Dr. Alistair Paice: "I abide finding a cure"

— First of all we are about to ask you about the future trends. Now we have one pill or two pills instead of three, maybe injections – what will be next?

I think much of the work, scientific and clinical, of the last 10-15 years has been about getting the oral pills as good as possible.

And that’s not only making them as good as possible in the compounds that surround the chemicals but also making them as convenient as possible. You’re right about moving from lots of pills to smaller numbers of pills and then to once a day. And we are at this position now – this medication has a very good safety profile, good efficacy so orals can happen once a day. There is always room for improvement on that but still it is very good at the moment.

However, I think in the future clearly not everyone wants to take a tablet once a day. And one of the things that we have found is that there’re some people who are interested in other ways of taking the medication. So one of the things we’re really keen about is injections.

The idea is to give an injection for as long as possible. And we’re doing a lot of work to investigate that. At the moment we’re looking at the probability of giving an injection once a month or every two months.

A lot of the individuals living with HIV really want to find another way of taking medication, which they clearly have to take for the rest of their lives. And there is a variety of reasons for that: stigmas associated with having to take pills, carrying pills around and convenience as well. I’ll be honest – if I have to take a week’s course of antibiotics, I’ll probably forget, though I’m an adult. And I think it’s very challenging for people to remember to take a tablet once a day for the rest of their lives. And a lot of patients we speak to, a lot of patients I’ve spoken to in London said it would be great to do injections.

— Well, if we talk about injections – what kind of people would prefer them instead of tablets?

It is a very good question because in some ways our original belief was that people who had problems with adherence would actually want injections first of all. But that’s not necessarily the case.

You could be an airline pilot, a cabin crew or travelling all the time –why do you have to think about what time zone you’re at to take a tablet? Actually, the people who are really asking for it are the people who have been on antiretrovirals for five, ten, fifteen years, so they ask, ‘I’m taking my tablets all the time, I’m a good patient – is there another way of doing it?’

I think there are many types of patients who would benefit from that. Perhaps even those who we really didn’t think of it initially, perhaps even more so.

When we started to develop it we had a certain idea who we thought it would be for. Actually, maybe it is for a much broader group of people than we originally assumed. There are also areas in the world where it might be quite useful, so I cover the Middle East, Africa as well as Russia for my organization… And you know, in some parts of the world the stigma associated with HIV makes people unhappy and it is genuinely challenging for them to go forward and have a treatment.

Another group that is really difficult to treat are adolescents. If you’ve had HIV since childhood, you’ve gone through the difficulty of understanding your diagnosis as you were growing up, as a teenager… All of us as teenagers went through rebellious phases and I think of dealing with all of that as well. There are some clinics in London I deal with. They find there that for the adolescent transition patients injections will work really well.

— But won’t we have some problems with adherence? Because when it’s a daily thing like brushing your teeth or anything, you get history. But when it’s once a month, won’t we have problems?

We’ve already seen in clinical studies how happy people are about being on injections. And when we give them the option of going back to oral medication versus injections, the majority wants to stay on injections.

So let’s go back to the science. If you look at the length of time these injectable medications are staying within people’s bodies, actually that’s why they can be done for that length of time. But you’re right, the question is, what if you miss an amount of something? And I think that’s where we have to make sure that the clinics, the structures, the healthcare systems are orientated to help insure that this doesn’t happen.

I think you’re right, it’s something we have to be mindful of. Taking a tablet six-seven times a day and missing one every now and again is one thought but if you take an injection, you really can’t do this. So what we’re doing is trying to understand how it works.

— And I have one more question… an injectable PrEP… What do you do…

If we can’t get a vaccine, actually the closest way to a cure might be everyone having PrEP beforehand, so you can’t catch the disease.

If you have enough people protected with an injectable PrEP, although you have to keep on taking it – that is prevention. So that’s probably as close as we as a company are at the moment. Whilst it’s not an absolute cure, it’s a prevention to stop people getting the disease. We’re really excited about that.

— Well, two questions about PrEP. First of all in Russia and not only in Russia people say that when you don’t have money for HIV positive people or the pills for them, why do you spend money for HIV-negative people. How do you think this problem can be solved?

So again it’s both a clinical society and a scientific question. If you'll think about this logically, you're giving people with no illness a treatment, so they don’t get that illness. So we're doing a lot of investigations with cabotegravir at the moment to see for how long it stays in the body and to check the consequences for that long term as well. It is really important if we give healthy people a drug, we need to make sure that we're doing no harm to them. That is scientifically.

From the societal perspective this gets more philosophical. If we think, many individuals who suffer from HIV are some of the most productive individuals of society. And we still have an epidemic in some of the societies among the youngest individuals. Society has a duty to protect these individuals as much as possible for the future.

So that will be the discussion with Russian colleagues.

But certainly in places like Sub-Saharan Africa where the proportion of young males out of all the population is enormous. Society has to protect those. So if it involves taking something as PrEP to stop them getting an infection that is the right thing to do.  

— And the second problem of PrEP is that HIV-negative people have problems with adherence and a lot of them start PrEP without testing. So then we start having problems with the cure if they start PrEP being HIV-positive... And someday we can get the problem like ARV-resistant strains of HIV.

Again, I think it’s important for PrEP to be approached in an appropriate organized managed way. One of the issues with it is thatit is kind of not approved, people buy it on the Internet. Actually, I don’t know if you saw the Norwegian presentation just before lunch. They take it very seriously out of their healthcare system. They will fund it themselves. They provide support around it. And it’s about education. It’s about understanding what this is for and the risks associated with it as well.

Their presentation was excellent about the structure they have around PrEP, actually ensuring that individuals who are engaged even if they’re clean and they don’t have HIV, they engage with care. And let’s not forget that individuals who’re taking PrEP are still at risk of other sexually transmitted diseases, so there is an overall care package for this.

But I think it’s been structured and making sure that there isn’t just something that’s done without thoughtful process because as you say if it’s not done properly there could be consequences in the future which could impact in actual management of HIV.  

— While injections are still kind of the future, if we talk about one pill, we still have some problems...

To be honest it is probably more about the number of frequency during the day rather than the number of pills. We tend to find people are happy with one, two or sometimes even three pills once a day...

...Well, what is the point of reducing the number of pills if we already have one pill?

When we say ‘pills’ we actually mean ‘drugs’, so…

—  Yes.

So I think what we can’t forget is that people living with HIV will be taking medications for their entire lives. And it is our duty as doctors to try and ensure that for managing HIV appropriately, we reduce the amount of different molecules for people taking the drugs every day. That’s intellectual – every drug has benefits but has side effects as well. So the least number of drugs intellectually, the better it could be.

The standard management of three-drug regimens, which is clearly well established, is fine. But we actually believe if we associated it with dolutegravir, which is our molecule, it would be possible to do two-drug regimens. And that’s two different drugs. So we did it first looking at stable switch patients with dolutegravir and lamivudine and the studies demonstrated non-inferiority with that.  

So to your point what’s the benefit, well, at first we have to show that it does no harm – so it’s as good as three drugs. Then the fact that with less drugs taken at the same time, long term we should expect to show benefits. But clearly it takes time to get that kind of data.

So it is our belief that it’s better for individuals to have fewer drugs and now the modern drugs are available, we now start exploring these possibilities, we now start to get the data to back that up.

— One of the biggest problems is the price. A lot of people blame Big Pharma for high prices. What part of the price is the real science and development and what part is the profit? And is it possible to reduce prices using science? Do you have any perspectives there?

Yeah. I think it’s a fair question. I think, what needs to be remembered is that the science is going into these developments and there’re lots of molecules that fail. And it costs many billions of dollars to get a successful molecule to the drug stage. Now given that, we as a company have taken a position that we believe that, whilst we have made that investment and we’re developing it, we want to ensure that the drug is available as widely as possible. For example, one of my reaches is Africa, where things like the Medicines Patent Pool ensure that their Patent Pool is allowing generic versions of dolutegravir in South Africa. In Kenya, where I was recently, there are generic versions of that molecule available already.

So clearly we want as many people to be on it as possible. We are a company, we have to ensure that what we invest in generating it will get back. And we’ve made a commitment to ensure that the access is as wide as possible.

— Well if you talk about Russia – how much does Russia participate in some investigation in science? What are the perspectives of cooperation with Russia?

Excellent question. And actually fairly enough, we’ve been at the nearby Institute of Anti-Tuberculosis this morning talking to the director there. So I come to Russia a lot because Russia has contributed a lot to the science in my company. So we talked about our two GEMINI studies and two-drug regimens, and Russia’s contributed a lot of attempts and patience to each of those. So Russia is absolutely forward at the new technology for this.

We’re talking with investigators about how we’re very keen to continue because Russia does very well. They’ve contributed so much to the science and we expect that to continue.

The other thing that we’ve been talking with investigators about is their own studies, both real world data – data of implementing new molecules – and also general investigation studies of things that are of interest to local investigators to see whether we could support those as well.

If I reflect on real world data one of those components: one of the publications that was in Amsterdam was really impactful. It was the Brazilian Ministry of Health publication – they’ve had a wide scale implementation of dolutegravir as a program implementation working with the IV, so they switched the whole program from efavirenz to dolutegravir.

And they showed as a mark of efficacy getting their viral load below fifty c/mL, they showed twenty one percent improvement in a total program switch so this is real world data. Well the clinical data is fantastic, the clinical child data is fantastic but is also really important for us to see what that actually means in practice. We would be very keen to do similar studies, if it’s possible, in Russia as well. Ought to say that.

So science is fantastic but seeing implementation and what it means in practice is also of great importance to us.

— Well then I have the last question probably about far or maybe not far future. How soon do you think we can cure HIV?

I’ll be honest. But I would love to meet people to do this, honestly, I would. I abide finding a cure. I worked in previous companies where we had a vaccine, and it seemed like a good idea but unfortunately it didn’t work. There is a whole stream of work within our organization with big US cure canters looking for a cure. I think I’m honest. There are many fossickers finding a cure.

And in some ways there are two types of cure. There is absolute cure like a vaccine or there is a functional cure. And we saw on some of the presentations today we’ve seen recently that you know if your viral load is down below fifty copies per ml, the virus is non-transmissible. So if we get everyone below fifty, clearly people with the virus will keep the virus but actually no one else in theory would acquire it. So that is one approach and perhaps the injectables we talked about are an approach for that.

Absolute cure like a vaccine… There are great advances happening in the science but I think that is near to medium future.