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In Medical First, a Baby With H.I.V. Is Called Cured
By ANDREW POLLACK and DONALD G. McNEIL Jr.
Published: March 3, 2013 28 Comments

Doctors announced on Sunday that a baby had been cured of an H.I.V. infection for the first time, a startling development that could change how infected newborns are treated and sharply reduce the number of children living with the virus that causes AIDS.
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Times Topic: AIDS / H.I.V.
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The baby, born in rural Mississippi, was treated aggressively with antiretroviral drugs starting around 30 hours after birth, something that is not usually done. If further study shows this works in other babies, it will almost certainly change the way newborns of infected mothers are treated all over the world. The United Nations estimates that 330,000 babies were newly infected in 2011, the most recent year for which there is data, and that more than 3 million children globally are living with H.I.V.

If the report is confirmed, the child born in Mississippi would be only the second well-documented case of a cure in the world, giving a boost to research aimed at a cure, something that only a few years ago was thought to be virtually impossible.

The first person cured was Timothy Brown, known as the “Berlin patient,’’ a middle-aged man with leukemia who received a bone-marrow transplant from a donor genetically resistant to H.I.V. infection.

“For pediatrics, this is our Timothy Brown,’’ said Dr. Deborah Persaud, associate professor at the Johns Hopkins Children’s Center and lead author of the report on the baby. “It’s proof of principle that we can cure H.I.V. infection if we can replicate this case.’’

Dr. Persaud and other researchers spoke in advance of a presentation of the findings on Monday at the Conference on Retroviruses and Opportunistic Infections in Atlanta.

Some outside experts, who have not yet heard all the details, said they needed convincing that the baby had truly been infected. If not, this would be a case of prevention, something already done for babies born to infected mothers.

“The one uncertainty is really definitive evidence that the child was indeed infected,” said Dr. Daniel R. Kuritzkes, chief of infectious diseases at Brigham and Women’s Hospital.

Dr. Persaud and some other outside scientists said they were certain the baby – whose name and gender were not disclosed – had been infected. There were five positive tests in the baby’s first month of life – four for viral RNA and one for DNA. And once the treatment started, the virus levels in the baby’s blood declined in the pattern characteristic of infected patients.

Dr. Persaud said there was also little doubt that the child experienced what she called a “functional cure.” Now 2½ , the child has been off drugs for a year with no sign of functioning virus.

The mother arrived at a rural hospital in the fall of 2010 already in labor and gave birth prematurely. She had not seen a doctor during the pregnancy and did not know she had H.I.V. When a test showed the mother might be infected, the hospital transferred the baby to the University of Mississippi Medical Center, where it arrived at about 30 hours old.

Dr. Hannah B. Gay, an associate professor of pediatrics, ordered two blood draws an hour apart to test for the presence of H.I.V. RNA and DNA.

The tests found a level of virus at about 20,000 copies per milliliter, fairly low for a baby. But since tests so early in life were positive, it suggests the infection occurred in the womb rather than during delivery, Dr. Gay said.

Typically a newborn with an infected mother would be given one or two drugs as a prophylactic measure. But Dr. Gay said that based on her own experience, she almost immediately used a three-drug regimen aimed at treatment, not prophylaxis, not even waiting for the test results confirming infection.

Virus levels rapidly declined with treatment and were undetectable by the time the baby was a month old. That remained the case until the baby was 18 months old, after which the mother stopped coming to the hospital.

When the mother and child returned five months later, Dr. Gay expected to see high viral loads in the baby. But the tests were negative.

Suspecting a laboratory error, she ordered more tests. “To my greater surprise, all of these came back negative,” Dr. Gay said.

Dr. Gay contacted Dr. Katherine Luzuriaga, an immunologist at the University of Massachusetts, who was working with Dr. Persaud and others on a project to document possible pediatric cures. The researchers, sponsored by amfAR, the Foundation for AIDS Research, put the baby through a battery of sophisticated tests. They found tiny amounts of some viral genetic material but no virus able to replicate, even lying dormant in so-called reservoirs in the body.

There have been scattered cases reported in the past, including one in The New England Journal of Medicine in 1995, of babies clearing the virus, even without treatment.

Those reports were greeted skeptically, particularly since testing methods were not very sophisticated back then. But those reports and this new one could suggest there is something different about babies’ immune systems, said Dr. Joseph McCune of the University of California, San Francisco.

One hypothesis is that the drugs killed off the virus before it could establish a hidden reservoir in the baby. One reason people cannot be cured now is that the virus hides in a dormant state, out of reach of existing drugs. When drug therapy is stopped, the virus can emerge from hiding.

“That goes along with the concept that, if you treat before the virus has had an opportunity to establish a large reservoir and before it can destroy the immune system, there’s a chance you can withdraw therapy and have no virus,’’ said Dr. Anthony S. Fauci, the director of the National Institute for Allergy and Infectious Diseases. Adults, however, typically do not know they are infected right as it happens, he said.

Dr. Steven Deeks, professor of medicine at the University of California, San Francisco, said if the reservoir never established itself, then he would not call it a true cure, though this was somewhat a matter of semantics. “Was there enough time for a latent reservoir, the true barrier to cure, to establish itself?’’ he said.

Still, he and others said, the results could lead to a new protocol for quickly testing and treating infants.

In the United States, transmission from mother to child is rare – several experts said there are only about 200 cases a year or even fewer, because infected mothers are generally treated during their pregnancies.

If the mother has been treated during pregnancy, babies are typically given six weeks of prophylactic treatment with one drug, AZT, while being tested for infection. In cases like the Mississippi one, where the mother was not treated during pregnancy, standards have been changing, but typically two drugs are used.

But women in many developing countries are less likely to be treated during pregnancy. And in South Africa and other African countries that lack sophisticated testing, babies born to infected mothers are often not tested until after six weeks, said Dr. Yvonne Bryson, chief of global pediatric infectious disease at the University of California, Los Angeles.

Dr. Bryson, who was not involved in the Mississippi work, said she was certain the baby had been infected and called the finding “one of the most exciting things I’ve heard in a long time.’’

Studies are being planned to see if early testing and aggressive treatment can work for other babies. While the bone marrow transplant that cured Timothy Brown is an arduous and life-threatening procedure, the Mississippi treatment is not and could become a new standard of care.

While it might be difficult for some poorer countries to implement, treating for only a year or two would be cost effective, “sparing the kid a lifetime of antiretroviral therapy,’’ said Rowena Johnston, director of research at amfAR.