Virus has returned in a child in Mississippi thought to have been cured of an HIV infection, dashing hopes that scientists had found a strategy that would have widespread impact. After the girl went 27 months with no detectable virus in her blood, the sobering news “felt very much like a punch to the gut,” said her pediatrician, Hannah Gay of the University of Mississippi Medical Center in Jackson, who spoke at a media teleconference today.
The “Mississippi baby” received international attention in March 2013 when Gay and her collaborators first reported the case. The baby was believed to be just the second person who had a documented HIV infection that appeared to have been cleared. The girl, now 46 months old, received unusually aggressive treatment with a cocktail of antiretroviral drugs 30 hours after birth to an HIV-infected mother. Typically, doctors give HIV-exposed neonates a single antiretroviral until they confirm the virus was transmitted, which take several weeks. Her mother stopped her daughter’s treatment at 18 months, which almost invariably leads to rapid return of the virus.
As Gay and colleagues described in a detailed report that appeared in the 7 November 2013 issue of The New England Journal of Medicine (NEJM), ultrasensitive tests of the child’s blood done through 30 months of age found traces of HIV nucleic acid but no virus that could copy itself. The researchers suggested that the early aggressive treatment may have limited the size of the HIV “reservoir”—the stubborn pool that remains in people who have undetectable levels of virus—or somehow left only crippled remnants of it that could not replicate.
So much excitement built around this idea that the U.S. National Institute of Allergy and Infectious Diseases (NIAID) announced plans in March to conduct a clinical trial in other newborns. Now, “we’re going to take a good hard look at the study and see if it needs any modification,” said NIAID’s director, Anthony Fauci, who spoke today with Gay and others at the teleconference. “We have a situation that’s obviously disappointing, but nonetheless there certainly are many confounding issues that arise and that will trigger intense discussion and further study, particularly with regard to the persistence of a reservoir in the absence of our ability to detect it. What has happened with this case is really quite important.”
Steven Deeks, who conducts HIV cure research at the University of California, San Francisco, was surprised by the finding. “This virus is trickier than we thought,” Deeks said. “It drives home that we need even more supersensitive assays to detect a very little bit of virus. Or we’re going to have monitor these ‘clinically cured’ people for years.”
Gay discovered that the virus had returned when the child came in for a routine checkup last week, which she does every 6 to 8 weeks. Two separate blood tests showed more than 10,000 copies of HIV per milliliter of her blood. The child last tested negative on ultrasensitive assays in April; another blood draw from June is being analyzed now. She began treatment immediately last week, and Gay says her patient is doing fine.
In clinical studies of adults whose blood similarly tests negative for HIV, researchers often analyze more remote sites that can harbor reservoirs of virus, such as the lymph nodes, spinal fluid, or the gut. These tests typically are done before and after people decide to stop treatment. In the Mississippi case, the mother independently decided to stop treatment, so such before-and-after analyses were not warranted. “Obviously, this case highlights the need for that,” said Deborah Persaud, a pediatrician at the Johns Hopkins Children’s Center in Baltimore, Maryland, who headed the blood analyses and was lead author of the NEJM paper. “Further studies in the Mississippi child on antiretroviral treatment will help inform our [clinical trials] going forward.”