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Second Baby Cleared Of HIV. Rare Event, Or Hope For Others?

03.04.2014 09:47

 

Second Baby Cleared Of HIV. Rare Event, Or Hope For Others?
by LINDA POON
March 06, 2014 4:00 PM ET
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In only the second documented case of its kind, an infant born with the AIDS virus may have been cured of the infection, thanks to an intensive drug treatment begun just hours after her birth. The baby girl — now 9 months old — from Long Beach, Calif., is still on that regimen of antiretroviral drugs. But researchers who described her case at an AIDS meeting in Boston this week say advanced testing suggests that she is HIV-negative.
 
While not conclusive, the two cases are "quite promising," says Anthony Fauci, a longtime AIDS researcher who directs the National Institute of Allergy and Infectious Diseases.
While not conclusive, the two cases are "quite promising," says Anthony Fauci, a longtime AIDS researcher who directs the National Institute of Allergy and Infectious Diseases.
 
Alex Wong/Getty Images
The California child's case comes three years after doctors apparently cleared an infant in Mississippi of her HIV infection shortly after she was born. That child is now a healthy 3-year-old who seems to be free of HIV, doctors say, despite having been off the AIDS drugs for almost two years now.
 
Researchers are eager to determine if the two remarkable cases are rare experiences or a broader sign of hope for the hundreds of HIV-infected babies born each day. To find out, clinical trials involving roughly 60 newborns will begin as early as this April or May, says Dr. Anthony Fauci, who directs the National Institute of Allergy and Infectious Diseases.
 
Fauci, whose institute funded the research in both cases, sat down on Thursday with NPR's Audie Cornish, for All Things Considered, to talk about the two children, and what their promising experience might mean for the future. Here's an edited excerpt of their conversation:
 
How is this course of treatment different from what's usually given to babies infected with HIV?
 
In the usual situation when a baby is born to an infected mother, you don't know at birth, for sure, if the baby is infected. So what you do is you give the baby what's called a preventive type of drug [regimen] — lower dose and [fewer drugs]. When you find out that the baby is ultimately infected, you switch over to the full component of three drugs at the right dose, to start treating them. ... The original Mississippi baby and the baby from California were treated within hours of birth as if they were infected. So instead of giving them the prevention type of drug over a period of a few weeks, they were immediately given the full-blown course of the treatment drugs.
 
But how did doctors know when to stop treatment in the first case — the little girl born in Mississippi?
 
Daily medications for young children with HIV include both tablets and liquid drugs in syringes.
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The doctors would never have just ... stopped drug [treatment] in the baby after several months. The mother was lost to follow up and [she apparently] stopped giving the drug to the baby. And then when [the mother and child] came back, the physician noticed that [the little girl] had been several months off therapy and the virus did not rebound. So a quirk — of the mother's decision, or accident, in not following up with the baby — has actually led to a situation that turned out to be beneficial.
 
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So that case was accidental. How will doctors know in the future when to stop drug treatment, and is that even ethical?
 
To just ... stop would not be ethical, and that's the reason why we're sponsoring a clinical trial that will begin sometime at the end of April [or] at the beginning of May, where we're taking a large number of babies ... born of mothers who are infected, [women] who have not received any [anti-HIV] treatment [during pregnancy] at all, and we're going to be treating those babies literally within 48 hours of birth with the full component of the treatment regimen. [We will be] assuming that they are infected, even though they might not be. And then we'll wait for a considerable period of time, and very carefully, in individual babies, stop therapy to see if the virus rebounds.
 
Lucrecia Silva and her daughter, Helena, are both HIV-positive. They wait as a nurse in Macia writes a prescription for Helena's anti-retroviral drugs.
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Give us some context. Just how big a problem is it — babies born HIV-positive?
 
In the United States, it's really not a big problem at all only because we have the [prenatal and postnatal] care for the mothers, and almost all mothers who are infected will be started on [antiretroviral drug] therapy. It will be extremely unlikely that the baby will be infected – not impossible but very, very unlikely. However, the situation in the developing world is somewhat different. [There] it's not uncommon that a mother will come into a clinic, in labor, ready to deliver, never having seen a health care provider, and not being on antiviral therapy. Those are the babies that are at the highest risk.
 
How promising are these findings?
 
Well, it's quite promising because if it's the second one that we have documented now — and there probably will be others coming along — it really brings up a broader concept. If you have the possibility of truly curing babies at the time of birth, then the risk/benefit ratio of waiting until you document that they're infected ... that really changes the equation.
 
 
 
 
 
 
 
 
Monkeys expose narrow window for baby HIV 'cure'

A second baby has been cleared of HIV, almost a year after a similar case with a baby in Mississippi was announced. The second baby, who was treated in California, is still being given anti-HIV drugs, but blood tests can no longer identify virus particles capable of replicating. Both infants were given antiretroviral drugs almost immediately after birth.

Work in monkeys, also presented at the Conference on Retroviruses and Opportunistic Infections in Boston, suggests that the window for successful early intervention is narrow – a delay of just three days made a huge difference in the way the monkeys responded to treatment.

Usually, newborn babies with suspected HIV infections from their mothers are not treated until weeks after birth when infection has been confirmed. Audra Deveikis of the Miller Children's Hospital in Long Beach, California, gave the baby antiretroviral therapy four hours after birth because her mother, who has advanced AIDS, had not taken the antiretroviral drugs she had been given.

Later tests on spinal fluid confirmed that the California baby – now 9 months old – had indeed been infected.

Speedy treatment

This isn't the first time early intervention has paid off. The Mississippi baby was given drugs 30 hours after birth. Two years later, and 10 months after stopping drug treatment, there were no detectable signs of the virus and no HIV antibodies in her blood. The child is now more than three years old and remains virus-free, Deborah Persaud of the Johns Hopkins Children's Center, Maryland, who has run tests on both infants, told the meeting yesterday.

Also last year, it was announced that the "Visconti group" of 14 adults who received treatment between 35 days and 10 weeks after infection – much earlier than usual – were also virus-free after an average of seven years without medication.

Research in rhesus macaques shows why early treatment is critical to keeping the virus under control. Although the experiment involved SIV, the monkey equivalent of HIV, the results are likely to apply to the human form, say the researchers.

Afam Okoye of the Oregon National Primate Research Center in Beaverton, Oregon, and his colleagues injected 22 macaques with SIV and divided them into three groups according to their speed of treatment. The first two monkeys received antiretroviral therapy seven days after infection, the second two 10 days after, and the final 18 at 42 days later.

In all groups, viral levels in the blood peaked 12 days after treatment began. In the two monkeys treated earliest, this peaked at 71,000 copies of SIV RNA per millilitre of blood. Six weeks later, all detectable signs of the virus had disappeared.

Narrow window

In the pair of monkeys treated just three days later, viral levels peaked at 1.8 million copies of RNA per millilitre. This time it took three times as long, 18 weeks, to drive the virus down to undetectable levels.

In the remaining 18 monkeys not treated until three months after infection, viral levels peaked at 14 million copies of RNA per millilitre. But this time, even after 20 weeks of treatment, it proved impossible to eradicate all traces of the virus.

Seventeen weeks after infection, the levels of virus lurking in bone marrow, lymph nodes and gut tissue were 10 times higher, on average, in the monkeys treated at 10 rather than 7 days, even though the pairs were treated only three days apart.

These locations are important because this is where HIV is thought to establish long-lived reservoirs of dormant – non-replicating – virus. Since antiretroviral therapy works by disrupting viral replication, it has no effect on these reservoirs. This means the virus can re-emerge and re-establish infection if treatment is discontinued. This is probably the reason the virusbounced back in two men – the "Boston patients" – who initially appeared to have been purged of HIV following bone marrow transplants. The virus returned after the two had stopped drug treatment for 12 and 32 weeks respectively.

.Other AIDS researchers focusing on the quest for an outright cure are impressed by the work. "Okoye's study tells us that there's a very small window following infection in which early treatment can dramatically reduce the size of the reservoir," says Sharon Lewin of Monash University in Melbourne, Australia.