Timothy Brown T.J. Kirkpatrick / Getty Images
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.
Posted on Jul. 20, 2016, at 11:42 a.m.
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.
A rhesus macaque monkey Ed Jones / AFP / Getty Images
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.”
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