EATG » What’s the fuss about a functional cure?

What’s the fuss about a functional cure?

A cautious overview of the Hong Kong study by Miranda Smith

A recent study from researchers in Hong Kong has got the world’s media talking about a functional cure for HIV. A quick search for the terms ‘HIV, functional cure, Hong Kong’ yields a long list of articles and videos from around the world. Twitter has also been going crazy. Read on to find out what the researchers did, what they found, and more importantly, what this means for people living with HIV.

What did the researchers do?

The University of Hong Kong team was led by the internationally respected researcher Zhiwei Chen. The team made a new type of antibody and showed in proof-of-concept experiments that could be used to prevent HIV infection, or to treat existing HIV infections. It is important to note that these experiments were done in mice, not in humans.

The new antibody is an engineered molecule that contains binding sites for both the HIV envelope and the human CD4 molecule. The researchers tested different molecules based on known broadly neutralising antibodies (read here for more info). They tested different molecules for their ability to block HIV, either alone or in pairs. The most potent combination were then selected and combined into a single molecule. Two important features of this molecule are that it is made from a single gene that includes both binding sites and that each binding site is present twice.

The researchers tested this molecule (called BiIA-SG) against a wide range of HIV strains in cell culture experiments, and found that it was able to neutralise (block) 100% of the 124 strains tested.

Cell culture is one thing, but what about in an animal model? The researchers also did two important experiments in humanised mice. Humanised mice are common in HIV research as regular mice cannot be infected with HIV. Humanised mice are immunodeficient mice that are given human immune cells (including CD4 T cells) that can then both be infected with HIV and mount immune responses to infection.

What did the researchers find?

The first mouse experiment looked at BiIA-SG as a preventative measure. Groups of mice were given either a single dose of BiIA-SG or a placebo, and then infected with HIV. None of the mice given BiIA-SG showed any sign of infection, while all of the placebo-treated mice became infected with HIV and showed high levels of virus and CD4 T cell loss over time.

The second mouse experiment looked at BiIA-SG as a therapeutic measure. Here, the BiIA-SG was given as a genetic construct instead of a protein which the researchers showed results in a longer half-life of BiIA-SG in the body. Groups of HIV-infected mice were given either a control construct, or low, medium or high dose of the BiIA-SG construct. Most animals given the medium or high dose BiIA-SG construct showed eventual control of virus which corresponded with the accumulation of BiIA-SG in their plasma. The animals which controlled their virus also showed a reduction in HIV-infected cells in the blood and spleen.

What does this mean for people living with HIV?

This work is an important proof-of-concept for the development of potent, broadly active molecules that could be used either to prevent or treat HIV.

While the results are quite exciting, there are still a huge number of unanswered questions. How stable is the molecule in humans? What are its pharmacokinetics and pharmacodynamics? Would the molecule reach the tissues necessary to prevent reservoir formation? Is it effective on the existing reservoir? Does the molecule generate anti-drug antibodies? What about viral escape?

This molecule is still a long way from being a functional cure. The next step will be either testing in non-human primates or small scale proof-of-concept studies in humans. Even if this next stage is straightforward, BiIA-SG would be a treatment that would most likely need to be given every few months. With long-acting antiretrovirals on the horizon, a treatment like BiIA-SG will not be dramatically different unless it is able to clear the HIV reservoir. It is a step in the right direction, but there’s still a long way to go.

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News categories: Cure, Scientific research