Scientists hoping to cure HIV have proven that an immunotherapy drug is safe to use in humans.
The phase 1 trial is an early but significant milestone for the team at the University of North Carolina at Chapel Hill, which won a $20 million grant to make their ideas a reality.
In the last couple of years immunotherapy, which trains a person’s immune system to attack a disease, became mainstream, and is now being used to treat scores of conditions, from cancer to blindness.
However, scientists are treading lightly when it comes to HIV, because attempts in the last 20 years to cure the virus with bone marrow transplants (another mainstream treatment which replaces a person’s immune system with that of a donor) have proved fatal in all but one person.
For the first time, in a study published today by the journal Cell Reports, the North Carolina team has confirmed their hopes: that immunotherapy could be administered to HIV positive patients without a realistic risk of death – and many are tipping it as proof that this could be it.
‘We think that we will be able to replicate the results of the Berlin patient [the only person ever cured of HIV], but that will take a while, on a step-by-step trajectory,’ Dr David Margolis, co-senior author of the new paper.
The phase 1 trial is an early but significant milestone for the team at the University of North Carolina at Chapel Hill, which won a $20 million grant to make their ideas a reality
THE ONLY CURE THAT EVER WORKED – AND WHY IT NEVER WORKED AGAIN
The only person ever cured of HIV is an American man called Timothy Brown, widely known as ‘the Berlin patient’ because he was cured in Berlin in 2007.
Brown already had HIV when he was diagnosed with leukemia, a disease of the bone marrow which can be treated with a bone marrow transplant.
Bone marrow transplants are usually the last resort because there is a significant risk of death, by triggering a war between the person’s original immune system and the new implanted one.
But Brown didn’t have many other options. Once he agreed, his doctor suggested trying to select a donor who had genes known to be resistant to HIV. At the time it was more of an attempt to protect him, rather than cure him.
Not only did Brown survive the operation, and survive free of leukemia, he also had no trace of the human immunodeficiency virus.
The news rocked the medical community, with speculation that this could be the end of HIV/AIDS.
However, attempts to replicate it were devastating.
A report published by the New England Journal of Medicine in 2014 described six attempts to treat HIV patients with a stem cell donation, but none lived longer than a year.
CURRENT ATTEMPTS TO FIND A WORKING CURE FOR EVERYBODY
More than 10 years on, we’re still ‘very far off’ replicating the case of the Berlin patient, according to Dr Margolis, though the attempts to do so are by no means few.
These days, HIV positive patients are prescribed anti-retroviral therapy (ART), which is now so effective that it can suppress the virus within six months – to such an extent that it is deemed undetectable and untransmittable. (It is important to note that becoming undetectable requires the person to take the drug consistently, and staying undetectable requires keeping up their regimen.)
ART, and PrEP (pre-exposure prophylaxis, a pill which protects a person from contracting HIV), have been game changers in the fight against HIV/AIDS, drastically cutting the rate of new infections, and turning HIV from a death sentence to a life-long chronic illness.
However, the one thing that no one can get at is the elusive phenomenon of latent HIV: strands of the virus which lie hidden and dormant in ‘reservoirs’ of the body, evading treatment.
One team, at Oregon Health And Science University, is tackling this problem by trying to zero in on the Berlin patient’s cure. To do so, they are testing it on a specific group of monkeys descended from just five monkeys left on an island near Mauritius by Dutch spice traders five centuries ago, making them so genetically concentrated that it’s easier to understand how the transplants affect them.
The team expects it will take more than 10 years to reach some tangible, applicable conclusions that could be replicated in humans.
Meanwhile Dr Margolis, his co-senior author Catherine Bollard of the Children’s National Health System, and their team are taking a different tact, looking at the treatment of the moment, immunotherapy.
With the $4 million-a-year backing of GlaxoSmithKline, their research team is conducting two concurrent studies.
This phase 1 trial is the first to be published. The aim was to prove that the immune system could be trained to attack HIV, without sparking an internal civil war between cells that could kill the patient in the process.
It was a small study, testing the method on six patients. It involved extracting T cells (a lymphocyte crucial to the immune system), growing them in the lab so they multiply, then injecting them back in so they can go into overdrive attacking the virus inside.
All of the patients in this study had been on ART for an average of six years. They didn’t see any significant benefits, but that wasn’t the point. The point was to check that it didn’t hurt anyone.
Ultimately, the plan is to first administer a therapy that would bring out the HIV from hiding, before unleashing the T cells.
The method has been colloquially dubbed the ‘shock and kill’ technique, though it’s a term Dr Margolis takes issue with (‘it makes it sound A. very easy, and B. scary’).
‘This is a promising advancement for the field,’ says first author Julia Sung of UNC, although she also cautions people against over-interpreting the results. ‘The study did not cure HIV and should not be interpreted as doing so, but we also are very encouraged by the safety data, so it should not be considered discouraging either. This paves the way for the next step.’