Sunday, March 3, 2013

A baby now free of HIV has doctors talking about 'cure'


Johns Hopkins Medicine
Dr. Deborah Persaud of the Johns Hopkins Children's Center. She helped discover the case of a toddler who is close to being "cured" of HIV.

A baby born infected with the AIDS virus who got immediate treatment now has no detectable virus in her blood – not quite a cure, but so close to one that it has doctors talking.

Her case, presented to a meeting of AIDS researchers that started Sunday, will prompt questions about how early babies should be treated – and further illustrates the possibility that immediate treatment with HIV drugs might stop infection in its tracks and could even have an impact on the AIDS pandemic.

“What we have identified is what we think is the first well-documented case of a functional cure in a neonatal child,” Dr. Deborah Persaud of the Johns Hopkins Children’s Center, the virologist who led the study, told NBC News.
 
A functional cure, says Persaud, means the virus isn’t entirely gone, but it’s not doing any damage, either. Doctors think it was because they began therapy for the baby within 48 hours of being infected, she said.
 
The child, who lives in rural Mississippi, is now 2 1/2 and healthy. She was, like so many, born to a mother who didn’t know until right before she gave birth that she had the human immunodeficiency virus (HIV) that causes AIDS. Mom and baby both got a standard dose of HIV drugs right away – something that has been shown to prevent what’s known as mother-to-child transmission of the virus in newborns.

The baby was a little premature and so stayed in the hospital. Within 30 hours of birth she was re-tested and had clear evidence of HIV infection. Unusually, she then got a cocktail of three drugs at a dose normally reserved for more advanced cases.  It worked really well – pushing her virus down to what’s called undetectable levels. This is what doctors want with HIV, because if the virus can’t be found in the blood, then it can’t be spreading and damaging the immune system. HIV doesn’t kill directly – it kills patients by damaging their immune systems so bad they can’t fight off other infections.

The baby and her mom, who doctors aren't naming, got regular care and treatment by Dr. Hannah Gay at University of Mississippi Medical Center until she was 15 months old. Then, like so many children, she disappeared off the doctors’ radar screens. She came back briefly at 18 months but disappeared again but she missed at least eight months worth of drugs. When Gay caught up to her again, the baby was still well, despite having received no treatment. More remarkably, tests showed the virus had not come back.

“My first thought was, ‘oh my goodness. We have been treating an uninfected child,” Gay told NBC News. "But I checked the records which confirmed she was, in fact, infected.

Dr. Katherine Luzuriaga of the University of Massachusetts School of Medicine, who also worked on the study, piled on with a battery of tests. Even a sensitive test called PCR, which can help find tiny bits of genetic material from a virus, couldn’t detect any evidence of HIV. This went far beyond the usual definition of "undetectable" in treating the AIDS virus - there really was no evidence the virus was there.

“What we did then was to get a group of collaborating laboratories together to apply ultra-sensitive testing  and say ‘can we detect any evidence of virus’,” Luzuriaga says. They did eventually find pieces of genetic material from the virus.

But Persaud has been unable to find any evidence of virus that can invade cells or replicate. “So the baby has remained off treatment. We are just watching and we will follow the baby and do additional testing.”
 
It’s not a true cure – what doctors call a “sterilizing” cure. There is still virus in the toddler’s body. But it’s not is a form that seems to be doing any damage. It doesn’t seem to be able to spread from one cell to another and it doesn’t seem to be damaging the child’s immune system.
 
About 34 million people globally are infected with HIV, the virus that causes AIDS; 25 million have died from it. While there’s no vaccine, cocktails of powerful antiviral drugs called antiretroviral therapy (ART) can keep the virus suppressed and keep patients healthy. No matter how long patients take ART, however, they are never cured. The virus lurks in the body and comes back if the drugs are stopped. Scientists want to flush out these so-called reservoirs and find a way to kill the virus for good.

“This has major implications for how we begin to think about treating children,” Persaud says. “Perhaps we can spare them a lifetime of treatment.”

But she adds, it’s one case.  “We need to figure out if this can be reproduced or replicated in other infants.”

Babies born to HIV-positive women are different from other HIV patients. Doctors know the precise moment that they are infected and can treat them right away. But usually they treat them with low doses of drugs for about six weeks and then wait to see if infection has really developed before they treat them again. If done right, this treatment around birth can prevent 95 percent of infections.

Up to now, only one person has been documented with a cure – the so-called Berlin patient, Timothy Brown, who was treated for leukemia with a bone marrow transplant that happened to come from a donor with a genetic mutation that makes immune cells resist HIV infection. The transplant replaced his own infected cells with healthy, AIDS-resistant cells. He is remains free of the virus more than five years later.

Dr. Dan Kuritzkes of Brigham and Women's Hospital and Harvard Medical School is treating two HIV other patients who, like Brown, got bone marrow transplants for leukemia or lymphoma. His team wants to see if they, too, can be cured. “They are doing fine,” he says – but continue taking HIV drugs to be safe.
But a third patient he was treating suffered a relapse of lymphoma and died. “It sort of underscores what these patients have been through,” he said. No one thinks a bone marrow transplant represents a real-life treatment for anyone with HIV, because it’s so hard on the body.

Kuritzkes said AIDS experts have wondered whether very early treatment of newborns could be in fact treating their infection rather than preventing it.

“It’s exciting because there are undoubtedly other children in this situation,” he said. His team is taking part in several studies looking at whether it is possible to eradicate the reservoirs of virus in adults that should have results within a year.
 
There are also patients called “elite controllers” who seem to stay well and suppress the virus without the need for drugs.
 
Luzuriaga says this toddler is not an elite controller. “You can detect HIV DNA in their cells. And you can culture virus from them,” she said. “We just think that this baby has much tighter control, much tighter control. This baby hasn’t rebounded off therapy.”

“Our next step is to find out if this is a highly unusual response to very early antiretroviral therapy or something we can actually replicate in other high-risk newborns,” says Persaud.

It might be that quick treatment stopped the virus from hiding out in the baby’s body, and allowed the drugs to do their work and stop the spread of the virus.

Ami Schmitz contributed to this story.
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