The newborn did test positive for viral DNA and RNA at two days old. She also tested positive at days seven, 12 and 20, but the viral load dropped off, indicating the drug cocktail was working as expected. The baby was given liquid ART every day: a combination of zidovudine, lamivudine and co-formulated lopinavir–ritonavir. At 29-days old, the child’s HIV RNA levels had fallen so low that they were undetectable in clinical tests. After 18 months, in January 2012, the mother stopped visiting to the clinic for unreported reasons. When the physicians tracked her and the baby down in autumn 2012 they found the viral RNA was still undetectable despite months off the anti-HIV medications. Only ultrasensitive tests revealed extremely low levels of the virus. They reported the case at the Conference on Retroviruses and Opportunistic Infections in Atlanta on March 3.
The case report’s lead-investigator Deborah Persaud, a virologist at Johns Hopkins University, also presented the results of a small study of teens infected with HIV at birth. Five of the teenagers received anti-HIV drugs at two months of age and carried lower viral DNA levels than four teens that had received the drugs later in childhood.
“Taken together, the findings of our two studies show that very early ART in infants prevents the development of long-term viral reservoirs, and in doing so may put newborns on a path to long-term remission and on the road to a functional cure,” Persaud said in a prepared statement.
The case is an important proof of concept, says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, who was not involved in the case. The DNA and RNA tests demonstrated that the baby had the virus for at least 10 or 12 days, indicating a probable, if early, infection. “The caveat is that this is still a single case,” he adds. “This is not something that is immediately generalizable, but it does tell you that under some circumstances there is a chance to cure.”
“It is a very interesting case report,” Mofenson says, who was also not involved in the Mississippi case. “It has some unusual aspects to it.” She first learned about the situation last year at a think tank for researchers. The mother presented with extremely low viral loads, which is unusual for an infected adult not taking anti-HIV drugs. The child’s first HIV tests also showed very low levels. These facts indicate that there is something unusual about the virus or the host, Mofenson says.
The new case may be a cure for just one child. Or it could be an anomaly—perhaps the child was never infected or is not actually cured, says Joseph M. McCune, a professor of experimental medicine at the University of California, San Francisco. He says he is most intrigued by the idea that the immaturity of a newborn’s immune system somehow enables it to cope better with the HIV infection. Previous research shows that the inflammatory response mounted by an immune system under threat can actually make the HIV virus grow more readily. An inflammatory response brings more immune cells to the site of injury or infection, increases cell division and boosts the production of molecules called cytokines. The HIV virus has evolved to take advantage of each of these processes—it spreads from cell to cell, so rapid division nearby helps HIV replicate quickly. Cytokines, which are small proteins that cells use to communicate, seem to be another cue the virus uses to know when to replicate, McCune says. But a newborn does not mount an inflammatory response as readily as an adult does. So the virus may take longer to fully infect a baby.