Researchers say a newborn baby born with HIV has been functionally cured of the disease. Could it lead to a cure for HIV?
At the annual Conference on Retroviruses and Opportunistic Infections in Atlanta, scientists led by Dr. Deborah Persaud of Johns Hopkins University said that they had essentially cured a Mississippi baby of the HIV infection transmitted from its mother. The case is apparently the first in which a newborn was cured of the disease; only one other patient, Timothy Brown, known as the Berlin patient, is also believed to be cured. Brown was able to rid himself of the virus with a transplant of bone-marrow cells containing stem cells from a donor who had immune components able to thwart HIV. Brown received the transplant in 2006 and no longer needs to take anti-HIV drugs.
The baby’s mother was diagnosed with HIV when she arrived in the hospital to give birth; she had not received prenatal care, which includes therapies that can reduce transmission of HIV from mother to child by close to 100% if used properly. Doctors typically give infected mothers anti-HIV drugs several weeks or months before they give birth, as well as during labor, and continue the medications for the baby’s first six weeks. Even initiating the drugs during labor can significantly lower the risk of transmitting the virus; in the U.S., only about 25% of babies born to HIV positive mothers who don’t receive any treatment are infected with the virus, and that drops to a few percent with such interventions.
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If their mothers are HIV positive, newborns are generally given two antiretroviral drugs, or ARVs, on a just-in-case basis; at 6 weeks old, they are tested for the virus, and if they are positive, then their drug regimen is bumped up to a more aggressive therapy involving three anti-HIV drugs. If the babies are negative, they stop taking the medications.
In the Mississippi baby’s case, since the mother had not received any prenatal HIV care, her physician, Dr. Hannah Gay, decided to skip the six-week period on preventive drugs and jump directly to the more aggressive three-drug regimen within 30 hours of birth in order to give the baby the best chance of fighting off the virus. That idea of hitting the virus hard with drug treatments soon after infection to knock it out has been gaining ground in the HIV community in recent years, as studies show adults who have recently been exposed are able to lower their risk of infection if they begin anti-HIV therapy as soon as possible; more exciting results suggest that the medications can even prevent infection among healthy, uninfected individuals as well, if taken before high-risk activities such as unprotected sex.
After Gay began administering treatment, levels of the virus in the baby’s blood began to drop; they became undetectable about a month later. The baby continued to take a potent cocktail of drugs for about 18 months, after which the doctors lost contact with the infant’s family and later learned that the baby had stopped treatment. When the family returned for a checkup 10 months later, Gay and her team could not find signs of HIV in the toddler’s blood. Now 2 years and 6 months old, the child also showed no signs of antibodies to HIV, which suggests that the immune system is no longer seeing the virus and therefore does not need to generate defenses against HIV.
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“You always have to be careful when dealing with a single case,” says Dr. Anthony Fauci, director of the National Institutes of Health’s National Institute of Allergy and Infectious Diseases. “You really can’t make a broad extrapolation. But in my mind, this is an important conceptual advance.”
Fauci and other AIDS experts don’t anticipate that the results will lead to a change in the way that newborns, or pregnant women, are treated if they are infected. Existing therapies are already effective at lowering transmission of the virus from mothers to children, and the drugs used to battle HIV come with potentially toxic side effects. “If we are doing our job of identifying pregnant women who are HIV positive, treating them and managing their infant accordingly,” says Dr. Mark Kline, chairman of the Department of Pediatrics at Baylor College of Medicine and creator of the Baylor International Pediatric AIDS Initiative, “we should be preventing close to 100% of cases of pediatric HIV.”
But while effective, these methods aren’t foolproof, and the case raises intriguing questions about whether a cure for HIV is possible in babies who end up infected — and whether that possibility would make exposure to the powerful drugs worth the risk.
“If this is truly an effective way to actually cure a baby, then we what we want to throw into the risk-benefit ratio is the fact that if you cure a baby, you can stop therapy in that baby after a year or so, and you’ve saved that baby from 60 years of ARV therapy,” says Fauci.
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Confirming the result now becomes a priority for pediatric AIDS researchers, since there is still the possibility that the baby was on one of the rare but fortunate few who have a natural ability to keep HIV from establishing a foothold in the body. These elite controllers, or long-term nonprogressors, as they are known, harbor HIV in their blood, but are able to keep the levels of virus very low and suppress HIV’s activity enough to keep them free of any symptoms of infection. According to Johns Hopkins’ Persaud and her team, however, the toddler is not likely to be one of these, since the child does not show any signs of active HIV activity. Elite controllers often have enough virus in their system that it can be extracted from their blood and cultivated in a lab; while the child’s blood did show fragments of HIV genetic material, none of these elements could seed new viral growth on a lab dish. “Elite controllers have certain combinations of characteristics that we don’t see in this child,” says Rowena Johnston, vice president and director of research for amfAR, which provided grants to Persaud for some of her HIV work. “They have certain types of immune responses that are absent in this child, so this kid seems distinct from elite controllers and long-term nonprogressors.”
Further work will need to confirm whether that’s indeed the case, but in the meantime, Fauci says the finding should generate more research into how the newborn immune system, which is still immature and developing, interacts with HIV. “We don’t know a lot about the relationship between the virus and the immature immune system of a baby,” he says. “But it’s a really important question.” Those insights could lead to a better understanding of how even adult responses to HIV could be manipulated to better fight off infection and potentially keep HIV from progressing into advanced AIDS. “Once we have any new insights about the virus and immune system, it helps everything,” he says.
In addition, the case study also introduces the idea that curing HIV may not necessarily come in the form of a one-size-fits-all therapy. For newborns, it could involve hitting the virus hard with powerful anti-HIV drugs immediately after birth; for other groups, it may mean some other type of treatment. “Different populations are infected by different routes and different mechanisms, so how we cure infections may be achieved through different mechanisms,” says Johnston. “That’s a fascinating possibility that not a lot of people have thought about before.”