How did a transplant cure this man of HIV?

Researchers have come closer than ever to understanding how a man was cured of HIV almost 10 years ago.

Timothy Brown, the 51-year-old American man known as the ‘Berlin patient’, was declared HIV-free in 2008 after two bone marrow transplants at a hospital in Berlin.

He is one of just two people in history (and the first identified) to successfully beat the virus, and all attempts to replicate his procedure have ended in death.

However, a team at Oregon Health And Science University today published a paper on an ongoing study on a specific insular breed of monkey, which appears to be our strongest bet at replicating and understanding the mysterious case.

While the researchers say they believe completely curing HIV is unlikely to ever happen, they say Brown’s bone marrow procedure, if refined, could help patients reach ‘drug-free remission’.

Speaking to Daily Mail Online, Brown said he is ‘very excited’ about the study, which he has been following closely with regular updates from lead author Dr Jonah Sacha.

‘I would love to know what cured me,’ said Brown, who spends his year speaking at conferences, attending HIV presentations, and advocating for new research.

Mystery: Timothy Brown, now 51, (pictured in 2012) is the Seattle-born man known as the 'Berlin patient'. He was declared HIV-free in 2008 after two bone marrow transplants at a hospital in Berlin

Mystery: Timothy Brown, now 51, (pictured in 2012) is the Seattle-born man known as the ‘Berlin patient’. He was declared HIV-free in 2008 after two bone marrow transplants at a hospital in Berlin

‘From the moment I got cured, I had the option to hide my identity. But I wanted people to know, I don’t want to be the only person who was cured.’

Brown, who is from Seattle but lived in Germany, was diagnosed with HIV in 1995.

In 2006, after more than a decade on standard anti-retroviral therapy to suppress his disease, he was diagnosed with acute myeloid leukemia, a cancer of the blood cells.

His doctor at the Charite Hospital in Berlin said his best bet at survival was a bone marrow transplant, which replaces a sick person’s immune system with stem cells from the bone marrow of a healthy person.

It is an incredibly delicate and risky procedure, since one’s immune system is designed to defend their own body against foreign cells or pathogens.

There is a risk of death if it is not a strong enough match. Instead of seamlessly replacing one weakened immune system with the other, the transplant could trigger a battle between the two immune systems, killing the patient.

According to Be The Match, the chance of finding a perfect match is about 50/50, but even then there is a risk.

Finding a precise match for someone with HIV is even more complex, since their immune system is already compromised.

In Brown’s case, he received a transplant from a person with a mutation of the CCR5 receptor, which has been linked to HIV immunity.

Despite the risks, Brown survived his first transplant, and stopped taking his HIV medication that day. He had another transplant in early 2008. On February 2008, he was declared HIV-free at the CROI Conference in Boston.

The only other person to have been cured of HIV remains anonymous. He was also in Berlin, and was declared HIV-free in 1998 after being prescribed an unconventional cocktail of HIV and cancer drugs.

Studies have since shown that the 1998 case appears to have largely been influenced by the patient’s genes.

But Brown’s case remains a mystery — and attempts to replicate his transplant have been disastrous.

Indeed, 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.

Consequently, researchers require an animal model to investigate.
Scientists at Oregon Health and Science University have successfully performed the transplant on Mauritian cynomolgus macaque monkeys, who are all very genetically similar

While bone marrow transplants have been shown to work in rhesus monkeys, a common species in scientific experiments, they are too genetically diverse to be a reliable model. In fact, many of the failed attempts at curing HIV in patients with bone marrow have been linked to some of the proteins found in rhesus monkeys’ immune systems.

Instead, Oregonian researchers have turned to examining a specific group of monkeys descended from just five monkeys left on an island by Dutch spice traders five centuries ago.

Cynomolgus macaques, also known as crab-eating or long-tailed macaques, are prevalent across south-east Asia.

But in Mauritius, the Indian Ocean island off the coast of Madagascar, there is a population of them who descended from just five monkeys, left on the island in the early 1500s.

At the time, there were just four males and one female. As such, today’s population is not very genetically-diverse, and the chance of finding a bone marrow match is high.

In a new report published early Friday morning, the researchers from the university’s Vaccine and Gene Therapy Institute declared they successfully performed a stem cell transplant in two of these monkeys, who are healthy more than a year later.

The team, led by Dr Sacha, said the promising finding could take about a decade to develop into a functional treatment, but it also sheds light on how we could use stem-cell transplants for other diseases like leukemia and sickle cell anemia.

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