A child born to an HIV-infected mother in Mississippi may be cured after a swiftly administered course of drugs. A number of factors make the child’s case unique, however, and clinicians caution that we have not discovered a general cure for HIV yet. Still, the medical first may hint at ways to fight the AIDS-causing virus.
An HIV cure has been elusive because the virus has ways of hiding within the body. It can secret itself into blood cells and other so-called reservoirs. Faced with powerful drugs that prevent viral replication, called antiretroviral therapy (ART), HIV levels in the blood drop down to nearly undetectable levels. Take the pressure off by halting treatment, however, and the virus comes roaring back.
Recent years have offered some hints about how to disable HIV’s assaults. A rare category of individuals, dubbed “elite controllers” can drop the drugs and still show no symptoms. Also, researchers are developing a treatment that will eliminate one of HIV’s entryways into immune cells through a gene-editing process. Yet, the best approach already available is to prevent infection, a daunting challenge despite decades of progress.
Preventing infection in the very young is a priority. Every day, approximately 1,000 babies are infected around the world with HIV during gestation, birth or breast-feeding, according to the United Nations Children’s Fund. Typically, newborns at risk of contracting HIV may receive one or two antiretroviral drugs prophylactically. If at six to eight weeks of age the baby tests positive for the viral antibodies, the physician will switch to the therapeutic cocktail and doses. The baby from Mississippi received a combination of the drugs zidovudine, lamivudine and nevirapine, just 30 hours after birth.
This aggressive treatment is not typical because antiretroviral drugs are toxic and infection is not always certain. The mother passes HIV antibodies on to her child during gestation. Only after six to eight weeks of life can clinicians tell whether the baby is actually infected with HIV and not simply carrying the mother’s antibodies. “These drugs are not like vitamins,” says Lynne Mofenson, chief of the Maternal and Pediatric Infectious Disease Branch at the National Institute of Child Health and Human Development. “You only use them when the child is at high risk.”
Current guidelines in the U.S. recommend that expectant mothers who are infected with HIV receive drugs during pregnancy. Then, babies should be delivered via cesarean section and be formula-fed. Those recommendations can minimize the risk of transmission to less than 1 percent Mofenson says. Accordingly, mother-to-child transmission of the virus is rare in developed nations but much more common where anti-HIV drugs are scarce. Currently, fewer than 200 children in the U.S. are born HIV-positive each year.
The mother in the new case did not receive any prenatal care or ART. She arrived at the clinic in labor and delivered her baby prematurely (at 35 weeks into her pregnancy). When a test came back showing she was HIV-positive, University of Mississippi Medical Center pediatric HIV specialist Hannah Gay determined that the risk to the child was great. Therefore she decided to treat, even though clinicians hadn’t confirmed that the baby was infected.
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.
The immune response of the fetus differs from that of the newborn as well because cells from the mother move across the placenta and enter the fetus. “The fetus doesn’t want to make an inflammatory response against mother,” McCune says. “So the fetus has developed an immune system that says ‘do not respond.’” That calming of the immune response may hold over to the first few days of the newborn’s life; the inflammatory response does not fully activate, robbing the new HIV infection of additional fuel. This delay, combined with a short course of aggressive treatment, may give the body enough of a head start to eradicate the virus on its own, he notes.
“It’s very exciting,” McCune says. “Many revolutions in medicine have occurred because of a single case.”
Mofenson cautions that the result from the Mississippi case does not mean that clinicians and pediatricians should change any of their practices yet. Even children or older patients with very low viral load levels should continue antiretroviral therapy. There are “multiple questions raised by this case that really need urgent and further research.” To that end, her institute has put out a call for research proposals. “Now people are aware of this and can bring other children to our attention,” she says. “Hopefully, within a year or two we will have better answers.”