#05: Hope for a cure

Femi Oke:

Welcome to HIV unmuted, the IAS International AIDS Society’s podcast. I’m your host, Femi Oke. Forty years since AIDS was first reported, it’s time to reflect on where we are, consider how far we’ve come as we move towards an HIV cure and the hope that would provide.

In 1981, AIDS was first recognized by doctors in Los Angeles. Just two years later, scientists discovered HIV, the virus that causes AIDS. But the rest of the ’80s was marred by rising deaths worldwide and no cure in sight.

The discovery of effective HIV treatment in the mid-1990s ushered in a new era of hope, but only if you could access and afford the expensive medications. However, an HIV cure, like the vaccine, proved elusive and still evades scientists today.

I asked leading HIV scientist and IAS President-Elect, Sharon Lewin, why HIV is so hard to cure.

Sharon Lewin:

HIV is a tough virus to deal with. It’s got some important tricks up its sleeve. Its most powerful trick is that it becomes part of our own DNA. It gets inside certain cells and then it gets inside the DNA. Therefore, the virus stays with you for the lifespan of that cell. That is very different to almost every other virus.

Either you’ve got to chop it out somehow or get rid of the cell that it’s infecting. And that’s the big challenge.

Femi Oke:

HIV treatment continues to improve. Today, it enables people to live long, full lives. Plus, thanks to the science of U=U, people living with HIV on treatment cannot pass it on sexually. Yet the discovery of an HIV cure remains as important as ever.

Sharon Lewin:

It’s very easy to think that HIV has gone away, that it’s no longer a big problem. It is still a major pandemic. People still die. There are millions of new infections every year and it just changes the course of people’s lives. And so, a cure would be just transformative.

Femi Oke:

For decades, there was no hope for a cure. But that’s starting to change. Thanks to a small handful of people who have been cured of HIV, we now know a cure is scientifically possible.

Sharon Lewin:

You’re right. There are people that have been cured. And it’s a small number. We divide cure into people that are truly cured, meaning we can’t find any intact virus in them, and people that can keep their virus under control at very low levels and therefore don’t need treatment. We distinguish between these two types of cure.

Sharon Lewin:

People with the true cures, or absolutely no intact virus, are very rare. There’s maybe five in the world. Three of those cures have happened after receiving a bone marrow transplant.

Femi Oke:

So, there are two types of cure, and they’re rare. We’ll hear stories of both later.

But first, let’s dig deeper into why a cure is so important. For that, we travel to Uganda and go back to the 1990s.

Moses Supercharger:

I’m called Moses Supercharger, living in Kampala, Uganda.

Femi Oke:

In the 1990s, Moses was a well-known musician and radio DJ, with many admirers. He had heard some of the myths surrounding HIV.

Moses Supercharger:

My girlfriend warned me about sleeping with people’s wives, that man can send you witchcraft that can make you sick every day, make you thin, lose weight, and so forth. I could not listen. I continued misbehaving until 1994, when I began falling very sick. I was advised to go and take an HIV test, which came out positive. And it really shook me so much.

Femi Oke:

In 1994, drugs that were reaching the US and Europe were difficult to come by across the continent of Africa.

Moses Supercharger:

At that time, HIV was considered a death sentence. I thought I was going to live for one, two to three years. I was alone and frightened.

Femi Oke:

For four years, Moses put off starting medical treatment.

Moses Supercharger:

I did not start treatment until 1998. I resorted to witchcraft because we all have this problem of myth and misconceptions around HIV.

Femi Oke:

But in 1998, he realized witchcraft was not the solution. He began drug therapy despite the extraordinary expense.

Moses Supercharger:

When I started the real treatment in 1998, it worked very well. But remember, at that time, we had to buy the medications ourselves. And I couldn’t afford them. So I resorted to taking tablets on and off.

Femi Oke:

Skipping his tablets resulted in Moses developing HIV drug resistance, meaning his medication no longer worked.

Moses Supercharger:

Around 2000, I developed what they call HIV drug resistance simply because I was not taking my medications correctly. And I didn’t know.

Femi Oke:

Moses was on death’s door, so near to the end that his family began preparing for his funeral.

Moses Supercharger:

Their major concern was that, when I died, it would be very expensive for them to take my dead body to our ancestral home, which is around 150 miles away from Kampala, where we were living. They decided that I should be taken by bus the following day, which was cheaper.

Femi Oke:

Passengers on the bus soon complained about Moses vomiting. As a result, he and his family were kicked off and left on the side of the road. A kind stranger took pity and drove Moses home in the back of a pickup truck, next to his coffin.

Moses Supercharger:

I made the rest of the journey home in the back of the pickup, next to my coffin and the items for my burial. It was terrible.

Femi Oke:

As his family gathered, Moses clung to life for three days, long enough for his sister to arrive home from abroad.

Moses Supercharger:

My lovely sister, Sarah, was abroad at that time. But when she returned to the village, she was like, “No, it can’t be. You can’t give up on somebody.” So, she organized transport to take me to a specialist, called Joint Clinical Research Centre. My sister is the one that saved my life. And I love her so much.

Femi Oke:

Moses was put on a new drug regimen, saving his life. Today, he continues to take his medication religiously and on time. He honoured his sister, Sarah, by giving his own daughter the same name.

The story of Moses illustrates why a cure is so important. Taking HIV drugs daily, as prescribed, is not easy or possible for many. This can be because the drugs are too expensive, because of stigma, because of a lack of education about the risk of skipping medication, because of the side-effects, or because a crisis like COVID-19 disrupts the supply chain. There is a multitude of reasons.

Femi Oke:

A cure would end the need for ongoing treatment and change the lives of people living with HIV.

Moses Supercharger:

The cure of HIV is so important to people living with HIV because we are denied love and marrying the people we want. Because of our status, we are denied opportunities, we are denied jobs. We think when the cure comes, all that will change.

Femi Oke:

While we don’t have a cure that is accessible to all yet, at least two people have been cured with medical intervention. One is known to the world as the “London patient”.

Adam, the London Patient:

I am Adam, the “London patient”, the second man cured of HIV. And I want to give a message of hope, as an ambassador of hope. Adam is a regular guy who wants to be successful in life and, like anybody else, wants to work and have a family and have a good life.

Femi Oke:

But Adam wasn’t always so positive about his future.

Adam, the London Patient:

When I was diagnosed with HIV in 2003, as I’ve said many times before, it was like a death sentence to me. Because when you got HIV, you’ve been told you have 10 years maximum; you’re lucky if you get 20.

Things have changed, obviously. But that’s what I had: I had a death sentence at that time.

Femi Oke:

Less than a decade later, Adam would be rocked by another diagnosis.

Adam, the London Patient:

By 2011, 2012, when I was diagnosed with cancer, I had to re-live emotions about having a death sentence again and feel overpowered with anxiety, fear and stress. That was a very painful part, to re-live all of the emotions. And that was very challenging for me.

Femi Oke:

Adam’s last hope of cancer survival was a bone marrow transplant. But he never could have foreseen what would come next.

Adam, the London Patient:

I was on a double-decker bus, an iconic British institution. I was going to see one of my doctors on that day. And I received a call from the transplant team, the haematology teams, who said to me, “I got great news for you: we found a match.”

And I was just thinking, “What else are you going to give me?” And they said, “Well, we think we can cure your HIV.” And I was like, boom.

Femi Oke:

Boom, indeed. Imagine staring down death’s door, only to be told that there was a chance not only to cure your cancer, but to be cured of HIV, as well.

Adam, the London Patient:

I was on the bus and I started just laughing to myself. And, wow. I said, “I won the lottery.” Because, for me, my health … it wasn’t about money. For that moment, the “London patient” story began.

Femi Oke:

One doctor has been a key part of Adam’s story. Ravi Gupta led the research team responsible for Adam’s transplant.

Ravi Gupta:

I first met Adam back in 2015 during the summer. And the reason I’d met him is because I was working on cellular biology. As well, I was working on HIV reservoirs and how HIV was able to infect cells and the molecular mechanisms of some of that. And people in the hospital knew that I was working on these reservoirs.

Ravi Gupta:

Adam, essentially, had tried many different treatments to cure his lymphoma. And it had all failed. And the doctors at Imperial College had arranged a transplant for him.

Femi Oke:

The bone marrow transplant created an opportunity to cure Adam of HIV. To understand how, first let’s take a look at a major discovery made in the 1990s.

Ravi Gupta:

Remarkably, research in the ’90s showed that there was a certain group of people who were completely immune to HIV. In other words, they couldn’t be infected despite exposures. And these individuals were found to have a defect in the CCR5 protein. In other words, it was a genetic defect affecting both inherited copies of that gene. And this was called delta32 in the CCR5 gene.

Femi Oke:

The hope was that if Adam could get a transplant from someone with this genetic mutation, then he would be cured of both cancer and HIV.

This had been done only once before, to Timothy Ray Brown, globally known as the “Berlin patient”.

Timothy Ray Brown (sound clip):

I got the transplant. And by the third month after that, I didn’t have any detectable HIV in my blood.

Ravi Gupta:

With Adam, we tried to do the same thing. We identified a donor who had this genetic defect.

Femi Oke:

After medical and ethical clearances, Adam underwent the procedure despite the dangers.

Ravi Gupta:

In the procedure that the “Berlin patient” undertook, the transplant would’ve had a 30% mortality or something like that – in other words, a three in 10 chance that you die as a result of it. In the case of Adam’s treatment, it was probably more like 10%. But a one in 10 chance of dying is still pretty high stakes.

Femi Oke:

Adam survived the transplants, but the recovery was a long, arduous process.

Adam, the London Patient:

Through my transplant and over my recovery, it was very painful. [inaudible 00:12:42] regained how to talk, how to walk. I just started from zero. It was very challenging, as I said before, highly risky because you can die at any time. You have to hang on there every day and think, “It’s one more day.”

Femi Oke:

Adam fought every day to regain his strength. Today, years after the transplant, he is cured. But the effects of the transplant linger.

Adam, the London Patient:

I still struggle with some of the side-effects of the transplant – fatigue. And you get complications from time to time. You can get secondary cancers. It is not an easy road. People just think it just happened. It’s a journey and I’m still on it.

Femi Oke:

Adam’s incredible journey has led him to speak around the world and let people know that even though his path to a cure can’t be replicated for most, it opens up a door to finding a cure for all.

Adam, the London Patient:

I want people to hear my story, to give hope. It’s important to give hope. I know a lot of people have said, “Well, it’s not very feasible. It’s not workable for many people.” But I want to say to people, “This is the door for a cure. This is the beginning.”

Femi Oke:

There are also others who are thought to be cured of HIV without risky medical procedures. They have naturally eliminated the virus from their bodies.

Femi Oke:

Sharon Lewin recently co-authored a paper about this phenomenon.

Sharon Lewin:

This woman had a period of being on antiviral therapy during her pregnancy. But when she was off treatment, the researchers tried to find virus in billions of cells from her blood – and they also actually looked inside the placenta because when she had her baby, they managed to also store and analyse the placenta.

And despite looking at billions and billions and billions of cells, they could not find an intact virus, which means a virus that had all the right components to it. They could find fragments of the virus, but no intact virus. And she’s not on treatment. And she’s had no detectable virus in her blood using standard assays for many years.

Femi Oke:

This woman is known as the “Esperanza patient”.

Sharon Lewin:

She comes from a town called Esperanza, which means hope. … I’m sure her story has given many people hope. But she’s decided not to reveal her name at this point in time.

Femi Oke:

These stories of a cure provide hope to people living with HIV and a path for scientists to follow.

Sharon Lewin:

We divide our thinking around cure strategies in three areas. There’s what we call combination immunotherapy, which means a combination of interventions that get the virus as low as possible and also boosts the immune system. And they’re the approaches that have worked well in animal models. And there are many clinical trials now, looking at combinations of either crushing down the virus to small levels or really enhancing the immune system with vaccines or antibodies or other drugs that modulate your immune system.

The other two sit under the umbrella of gene therapy, which means using gene scissors or ways to edit or remove, say, the virus itself, or the receptor the virus uses. And there are two ways you can do that. You can do the outside the body. You take cells, you modify those cells, and you put them back in: what we call ex vivo (outside the body) gene therapy. Or you can do it directly in the body, in vivo gene therapy, where you can inject the gene scissors or inject the gene that you want the person to express. And that’s another way that you can also enhance the immune system.

Femi Oke:

The science is promising. But now that there is effective treatment available for people living with HIV to lead long healthy lives, Sharon is often asked why an HIV cure still matters.

Sharon Lewin:

I’d love to see HIV eliminated, non-stigmatized, and to give people a range of options once they get diagnosed – rather than saying, “Here, there’s some fantastic drugs. But you’re on them for life.” The drugs are great. And people living with HIV should not fear being on those drugs. They’re life-saving. They stop transmission. They’re very easy to take. But you’re on those for life.

Probably the biggest driver for why we need a cure is that to keep 37 million people on treatment, which is currently the number of people living with HIV, it is estimated to cost about $30 billion a year. That’s a big cost to the system.

Femi Oke:

Forty years ago, when AIDS was first discovered, there was hope for a cure. But as time went on, hope faded away. Yet, scientific advances over the last decade have shown that a cure is possible.

Femi Oke:

Adam, the “London patient”, looks forward to seeing the number of people cured of HIV continue to grow.

Adam, the London Patient:

I hope my family grows and grows over the years and we don’t talk about HIV as an incurable disease. I want a lot of people in my family. I open and close my eyes, and I see hundreds of people around me.

Femi Oke:

Adam’s cure was incredible, but it’s not a cure for everyone. We still need a cure that is safe and can be accessed around the world. So, when will that happen?

Sharon Lewin:

It’s really hard to predict that, when we’re likely to have a cure. I think we’re still decades away.

Ravi Gupta:

I don’t think we have a cure in the sense that people would like or that the average person on the street would define as a cure. We have been able to achieve proof of principle, so that’s one step in the right direction. I think that we’re making small steps, but it’s still a little way off.

Femi Oke:

In Uganda, Moses Supercharger is now an advocate for an HIV cure.

Moses Supercharger:

To the researchers all over the world, nobody believed that there would ever be a person cured of HIV. But when Timothy Ray Brown was cured, everyone was shocked. We now have a proof of concept that a cure is possible.

To all the researchers who are searching for the HIV cure, we are proud of you. Don’t give up. Keep trying, keep trying. I know the cure will come one day.

Femi Oke:

Here’s a final thought. There are 37.7 million people living with HIV around the world, but stigma and lack of access to services keep many from even being tested. And of those who know their status, many simply don’t get the medical care they need. For those who can access treatment, drug therapy can be costly and too often stigmatizing.

A cure for HIV would change the lives of people living with HIV forever. That’s why it is so important to keep following the science. Stories like the Berlin, London and Esperanza patients show that there is hope; it is scientifically possible to cure HIV. But to achieve a scalable cure in our lifetime requires more than just hope; it requires political commitment, funding, community involvement and us all to re-engage in the HIV response.

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In a time of dual pandemics, we cannot allow scientific progress in the HIV response to falter. The discovery of a safe and effective HIV cure would move us closer to a world in which HIV no longer presents a threat to public health and individual well-being. 

Read our World AIDS Day message: iasociety.org/WAD2021

The IAS Towards an HIV Cure programme drives concerted efforts to accelerate global scientific research and engagement towards a cure for HIV.

Find out more at iasociety.org/ias-programme/towards-hiv-cure

When can we hope to realize a safe and effective cure for all? Enjoy this seven minute musical production by Moses Supercharger and the Stigmaless band.

Watch now: www.youtube.com/watch?v=VQmWVxwHiFo