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Only One Person Has Been Cured Of AIDS — Can We Do It Again?

Results announced at the International AIDS Conference this week aim to recreate the success of Timothy Brown, the only man in the world to be cured of AIDS.

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In 2007, a man with AIDS in Germany began the first of two bone marrow transplants he desperately needed to treat a rare form of blood cancer that threatened to kill him. The procedures were risky — his doctor needed to find an exact marrow match so that the donor cells would not destroy his own. But his doctor in Berlin decided to make this search even harder: He wanted to find a donor whose DNA might be protected from HIV.

About a decade earlier, scientists had discovered a rare DNA mutation that prevented the HIV virus from infecting blood cells. The small group of people known to carry the mutation were naturally resistant to HIV, and the doctor thought that maybe, if his patient’s new bone marrow had the same mutation, then he could be free of AIDS, too.

The man, initially known as the Berlin Patient, did get a transplant with the special mutation, and stopped taking his antiretroviral medications. In 2008, his doctors announced that, even without these drugs, he had no detectable levels of HIV. Now known to be a Seattle native named Timothy Brown, the man is still free of the virus today, and the only person ever to be cured of HIV.

Over the past eight years, scientists have tried many ways to replicate what happened in Timothy Brown’s body. On Thursday at the massive International AIDS Conference in Durban, South Africa, a group of European researchers will report that they may have done so in two people with the disease. Since getting bone marrow transplants three years ago, these two patients have cleared HIV from their bodies (though they are also still taking antiretroviral drugs).

Since its launch in 2012, the study, known as the EpiStem project, has given bone marrow transplants to 15 people with HIV and severe cancer (all of whom would have gotten the transplants anyway). Of those, nine died from complications related to the extremely risky procedure. Results on the three who have passed the three-year mark are being presented at the conference. Two of them carry no HIV in their blood, and the third has very low levels of the virus.

“We see a huge decrease of the viral reservoir,” Annemarie Wensing, a clinical virologist at the University Medical Center Utrecht and one of the leaders of the EpiStem study, told BuzzFeed News. “That’s not seen with any of the other cure strategies in clinical trials.”

But others are asking whether this approach is too dangerous to be used on the vast majority of people carrying HIV.

“They got lucky in terms of Timothy Brown — he was able to survive not one but two transplants, and come out alive,” Carl Dieffenbach, head of the Division of AIDS at the National Institutes of Allergy and Infectious Diseases, told BuzzFeed News.

“You have to remember that purpose of a physician is to first do no harm,” Dieffenbach added. “I think where we are right now is, how can we take this and consider it as potentially going beyond people with these life threatening diseases?”

To find bone marrow transplant donors who carry the HIV-resistant mutation — which affects a cell receptor known as CCR5 — the researchers sequenced the DNA of more than 1,000,000 potential donors in Europe.

Some of the patients received transplants with the mutation, and others did not. By comparing these two groups, the researchers wanted to see whether Brown’s cure was the result of the CCR5 mutation, or of simply getting infused with foreign cells. (Bone marrow transplants often come with “graft-versus-host disease,” which kills off the body’s native cells and, some speculate, could be involved in wiping out HIV.)

The trial’s initial results are encouraging, Wensing said, though it’s still unclear whether the results are due to the CCR5-altered cells, the bone marrow transplant itself, or the standard antiretroviral medications.

Of the three individuals who have made it three years since their transplants, two received normal bone marrow cells and one received the HIV-resistant type. One of the individuals who received the normal type cells luckily avoided graft-versus-host disease. The other two — one of whom had HIV-resistant cells, and one of whom didn’t — did experience graft-versus-host. Both of these individuals now have undetectable levels of their own immune cells in their blood, but also have undetectable levels of HIV. The other patient has low levels of their own immune cells and HIV still detectable in their blood.

It will take some work to determine how the various factors are at play, but Wensing says the worst is over since the three patients are healthy and cancer-free. The next step will be deciding whether the patients will go off their antiretroviral medications, to see whether the bone marrow transplants were solely responsible for eradicating their HIV.

The researchers did not present any results from the other three patients in the trial, who got their transplants less than three years ago.

Meanwhile, on Sunday at the Durban conference, scientists from the Fred Hutchinson Cancer Center in Seattle reported on another promising approach to replicating Timothy Brown’s success.

The scientists took blood from monkeys infected with the monkey version of HIV (known as SHIV) and genetically engineered their stem cells to remove CCR5. They then infused the tweaked cells back into the animals, and took them off of their antiretroviral drugs.

The idea is that this approach, if successful, would remove the often lethal threat of graft-versus-host disease.

“The biggest thing that’s important about our approach is that we’re putting an animal’s own cells back into their bodies,” Chris Peterson, a staff scientist at Fred Hutchinson and leader of the study, told BuzzFeed News. “Now the question is, how well do they protect against infection?”

Their initial results showed that the genetically engineered blood cells preferentially grow when the virus is introduced into the monkeys — presumably because the virus is killing off all of the non-engineered cells.

The researchers also found that the tweaked cells spread everywhere — not just in the blood — and especially in hard-to-reach locations known to act as “reservoirs” for HIV, such as the gastrointestinal tract, the brain, and the lungs. It’s still too early to tell, however, whether these engineered blood cells are actually curbing HIV levels in the animals.

Other groups, including the California companies Sangamo Biosciences and Calimmune, are trying similar gene-editing approaches in people.

As for Timothy Brown, the scientists leading the new studies say he is aware of their efforts at replicating his success.

“We have spoken to him, he was very happy with the program,” Wensing said. “I think it’s lonely to be the only patient cured.”


Azeen Ghorayshi is a science reporter for BuzzFeed News and is based in New York. Her PGP Fingerprint is 9739 9DAE 607E A66A 3683 AC20 E34B D2A0 8899 74C4

Contact Azeen Ghorayshi at azeen.ghorayshi@buzzfeed.com.

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