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Chicago: A baby girl in Mississippi who was
born with HIV has been cured after very early treatment with
standard HIV drugs, US researchers reported yesterday, in a
potentially ground-breaking case that could offer insights on how
to eradicate HIV infection in its youngest victims.
The child's story is the first account of an infant achieving a
so-called functional cure, a rare event in which a person achieves
remission without the need for drugs and standard blood tests show
no signs that the virus is making copies of itself.
More testing
needs to be done to see if the treatment would have the same
effect on other children, but the results could change the way
high-risk babies are treated and possibly lead to a cure for
children with HIV, the virus that causes AIDS.
"This is a proof of
concept that HIV can be potentially curable in infants," said Dr.
Deborah Persaud, a virologist at Johns Hopkins University in
Baltimore, who presented the findings at the Conference on
Retroviruses and Opportunistic Infections in Atlanta.
The child's story is different from the now famous case of Timothy
Ray Brown, the so-called "Berlin patient," whose HIV infection was
completely eradicated through an elaborate treatment for leukemia
in 2007 that involved the destruction of his immune system and a
stem cell transplant from a donor with a rare genetic mutation
that resists HIV infection.
"We believe this is our Timothy Brown
case to spur research interest toward a cure for HIV infection in
children," Persaud said at a news conference.
Instead of Brown's costly treatment, however, the case of the
Mississippi baby, who was not identified, involved the use of a
cocktail of widely available drugs already used to treat HIV
infection in infants.
When the baby girl was born in a rural
hospital in July 2010, her mother had just tested positive for HIV
infection. Because her mother had not received any prenatal HIV
treatment, doctors knew the child was at high risk of infection.
They transferred her to the University of Mississippi Medical Center in Jackson, where she came under the care of Dr Hannah Gay,
a pediatric HIV specialist. Because of her risk, Dr Gay put the
infant on a cocktail of three HIV-fighting drugs - zidovudine
(also known as AZT), lamivudine, and nevirapine - when she was
just 30 hours old.
Two blood tests done within the first 48 hours
of the child's life confirmed her infection and she was kept on
the full treatment regimen, Persaud told reporters at the
conference.
In more typical pregnancies, when an HIV-infected mother has been
given drugs to reduce the risk of transmission to her child, the
baby would only have been given a single drug, nevirapine.
Researchers believe use of the more
aggressive antiretroviral treatment when the child was just days
old likely resulted in her cure by keeping the virus from forming
hard-to-treat pools of cells known as viral reservoirs, which lie
dormant and out of the reach of standard medications.
These reservoirs rekindle HIV
infection in patients who stop therapy, and they are the reason
most HIV-infected individuals need lifelong treatment to keep the
infection at bay.
After starting on treatment, the baby's immune system responded
and tests showed diminishing levels of the virus until it was
undetectable 29 days after birth.
The baby received regular treatment
for 18 months, but then stopped coming to appointments for a
period of about 10 months, when her mother said she was not given
any treatment.
The doctors did not say why the
mother stopped coming. When the child came back under the care of
Dr Gay, she ordered standard blood tests to see how the child was
faring before resuming antiviral therapy.
What she found was surprising. The first blood test did not turn
up any detectible levels of HIV. Neither did the second. And tests
for HIV-specific antibodies, the standard clinical indicator of
HIV infection, also remained negative.
"At that point, I knew I
was dealing with a very unusual case," Dr Gay said.
Baffled, Dr
Gay turned to her friend and longtime colleague, Dr Katherine
Luzuriaga of the University of Massachusetts, and she and Persaud
did a series of sophisticated lab tests on the child's blood.
The
first looked for silent reservoirs of the virus where it remains
dormant but can replicate if activated. That is detected in a type
of immune cell known as a CD4 T-cell.
After culturing the child's cells,
they found no sign of the virus. Then, the team looked for HIV
DNA, which indicates that the virus has integrated itself into the
genetic material of the infected person.
This test turned up such low levels
that it was just above the limit of the test's ability to detect
it. The third test looked for bits of genetic material known as
viral RNA. They only found a single copy of viral RNA in one of
the two tests they ran.
Because there is no detectible virus in the child's blood, the
team has advised that she not be given antiretroviral therapy,
whose goal is to block the virus from replicating in the blood.
Instead, she will be monitored closely. There are no samples that
can be used by other researchers to confirm the findings, which
may lead skeptics to challenge how the doctors know for sure that
the child was infected.
Persaud said the team is trying to
use the tiny scraps of viral genetic material they have been able
to gather from the child to compare with the mother's infection,
to confirm that the child's infection came from her mother.
But, she stressed, the baby had
tested positive in two separate blood tests, and there had been
evidence of the virus replicating in her blood, which are standard
methods of confirming HIV infection.
Dr Anthony Fauci, director of the National Institutes of Allergy
and Infectious Diseases, said although tools to prevent
transmission of HIV to infants are available, many children are
born infected.
"With this case, it appears we may have not only a
positive outcome for the particular child, but also a promising
lead for additional research toward curing other children," he
said.
Dr Rowena Johnston, vice president and director of research
for amfAR, The Foundation for AIDS Research, which helped fund the
study, said the fact that the cure was achieved by antiretroviral
therapy alone makes it "imperative that we learn more about a
newborn's immune system, how it differs from an adult's and what
factors made it possible for the child to be cured."
Because the
child's treatment was stopped, the doctors were able to determine
that this child had been cured, raising questions about whether
other children who received early treatment and have undetectable
viral loads may also be cured without their doctors knowing it.
But the doctors warned parents not to be tempted to take their
children off treatment to see if the virus comes back. Normally,
when patients stop taking their medications, the virus comes
roaring back, and treatment interruptions increase the risk that
the virus will develop drug resistance. "We don't want that," Dr
Gay said.
"Patients who are on successful therapy need to stay on
their successful therapy until we figure out a whole lot more
about what was going on with this child and what we can do for
others in the future."
The researchers are trying to find
biomarkers that would offer a rationale to consider stopping
therapy within the context of a clinical trial. If they can learn
what caused the child to clear her virus, they hope to replicate
that in other babies, and eventually learn to routinely cure
infections.
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