Professor John Frater is Principal Investigator and Scientific Lead of the University of Oxford’s role in the CHERUB project (Collaborative HIV Eradication of Reservoirs: UK BRC) – a platform that explores strategies for HIV eradication in the UK. This project aims to push forward the boundaries in this new field.
It is increasingly apparent that highly active antiretroviral therapy (HAART) may not be the long-term solution to the management of HIV infection, and that other avenues need to be explored. As a result of various recent cases, the idea of eradicating HIV altogether is becoming less unimaginable to some scientists.
Ultimately, medical research must translate into improved treatments for patients. At the Nuffield Department of Medicine, our researchers collaborate to develop better health care, improved quality of life, and enhanced preventative measures for all patients. Our findings in the laboratory are translated into changes in clinical practice, from bench to bedside.
Q: Why is antiretroviral therapy not the long term solution to HIV?
JF: Antiretroviral therapy is fantastic. Over the last 20 years or so, there has been a revolution in how we understand how one might treat an infection like HIV which, initially, 25 years ago we thought we may not be able to treat. Therapy has changed lives. Life expectancy now if you were to become HIV positive tomorrow is probably the same, or very close on being the same, as if you were HIV negative, so therapy has done incredible things. There are issues though in terms of the provision of therapy. Can we get therapy to everyone who needs it? And at the moment it doesn’t look like we can. There are cost implications with therapy. It is incredibly expensive. Prices are coming down but the management of HIV in this country alone is around £1 billion per year, so it is expensive, including everything that goes with it. But I think more importantly than that, despite being on therapy there are risks of toxicities, there is the risk of drug resistance, and people are still getting illnesses despite being on therapy with the impression that therapy is working. So it is not the complete answer and therefore we are starting to consider whether we need to look for other potential options and ways of treating HIV.
Q: What is the alternative?
JF: There are a number of different alternatives. One alternative would be to prevent getting it in the first place. There are a number of ways of trying to change human behaviour: condom use, changing sexual practices, things like that. But human behaviour is notoriously difficult to change and there have been a number of attempts. Some countries have done very well, such as Uganda, in terms of trying to change things like condom usage. But globally it hasn’t made much impact. Certainly in the UK people are still turning up with new HIV infections even though they know the risks. So this is something that is on-going, there is an on-going number of people catching HIV. The other option would be to develop a vaccine. We have spent millions of pounds and dollars trying to develop a vaccine and yet we have nothing at the moment, and some people feel that there may never be an HIV vaccine and that is obviously of a concern, although there’s still on-going research. Then the third line would be to think about eradicating HIV. If you’d have asked someone 5 or 10 years ago they would have said that is a completely crazy, ridiculous idea. But more recently, with certain scientific breakthroughs and a greater understanding about how HIV works there is just a feeling that this might be possible or it might be worth exploring just in case it is possible. So there’s now been a sort of global interest in seeing if actually curing HIV or even eradicating it is a possibility.
Q: Is it possible to consider a timescale to eradicate HIV?
JF: You can consider a timescale but whether I can actually give you one I think a different ballgame. This is an extremely long-term project. There are still some people who would still say that it is completely impossible. Saying that one person has been cured of HIV. There’s a famous case of a patient who became known as the Berlin patient who developed leukaemia at the same time as HIV. The chemotherapy and the stem-cell transplants that he had in order to cure his leukaemia also cured his HIV infection. Now this is incredibly toxic, you wouldn’t want to give this to everybody. It is not a global answer, but it shows that it can be done. More recently there have been two other cases now that look like they may also have been cured of their HIV infection, again through bone-marrow stem-cell transplantation. So there’s a gradual feeling that it may be more possible than it was before. In terms of timescale, certainly not in the next 10 years – when we have worked out how it works, how it behaves, where it’s hiding, then we need to try and get it out and tackle it that way.
Q: What are the most important lines of research that have developed over the past 5 or 10 years?
JF: The key thing in order to cure HIV and in order to take research for HIV forward has been the basic laboratory work to try and understand where the virus is hiding in the body – is it hiding in the blood? In the lymph nodes? In other tissues? And try and actually discover where these ‘reservoirs’ (which is what we call them) where the virus is hiding and where it’s hiding from therapy. Once the virus is in the reservoir the therapy won’t work. The work that’s been done to figure out where in the body it is hiding is absolutely critical and that’s still on-going. The other completely critical piece of work is therapeutic interventions and new technologies to try and get this virus to come out of hiding so therapy can be used to kill it. There is a new class of drugs that has been around and used by the oncologists for cancer for some time, and it would appear that those drugs also work on people with HIV infection. A recent paper published by an American group suggests that if you give these oncology agents to people with HIV it causes the virus to wake up. So I think this now allows us to take that research forward and take on new trials and explore these agents to see if we can use them.
Q: So why does your line of research matter? Why should we put money into it?
JF: I think you could ask the patients that question. People are fed up of taking tablets. You have to take pills every day for the rest of your life. Just impacting your normal life – the stigma associated with it, there’s toxicity, there is having to remember because if you forgot a few tablets there’s a risk of resistance so it makes an enormous impact. Yes the patients stay well if they take their tablets, but the burden of having to do that every day, sometimes secretly if they don’t want other people to know, is really significant. And that’s on top of the fact that not everybody who needs therapy is getting therapy. So I think looking for different approaches is critical.
Q: How does your research fit into translational medicine within the department?
JF: I think this is about as translational as it gets. This is taking research from the laboratory straight into clinical trials to be used with patients. The work that we do involves having researchers in the labs pipetting blood samples and looking at cells, and at the same time we have clinical trials where the information we learn is applied to patients taking these new therapies to see how they do. So that’s about as translational as you can get!