Doctors Pinpoint Why Child Who Appeared Free of HIV Suffered Relapse
HIV hid deep inside a young Mississippi girl born with the virus who suffered a disappointing relapse last July, after more than two years in which she appeared to have been cured by early, aggressive drug treatment, her doctors report.
They now know that the girl’s HIV was dormant all that time — not simply percolating undetected — because tests have shown that her recurring virus was an exact match to her mother’s HIV, said the girl’s pediatrician, Dr. Hannah Gay, of the University of Mississippi Medical Center, in Jackson.
“It appears that the virus had been dormant all of those many months and years, because there’s no evidence of diversity that would have been detected if low-level viral activity had been going on,” she explained.
Despite the setback, Gay and her colleagues believe that all babies born with HIV should receive the same rapid medical response as the Mississippi girl did, according to a letter they wrote in the Feb. 19 issue of the New England Journal of Medicine.
The girl, now nearly 5 years old, remained apparently virus-free for roughly two years after starting on a combination of three antiretroviral drugs within 30 hours of her birth.
Her remission continued even though she stopped taking HIV medications when she was 18 months old. Doctors had hoped her remission would open the door to a functional cure for all children born with the virus.
“Even though she did rebound, she had at least 27 months off of therapy,” Gay said. “That was 27 months of development without the ill effects of the virus and the ill effects of the medicines. This child benefited from a long remission.”
However, doctors should not assume that a child is HIV-free because they cannot detect any virus in their blood, Gay stressed.
In fact, it would be best if talk of a “functional cure” for HIV is dropped, Gay said.
“As we’ve studied this case and tried to describe her, we’ve developed a vocabulary of ‘remission’ rather than ‘functional cure,'” Gay said. “We think probably ‘remission and rebound’ or ‘remission and relapse’ are better and more communicative than ‘functional cure.'”
The girl’s relapse has reminded doctors that HIV is a sneaky virus that can hide deep in a person’s immune system.
The virus infects the “memory cells” of the immune system — cells that lie dormant deep within the system and retain the knowledge of how to respond to different types of infection. These cells wait in reserve, ready to be called upon to fight off a future illness.
HIV somehow found a way to quickly gain a foothold in the Mississippi girl’s immune system, despite the rapid and aggressive response to her condition. Because these cells are dormant, drug treatments that rid the bloodstream of HIV are not able to get inside them and kill off the virus hiding within.
“Somewhere inside the body of this child, there was at least one cell that had an intact infectious virus inside it,” said Rowena Johnston, vice president and director of research for amfAR, The Foundation for AIDS Research. “That cell or group of cells sat quietly and did nothing for two years, and then one day for some reason we don’t understand, it switched on and began replicating.”
Since the virus can hide so well, children born with HIV need to keep taking antiretroviral medication even if they appear virus-free, said Dr. Katherine Luzuriaga, a professor of molecular medicine and pediatrics at the University of Massachusetts Medical School in Worcester and lead author of the NEJM letter.
“What this and other cases tell us is our current efforts are not enough to prevent the formation of that reservoir of HIV in the body, or drop it low enough that patients can remain off antiretrovirals indefinitely,” Luzuriaga said.
Clinical trials are now underway that will further test this method of early, aggressive treatment for babies born with HIV, Luzuriaga and Johnston said.
Researchers hope that early treatment can prevent the development of a large HIV reservoir in these children, Gay said.
“If we can keep the reservoir very low, then as other interventions are developed, those kids are going to be the ones standing at the front of the line for a cure when that comes along,” she said.
This case also has shown researchers that they need better tests to detect HIV in the human body, Gay said.
“Our most sensitive measurements of the viral reservoir are not quite sensitive enough,” she said. “I think we suspected that already.”
Doctors normally put HIV-positive mothers on two antiretroviral medications prior to birth as a way of preventing transmission of the virus to their unborn children. After delivery, doctors test the newborns for HIV and continue treatment if the virus appears.
But in this girl’s case, no one knew the mother was HIV-positive before delivery. This prompted Gay to put the newborn on antiretroviral treatment immediately.
Tests showed progressively diminishing HIV levels in the infant’s blood, until it reached undetectable levels 29 days after birth. The child remained on antiretrovirals until 18 months of age, at which point doctors said they lost track of her and she stopped treatment.
Doctors next saw her about 10 months after her treatment ceased. The child underwent repeated standard HIV tests, which detected no virus in her blood.
This article appeared in US News & World Report written by Dennis Thompson on February 18, 2015. The original article can be found here.
Evidence of H.I.V. Found in a Child “Mississippi Baby” to Be Cured
A child in Mississippi who was thought to have been cured of H.I.V. with aggressive drug treatment immediately after birth is now 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 “Mississippi Baby” 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 H.I.V. in 2012, the last year for which figures were available; 260,000 were infants infected at birth or immediately afterward.
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 “Mississippi Baby” on large doses of antiretroviral drugs, said it was “like a punch in the gut.”
With hopes raised by the “Mississippi Baby” 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 H.I.V. 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 the director of the National Institute of Allergy and Infectious Diseases.
When 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 H.I.V. That was an adult, Timothy Ray 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 H.I.V. uses to enter the cell.
Dr. Anthony S. Fauci, the National Institute of Allergy and Infectious Diseases director, discussed the case of a child who was thought to have been cured of H.I.V. but is showing signs of infection.
Then last March, a second baby, born in Long Beach, Calif., 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 “Mississippi Baby” 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 baby 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 H.I.V. infection if we can replicate this case.”
On Thursday, Dr. Persaud said the fact that the child “Mississippi Baby” 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.
Dr. 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,” Dr. Fauci said. “That is an unequivocal relapse.”
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 H.I.V. 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.
This article appeared in the New York Times, written by Donald G. McNeil, Jr., published on July 11, 2014. It can be found here.