RAPID CURE FOR HIV
HIV-positive mothers who take antiretroviral therapies while
pregnant can be prevented from transmitting the virus to their babies
99% of the time — a resounding success story in the decades-long fight
against the virus. But what about infants whose mothers do not receive
the drugs? Energized by the case of the ‘Mississippi baby’ — who seemed
to be cured of HIV after aggressive treatment was begun within hours of
birth — researchers are hoping to show that these infants, too, can get
off to a healthy start.
At a symposium on HIV cure research on 29 June at the
International AIDS Society’s biennial meeting in Kuala Lumpur, Malaysia,
investigators will describe how they are racing to design a clinical
trial to test whether the early treatment works, and why. They hope to
treat the first babies by the end of this year.
The trial, sponsored by the International Maternal
Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Group, marks a
change for the field: so far, most research worldwide has focused on
adults. In 2012, the US National Institute of Allergy and Infectious
Diseases in Bethesda, Maryland, spent US$18 million on HIV cure research
in adults and adolescents, and just $45,000 on children. Yet
3.3 million children worldwide have HIV.
“Children
have been an afterthought,” says Jeffrey Safrit, director of clinical
and basic research for the Elizabeth Glaser Pediatric AIDS Foundation,
who is based in Los Angeles, California. “But the immune system of the
child might be more easily manipulated to allow a cure.”
This was highlighted in March, when virologist Deborah
Persaud of the Johns Hopkins Children’s Center in Baltimore, Maryland,
announced that a baby in Mississippi who received treatment for HIV
within 31 hours of birth stopped medication at 18 months without the
virus rebounding (see
Nature http://doi.org/m2d; 2013).
Researchers knew that early treatment could help infants to control
HIV, but were surprised that they could essentially wipe it out from an
infant’s body using existing drugs.
Early HIV treatment is helpful for patients of any age. It
stops the virus from replicating before it can infect central memory
T cells, the main immune-cell reservoir where HIV ‘hides’ from drugs.
But researchers think that babies are better targets for HIV cures than
adults because of their immature immune systems, which respond more
mildly when provoked. Because the cells involved in this ‘inflammatory
response’ are the same ones that are most susceptible to HIV, this could
mean that infants are less prone to the infection spreading. Moreover,
babies are born without central memory T cells, so they are likely to
have a smaller reservoir of infected cells, says Mike McCune, an
immunologist at the University of California, San Francisco.
The IMPAACT study, to be conducted across some of the
group’s 71 sites worldwide, will screen and treat hundreds of babies to
find 20–30 infants who have acquired HIV from untreated mothers or from
those whose HIV was not well controlled during pregnancy. Because
diagnosing HIV takes up to 7 days, all screened babies will
automatically receive a similar treatment to the Mississippi baby: a
cocktail of three drugs within 48 hours of birth. Physicians will add a
fourth drug if babies then test positive for HIV. Around the age of
three, the 20–30 children will be tested to see whether their immune
systems make antibodies to HIV or if it can be detected in their blood.
Those testing negative on both counts would then be taken off the drugs
to see whether they can remain HIV-free.
The practical and ethical challenges of the trial are
significant. Babies of untreated HIV-positive women have only a 15–30%
chance of infection at birth, so the trial will need to recruit many
babies to try to cure the few who are infected. Those who do not
contract HIV will be treated anyway, perhaps exposing them to drug side
effects. These are usually mild, but can deplete certain blood cells.
But children born to untreated HIV-positive women are
already given up to three drugs after birth as a precaution. The
potential for finding a cure far outweighs the risks of adding another
drug, or of stopping treatment to test whether the cure has worked, says
Yvonne Bryson, a physician at the Mattel Children’s Hospital at the
University of California, Los Angeles, and co-chair of the trial.
“There’s much more benefit to be gained than risk,” she says.
Physicians are already considering changing the way they
treat children infected by the virus. Bryson says that families of
HIV-positive teenagers who were treated soon after birth and kept on
medication are now asking that the teens be taken off the drugs.
Ultimately, the 34 million people worldwide who live with
HIV could also benefit, researchers say. If it turns out that infants
are more amenable to cures because they have a less active inflammatory
response, that might encourage physicians to prescribe treatments that
are less likely to trigger inflammation in adults, McCune says.
Bryson, who has worked on HIV since the first case was
detected, thinks that the end could be in sight. “I saw patient zero,”
Bryson says. “I’ve always been so excited to think that I would see the
day that we would arrive at a cure, and I think we’re here.”
