Broadly Neutralising Antibodies: The future of HIV care?

On Wednesday 6th November 2019 the community groups came together at the European AIDS Clinical Society (EACS) conference in Basel to discuss the pathway to achieving long-term remission of HIV. 

It's important to point out that we're using the term 'long-term remission' rather than 'cure' because cure is a word that has many meanings and interpretations - where as remission is more specific. 

Annemarie Wensing from University Medical Centre Utrecht talked the group through the potential of Broadly Neutralising Antibodies (bNAbs) to achieve long-term remission.

bNAbs are human antibodies which stimulate and improve the body's immune response to a virus - in this case HIV. Your body's the natural development of antibodies can take a long time during which the virus can mutate so those antibodies are no longer effective. So to circumnavigate this problem it is possible to clone monoclonal antibodies in the laboratory, these can then be engineered to improve their flexibility and half life - these can then be delivered to the patient. 

Trials in rhesus monkeys with a single bNAb were initially successful but eventually failed with viral rebound, a trial with two concurrent bNAbs showed promise but half the monkeys had a natural resistance which led to a lack of effective immune response. A third trial where bNAbs were combined with a traditional ART regimen gave much higher levels of success without viral rebound.

Approaching from another angle bNAbs have been trialled on rhesus monkeys as pre-exposure prophylalxis. The monkeys were given a single injection of bNAbs and this provided effective protection for a median of 20 weeks. Whilst this approach is a long way off in humans is shows there is a possible new approach to PrEP.

Another approach, ICISTEM, in which HIV positive individuals who require a stem cell transplant are given a transplant from a donor who has some natural HIV immunity have produced two patients in long-term remission - although this remains an incredible dangerous procedure.

Simon Collins of HIV i-Base in the United Kingdom presented information from the RIO study which is investigating dual long-acting bNAb therapy.

One of the benefits of using bNAbs over traditional HIV therapy is that because they all attach to the virus in different sites if you develop resistance to one bNAb you that resistance won't apply to other bNAbs.

The study which is currently going through ethics approval will see the patients randomised into two arms with patients in the bNAb arm receiving two bNAbs from the Rockefeller Institute.

The two stages are:

• Stage 1: placebo controlled double-blinded two arm prospective phase II controlled trial.
• Stage 2: patients in the placebo arm in stage 1 will be offered to receive dual bNAb at ART restart once viral rebound criteria has been achieved. 

It's clear that there is much ongoing research into using bNAbs and stem-cell transplants and there appears to be promise in both avenues, however these are still a long way off being viable treatment options. People living with HIV should continue to take their prescribed anti-retroviral treatments.