A child in Mississippi who was thought to have been cured of HIV with aggressive drug treatment immediately after birth is showing signs of infection with the virus, federal health officials announced Thursday - a serious setback to hopes for a cure for AIDS.
The report in March 2013 that the child had apparently been cured raised the possibility that aggressive early treatment might be able to reverse infections in newborns - and perhaps even in newly infected adults. About 2.3 million people around the world were newly infected with HIV in 2012, the last year for which figures were available; 260,000 were infants infected at birth or immediately afterward.
So Thursday’s announcement was especially deflating. During a telephone news conference held by the National Institutes of Health, Dr. Hannah B. Gay, the pediatrician at the University of Mississippi Medical Center in Jackson who first put the child on large doses of antiretroviral drugs, said it was “like a punch in the gut.”
With hopes raised by the Mississippi case, doctors had made plans for a worldwide clinical trial in which about 450 babies - chosen because their infected mothers had no testing or treatment before the births - would be put on the three-drug regimen called triple therapy.
If those who were infected with HIV showed no virus after 48 weeks of treatment, the plan was to stop their drugs and see if they had been cured before the virus had a chance to establish a reservoir of infected cells.
But not a single baby has yet been enrolled in the trial, and in light of the failure to cure the Mississippi baby, “We’ve got to go back and look at the trial’s design,” said Dr. Anthony S. Fauci, a leading AIDS expert who is director of the National Institute of Allergy and Infectious Diseases.
Asked how he felt about Thursday’s announcement, he said: “It’s obviously disappointing, but I was not surprised. I’ve been chasing these reservoirs for the last 25 years, and I know this virus has a really uncanny way of hiding itself.”
Before the Mississippi baby, only one other person had been considered cured of HIV. That was an adult, Timothy Brown, previously known as the anonymous “Berlin patient,” who had a transplant of blood stem cells to treat his leukemia after his bone marrow was wiped out with drugs and radiation. The new stem cells were from a matching donor who also had a relatively rare mutation that creates blood cells lacking the surface receptor that HIV uses to enter the cell.
Then last March, a second baby, born in Long Beach, California, appeared to have been cured after early and aggressive treatment. But doctors had been hesitant to declare that cure as definitively as they did in Mississippi case.
The mother in Mississippi had disappeared with her baby for several months after treatment began, and pediatricians assumed when they saw the baby again that it would be teeming with the virus. Instead, exhaustive tests found none in blood or tissue, and that remained true until several weeks ago when the virus was detected in the child’s blood during a routine office visit. By contrast, the California baby could not ethically be taken off antiretroviral drugs, which is the only sure test of whether the virus will rebound.
When the virus enters the body, it first invades the CD4 white blood cells and makes millions of copies of itself. It then starts entering lymph cells in the gut and elsewhere and uses its RNA core to make DNA mirror images of itself that then integrate themselves into the DNA of the cell, creating the reservoir.
After that, even if antiretroviral drugs suppress the ability of any free-floating RNA to copy itself, the DNA persists, waiting to act as a template for new RNA if the drugs are ever stopped.
The Mississippi case stirred worldwide excitement last year when it was described in The New England Journal of Medicine. Dr. Deborah Persaud, an associate professor at Johns Hopkins Children’s Center and the lead author of the report, said at the time that it was “proof of principle that we can cure HIV infection if we can replicate this case.”
On Thursday, Persaud said the fact that the child had remained virus-free for two years was “unprecedented.” Normally, the virus rebounds in a few weeks.
The child’s virus was identical to the mother’s, so there was no doubt that it was the virus passed at birth, not a later infection.
Fauci said the viral load was 16,000 copies of the virus per cubic millimeter of blood.
“You sometimes get a blip of 100 copies or 500 copies, but 16,000 is not a blip,” Fauci said. “That is an unequivocal relapse.”
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The child is now on triple therapy and is expected to stay that way, presumably for life unless a new route to a cure is found.
Last March, after the existence of the Long Beach baby was revealed, a leading AIDS researcher said there were anecdotal reports of five more such cases in Canada and three in South Africa.
It is very rare for children in wealthy countries to be born with HIV because most mothers are routinely tested in pregnancy and, if infected, put on triple therapy. Only in rare cases do mothers get no testing or prenatal care at all, and those are usually homeless and mentally ill women, as was the case in Long Beach.