The surprise success now confirms
that a cure for HIV infection is possible, if difficult, researchers said.
For
just the second time since the global epidemic began, a patient appears to have
been cured of infection with HIV, the virus that causes AIDS.
The
news comes nearly 12 years to the day after the first patient known to be
cured, a feat that researchers have long tried, and failed, to duplicate. The
surprise success now confirms that a cure for HIV infection is possible, if
difficult, researchers said.
The
investigators are to publish their report Tuesday in the journal Nature and to
present some of the details at the Conference on Retroviruses and Opportunistic
Infections in Seattle.
Publicly,
the scientists are describing the case as a long-term “remission.” In
interviews, most experts are calling it a cure, with the caveat that it is hard
to know how to define the word when there are only two known instances.
Both
milestones resulted from bone-marrow transplants given to infected patients.
But the transplants were intended to treat cancer in the patients, not HIV.
Bone-marrow
transplantation is unlikely to be a realistic treatment option in the near
future. Powerful drugs are now available to control HIV infection, while the
transplants are risky, with harsh side effects that can last for years.
But
rearming the body with immune cells similarly modified to resist HIV might well
succeed as a practical treatment, experts said.
“This
will inspire people that cure is not a dream,” said Dr. Annemarie Wensing, a
virologist at the University Medical Center Utrecht in the Netherlands. “It’s
reachable.”
Wensing
is co-leader of IciStem, a consortium of European scientists studying stem cell
transplants to treat HIV infection. The consortium is supported by AMFAR, the
American AIDS research organization.
The
new patient has chosen to remain anonymous, and the scientists referred to him
only as the “London patient.”
“I
feel a sense of responsibility to help the doctors understand how it happened
so they can develop the science,” he told The New York Times in an email.
Learning
that he could be cured of both cancer and HIV infection was “surreal” and
“overwhelming,” he added. “I never thought that there would be a cure during my
lifetime.”
At
the same conference in 2007, a German doctor described the first such cure in
the “Berlin patient,” later identified as Timothy Ray Brown, 52, who now lives
in Palm Springs, California.
That
news, displayed on a poster at the back of a conference room, initially gained
little attention. Once it became clear that Brown was cured, scientists set out
to duplicate his result with other cancer patients infected with HIV.
In
case after case, the virus came roaring back, often around nine months after
the patients stopped taking antiretroviral drugs, or else the patients died of
cancer. The failures left scientists wondering whether Brown’s cure would
remain a fluke.
Brown
had leukemia, and after chemotherapy failed to stop it, needed two bone-marrow
transplants.
The
transplants were from a donor with a mutation in a protein called CCR5, which
rests on the surface of certain immune cells. HIV uses the protein to enter
those cells but cannot latch on to the mutated version.
Brown
was given harsh immunosuppressive drugs of a kind that are no longer used, and
suffered intense complications for months after the transplant. He was placed
in an induced coma at one point and nearly died.
“He
was really beaten up by the whole procedure,” said Dr. Steven Deeks, an AIDS
expert at the University of California, San Francisco, who has treated Brown.
“And so we’ve always wondered whether all that conditioning, a massive amount
of destruction to his immune system, explained why Timothy was cured but no one
else.”
The
London patient has answered that question: A near-death experience is not
required for the procedure to work.
He
had Hodgkin lymphoma and received a bone-marrow transplant from a donor with
the CCR5 mutation in May 2016. He, too, received immunosuppressive drugs, but
the treatment was much less intense, in line with current standards for
transplant patients.
He
quit taking anti-HIV drugs in September 2017, making him the first patient
since Brown known to remain virus-free for more than a year after stopping.
“I
think this does change the game a little bit,” said Dr. Ravindra Gupta, a
virologist at University College London who presented the findings at the
Seattle meeting. “Everybody believed after the Berlin patient that you needed
to nearly die basically to cure HIV, but now maybe you don’t.”
Although
the London patient was not as ill as Brown had been after the transplant, the
procedure worked about as well: The transplant destroyed the cancer without harmful
side effects. The transplanted immune cells, now resistant to HIV, seem to have
fully replaced his vulnerable cells.
Most
people with the HIV-resistant mutation, called delta 32, are of Northern
European descent. IciStem maintains a database of about 22,000 such donors.
So
far, its scientists are tracking 38 HIV-infected people who have received
bone-marrow transplants, including six from donors without the mutation.
The
London patient is 36 on this list. Another one, number 19 on the list and
referred to as the “Düsseldorf patient,” has been off anti-HIV drugs for four
months. Details of that case will be presented at the Seattle conference later
this week.
The
consortium’s scientists have repeatedly analyzed the London patient’s blood for
signs of the virus. They saw a weak indication of continued infection in one of
24 tests, but say this may be the result of contamination in the sample.
The
most sensitive test did not find any circulating virus. Antibodies to HIV were
still present in his blood, but their levels declined over time, in a
trajectory similar to that seen in Brown.
None
of this guarantees that the London patient is forever out of the woods, but the
similarities to Brown’s recovery offer reason for optimism, Gupta said.
“In
a way, the only person to compare with directly is the Berlin patient,” he
said. “That’s kind of the only standard we have at the moment.”
Most
experts who know the details agree that the new case seems like a legitimate
cure, but some are uncertain of its relevance for AIDS treatment overall.
“I’m
not sure what this tells us,” said Dr. Anthony Fauci, director of the National
Institute of Allergy and Infectious Diseases. “It was done with Timothy Ray
Brown, and now here’s another case — ok, so now what? Now where do we go with
it?”
One
possibility, said Deeks and others, is to develop gene-therapy approaches to
knock out CCR5 on immune cells or their predecessor stem cells. Resistant to
HIV infection, these modified cells should eventually clear the body of the
virus.
(CCR5
is the protein that He Jiankui, a scientist in China, claimed to have modified
with gene editing in at least two children, in an attempt to make them
resistant to HIV — an experiment that set off international condemnation.)
Several
companies are pursuing gene therapies but have not yet been successful. The
modification must target the right number of cells, in the right place — only
the bone marrow, for example, and not the brain — and tweak only the genes
directing production of CCR5.
“There
are a number of levels of precision that must be reached,” said Dr. Mike
McCune, a senior adviser on global health to the Bill and Melinda Gates
Foundation. “There are also concerns that you might do something untoward, and
if so you might wish to have a kill switch.”
Several
teams are working on all of these obstacles, McCune said. Eventually, they may
be able to develop a viral delivery system that, when injected into the body,
seeks out all CCR5 receptors and deletes them, or even a donor stem cell that
is resistant to HIV but could be given to any patient.
“These
are dreams, right? Things on the drawing table,” McCune said. “These dreams are
motivated by cases like this — it helps us to imagine what might be done in the
future.”
One
important caveat to any such approach is that the patient would still be
vulnerable to a form of HIV called X4, which employs a different protein,
CXCR4, to enter cells.
“This
is only going to work if someone has a virus that really only uses CCR5 for
entry — and that’s actually probably about 50 percent of the people who are
living with HIV, if not less,” said Dr. Timothy J. Henrich, an AIDS specialist
at the University of California, San Francisco.
Even
if a person harbors only a small number of X4 viruses, they may multiply in the
absence of competition from their viral cousins. There is at least one reported
case of an individual who got a transplant from a delta 32 donor but later
rebounded with the X4 virus. (As a precaution against X4, Brown is taking a
daily pill to prevent HIV infection.)
Brown
says he is hopeful that the London patient’s cure proves as durable as his own.
“If something has happened once in medical science, it can happen again,” Brown
said. “I’ve been waiting for company for a long time.”
Source:THE INDIAN EXPRESS-6th March,2019
