Man

It multiplies incredibly fast...

NARRATION
Looking back at 30 years of HIV research, it's clear we've come a long way. The advent of new medications means those with HIV are living longer, healthier lives.

Nicholas Parkhill
In effect, what treatments mean is diagnosis does not equal death.

NARRATION
Nowadays, many people think of AIDS as a Third World disease. But in reality, it's right amongst us.

Nicholas Parkhill
We ARE seeing a resurgence in HIV. I think younger people perhaps have a different relationship to HIV.

Professor Stephen O'Brien
They're growing up, and some of them are careless, like young people are. You can't scare them because they think that the drugs will save them.

NARRATION
HIV/AIDS is still one of mankind's greatest scourges.

Professor Stephen O'Brien
It's still a terrifying diagnosis to get as a young man or woman that you're HIV-infected.

NARRATION
The Holy Grail of HIV research is to find a cure. With the imminent threat of drug resistance, doctors have a new weapon in their arsenal.

Associate Professor Paula Cannon
These new types of medicine based on genetic manipulation of our cells, I think this is an exciting way to think about fighting HIV.

NARRATION
I travel abroad and talk to scientists who are making medical history. And I meet the man who is living proof that a cure is possible.

NARRATION
A deadly virus jumps from primates to humans.

Reporter
Meanwhile, the silent killer continues...

NARRATION
It spreads around the world before we're even aware it exists.

Presenter
Acquired Immune Deficiency Syndrome looms as the greatest health crisis to face this country in a generation.

NARRATION
HIV/AIDS would go on to become the worst pandemic of our time, infecting 70 million people and killing 35 million.

Associate Professor Paula Cannon
You know, the big problem with HIV is it's not just your average virus that infects any cell in the body. It's a virus that specifically goes into your immune system and kills the very cells that are trying to attack it. That's why it's so insidious.

NARRATION
HIV homes in on T lymphocytes, or 'T cells', our vital immune cells that help fight infections. It penetrates the T cells' defences and begins to replicate up to ten billion copies a day. Eventually, the cell dies, releasing new clones of the virus, slowly killing off a person's immune system. Medications can stop the virus from replicating. But HIV is cunning.

Associate Professor Paula Cannon
Oh, my gosh, it's like the poster child for natural selection. It's always changing. If you treat patients with just one drug for example, the virus just laughs at you and very rapidly evolves resistance to that one drug. This is why we have to treat patients with multiple drugs, typically a combination of three, to make it just statistically improbable for the virus to be able to simultaneously evolve resistance to all three drugs.

NARRATION
HIV is able to lie dormant within cells for months or years.

Associate Professor Paula Cannon
So that cell looks like a normal cell. The body's immune system can't tell that it's got any virus in it. But then, down the line, something happens to that cell to kind of wake it up, and wake up the HIV virus inside it. So that's why no matter how long a patient takes these drugs, we can never get rid of these very rare, latently infected cells that are just prime to restart the infection.

NARRATION
But new research holds promise of ending a patient's lifelong dependence on drugs. It was in Washington DC that I met Timothy Ray Brown - the only man in the world to be cured of HIV.

Timothy Ray Brown
It's amazing to be cured of HIV, and I'm very happy about it.

Dr Maryanne Demasi
Did you believe it at first?

Timothy Ray Brown
No, I didn't believe it at first.

Dr Maryanne Demasi
What finally convinced you?

Timothy Ray Brown
A medical journal was published, and I realised that a lot of other medical scientists believed it, and so then I started to believe it. But it took awhile.

NARRATION
Tim reflects back on how his cure came about. Living in Berlin at the time, his HIV was under control - until one day he began to feel unwell. After a battery of tests, his doctors said those dreaded words.

Timothy Ray Brown
He said, 'I have bad news for you. You have acute myeloid leukaemia.' And I'm like, 'Oh, crap.' And I was in shock.

NARRATION
This type of leukaemia is most likely to be a death sentence for HIV patients.

Timothy Ray Brown
He explained to me that there was a chance that they'd have to do a stem cell transplant. And at that point, I'm like, 'OK, I guess I'll have to go through this in order to live.' Because the leukaemia would have killed me like within a couple of months.

NARRATION
Tim wasn't to know that the bone marrow transplant he was about to receive would make him one of the most famous medical patients in history. It began with a discovery made by Professor Stephen O'Brien. He noticed that some people were more vulnerable to HIV infection than others.

Professor Stephen O'Brien
We knew that some people became infected easily while other people were exposed many times and avoided it.

NARRATION
Professor O'Brien searched for a genetic explanation for why some people were less likely to be infected with HIV.

Professor Stephen O'Brien
At that time, the human genetics industry was in its infancy. A decade after HIV, we were talking about sequencing the human genome, and AIDS had started to take tens of millions of people. The tools for studying these things were getting us to the stage that we were able to design strategies to see if we could discover a natural genetic resistance.

NARRATION
A breakthrough came with the discovery of a receptor on the surface of T cells called 'CCR5'. HIV initially docks with the CD4 receptor, but then needs to bind to the CCR5 receptor to invade the cell. Remarkably, Professor O'Brien's lab discovered some people were born with a genetic defect resulting in a faulty CCR5 receptor. When the receptor is defective, the virus can't enter the cell.

Professor Stephen O'Brien
It was as if, if you had two copies of this mutation, the deletion that ruined CCR5, you never got infected with HIV. So this convinced us that CCR5 was necessary for infection.

NARRATION
Professor O'Brien published these findings in 1996. Today, it's estimated about 1% of the Caucasian population has inherited this genetic defect and are naturally resistant to becoming infected with HIV.

Associate Professor Paula Cannon
You, I, any people, you know, watching the program can be CCR5 negative. You can get HIV in your body and it can't get into these cells. It puts one foot on CD4 and the other foot kind of has nowhere to go. So people who are CCR5 negative are resistant to HIV.

NARRATION
It was a fortunate coincidence that Timothy's doctor came across Professor O'Brien's paper while studying as a med student. He was fascinated by the idea of HIV resistance.

Dr Gero Hutter
I was so impressed from this research that I kept this information in my mind, and, ten years later, when I saw the Timothy Brown patient, I put one and one together and decided to make this approach.

NARRATION
Doctor Hutter hypothesised that if he could find a bone marrow donor that was not only a tissue match but also had the mutation of the CCR5 gene, Timothy would have a shot at being cured of cancer as well as HIV. This procedure had never been done before. And the odds of finding the perfect donor were slim. But they had success. Timothy was infused with the donor cells, and Dr Hutter waited anxiously for the results.

Dr Gero Hutter
After 60 days, the testings for virus material were all negative, and stayed negative. So this was the time frame probably where the eradication happened. It was a very good moment.

Timothy Ray Brown
I'm sure I'll go down in history as being the first patient that has been cured of HIV.

NARRATION
Tim is now famously known as the 'Berlin patient'.

Timothy Ray Brown
There are 34 million people in the world with HIV. And it's hard to believe that I am the first person to be cured of HIV, it's hard to believe.

Professor Stephen O'Brien
It's not a general procedure that we can turn around and say, 'OK, all you HIV-infected people, we can do these bone marrow transplants.' They require lifelong immunosuppressive drugs, they have the risk of graft-versus-host reaction, which kills something between 25% and 30% of the people who receive these bone marrow transplants. And because it doesn't always work. So it's only a treatment of last resort.

Dr Maryanne Demasi
It's been several years since Tim had his treatment, and, despite hundreds of blood tests and tissue biopsies, including in his brain, doctors have never been able to find a shred of HIV in his system. Now, researchers around the world are scrambling to develop a streamlined version of this therapy that's safe and accessible to everyone.

NARRATION
Here in Los Angeles, researchers may have the answer in using one of the most sophisticated tools in genetic engineering.

Associate Professor Paula Cannon
So the question is - can we take somebody who has CCR5 and genetically alter their cells so that they no longer have CCR5? And by doing that, can we make somebody's immune system now resistant to HIV so that they can fight back and start to stop this virus spreading in their body?

NARRATION
To do this, her team used what they describe as molecular scissors, which cruise along the DNA until it finds the CCR5 gene.

Associate Professor Paula Cannon
I want to go into the DNA and basically make a cut in the middle of that CCR5 gene and just kind of mess it up so that it can no longer make the CCR5 protein. And if we introduce them into a patient's cells, they'll basically go in, they'll hunt around in the DNA, they'll find the CCR5 gene and they cut it, and in that way they destroy it.

NARRATION
Matt Sharp was prepared to put his body on the line to trial this technology.

Matt Sharp
As somebody who's been living with HIV and taking these medications for years, my concern was really to improve the state of the art. How can we get beyond having to take medication for the rest of our lives?

NARRATION
Matt is on medications, but for some reason the virus always had the upper hand on his immune system. And his T cell count remained low.

Matt Sharp
Most people that go on antiretroviral therapy, their T cells will start to climb and almost get to a normal level. Mine never have over the years.

NARRATION
At the clinic, a nurse takes his blood to siphon off his T cells.

Grace Gonzaga
The process usually takes about three to four hours, and they take about a can of Coke's worth of T cells, which is harmless 'cause your body creates T cells every day.

NARRATION
Matt's T cells were sent to the lab. They destroyed the CCR5 gene, and then sent them back to the clinic to be reinfused.

Grace Gonzaga
You're only giving a patient a small amount of modified T cells compared to the actual immune system that's creating their normal T cells. Ideally, we want a patient to have more of these modified T cells in their system so that their body has more of a chance to fight the virus on its own.

NARRATION
Even though Matt is still on his medications, he did see a resurgence of his T cells.

Matt Sharp
My T cells were almost doubled really over a very short time. I'd never seen that with any drug trial I'd been in before. And then over time, over the several months and years, that level stayed high, and so I knew I was having good results, yeah.

NARRATION
Eventually, they hope that the patient's newly modified T cells will be able to keep the level of virus under control without the need for medication.

Dr Maryanne Demasi
Using modified T cells has its limits because they have a finite lifespan. Researchers needed something that would act like a constant reservoir for these cells, so they turned to the stem cell.

Associate Professor Paula Cannon
Cool thing about stem cells is because they constantly make daughters that go on to grow up and some of them become T cells, if you go into an actual stem cell and make that CCR5-negative, you're gonna have a much bigger effect. They will continue, hopefully for the life of the patient, to keep making CCR5-negative progeny cells, including the T cells. So, in that way, we can also increase the frequency.

NARRATION
Professor Cannon was able to silence the CCR5 gene in the stem cells of mice. But these were no ordinary mice.

Associate Professor Paula Cannon
This is where we keep our humanised mice, as we call them. These mice are really special - they look just like regular, white mice but, actually, they have contained within them pretty much a whole human immune system.

Dr Maryanne Demasi
So this is necessary because HIV is a human virus...

Associate Professor Paula Cannon
Mm-hmm.

Dr Maryanne Demasi
..and it wouldn't infect mice.

Associate Professor Paula Cannon
Yes, HIV doesn't normally infect mice.

NARRATION
Half of the mice were transplanted with the newly modified stem cells, and the other half weren't.

Associate Professor Paula Cannon
It was actually really exciting to see because after about six weeks, the mice that had been modified to have lost some of the CCR5 protein, those mice started to control the HIV infection, and it started to go down. And by about three months, we basically couldn't find any HIV left in those mice. So they'd cured themselves of HIV.

Dr Maryanne Demasi
That's incredible! I mean, were you surprised by the results?

Associate Professor Paula Cannon
Yes.

Dr Maryanne Demasi
(Laughs) Excited?

Associate Professor Paula Cannon
Yes, very much so. We didn't exactly break out the...

NARRATION
Human trials with modified stem cells are already underway in the US and Australia. In the meantime, controlling the spread of HIV is paramount. The key to that is widespread testing.

Dr Maryanne Demasi
Here in the US, you can actually buy HIV tests at your local pharmacy.

NARRATION
The best thing about this is that you don't have to wait for lab tests. You can do it yourself and you can have the results in 20 minutes.

Dr Maryanne Demasi
Negative.

NARRATION
In Australia, a resurgence of HIV is of concern to advocacy organisations like ACON.

Nicholas Parkhill
In New South Wales, in 2012, we saw a 24% increase. 19% in gay men, 24% across the board. And that resurgence happening in New South Wales is happening in most other Australian States and indeed most other developed countries throughout the world.

NARRATION
It's thought to be because people no longer consider HIV a death sentence.

Voice-over in commercial
..that in three years, nearly 2,000 of us will be dead.

NARRATION
In the mid-'80s, Australia launched a series of fear campaigns.

Voice-over in commercial
..that if not stopped, it could kill more Australians than World War II.

Nicholas Parkhill
Some of the early campaigns in response to HIV were based around fear and scaring people, and that fear perhaps at that time perhaps motivated some people to change their sexual practices. What they also did though was create a level of stigma and discrimination for HIV-positive people. And that impact is still with us today.

Voice-over in commercial
Remember, we took up the fight, we raised awareness.

Nicholas Parkhill
It's more important that we talk about the importance of staying safe, the importance of getting tested and the importance of health benefits of treatment. So that's why our latest campaign, 'Ending HIV', really talks about those three elements.

NARRATION
As many as 10,000 people with HIV don't know they're infected. At this city-based centre in Sydney, they've introduced the rapid HIV screening test.

Nicholas Parkhill
What that allows people to do is go in for a test and have their results within 30 minutes.

NARRATION
It's free and it's as simple as going in and having the test done confidentially.

Nicholas Parkhill
Given that we know around 30% of people with HIV don't know that they're living with the virus, it's absolutely critical that people get tested so they know their status, so that they can take appropriate steps to modify their behaviour and also get the help, support and health care and treatment, if they're ready for it, that they need.

NARRATION
Researchers are excited about the potential of these new gene therapies. But, for now, HIV/AIDS still remains a life-threatening disease.

Dr Maryanne Demasi
The cocktail of drugs places a huge burden on the patient's health and the economy. That's why the hope for a cure still burns bright.

Matt Sharp
I would just love to see the place and the point in time where I can not have to take medications anymore, and maybe just find ways for my own body to control HIV without the medications. If we could get there, I would go to my grave happily, I guess.

Timothy Ray Brown
I'm planning on coming here as much as possible to lobby Congress for more funding for an HIV cure.

Dr Maryanne Demasi
Do you think it will happen in your lifetime?

Timothy Ray Brown
Yes, I do think it's going to happen in my lifetime.

STORY CONTACTS

Nicolas Parkhill 
CEO, AIDS Council of NSW 

Associate Professor Paula Cannon 
HIV Researcher
University of Southern California
USA

Professor Stephen O’Brien 
Genetiscst, HIV researcher
Harvard School of Public Health
USA

Timothy Ray Brown “The Berlin Patient” 
C/O Dave Purdy
Timothy Ray Brown Foundation of the World AIDS Institute
USA

Dr Gero Hutter 
Oncologist, HIV Researcher
Heidelberg University, 
Germany

Grace Gonzaga 
Quest Clinical Research nurse
San Francisco,USA