments. Because ART is so effective at reducing viral load, without the randomized 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."
Damian Kelly said: "The cost of HIV treatment globally and the new infection rates globally mean that we have to drive towards a cure for HIV or some in-between point such as remission. 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 randomized controlled HIV cure trial."