Researchers announced last week that the Mississippi baby who was once thought to be cured of HIV now has a detectable viral load and has been placed back on antiretroviral therapy (ART).
The case drew national media attention last March when doctors announced that the child, who was born HIV-positive and given high doses of ART immediately after birth, had been off of her medication for five months and that the virus was not detectable in her body. Her doctors believed they had successfully eradicated HIV in the young girl and announced their treatment plan as a possible treatment for other babies born with the virus.
Though the child remained off of medication and free of the virus for another year, it is now clear that she was not in fact cured.
Though standard practice would have been to prevent transmission of the virus to the baby by giving her mother drug therapy during pregnancy, her mother had not received such treatment. Upon learning this, the baby’s physicians decided to start the infant on a combination of three anti-retroviral drugs within 30 hours of her birth. The baby remained on this triple therapy for about 18 months and then disappeared from the system when her mother stopped coming to the clinic. When the baby returned at age 23 months, she had no detectable virus in her blood stream despite having been off of the medication for five months. Since that time, the girl, who is now two months shy of her fourth birthday and has been off ART for 27 months, has been monitored closely. She had been virus-free until last week, when routine testing found that her viral load had spiked and that her levels of CD4+ T cells had dropped.
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At the time of the announcement last spring, there was a lot of excitement around the child being “cured,” though some experts were skeptical. First, some questioned whether the infant had ever been HIV-positive or if the initial blood tests were just showing a virus that had spillover from her mother’s blood. Her doctors rejected that possibility and said that special tests done days after her birth showed that she had replicating virus in her bloodstream. The tests could not be replicated, however, because her doctors (who didn’t realize what would happen in this case) did not store the blood. Others also wondered how big a breakthrough this was given that mother-to-child transmission of HIV is preventable and this type of therapy would likely only work on infants.
Still, at the time her doctors were convinced this was a big breakthrough. They believed that by starting intensive drug therapies early, they were able to prevent the formation of so-called viral reservoirs—memory T-cells where HIV “takes up residence” and can hide for decades. Eradicating HIV from these memory T-cells has been the stumbling block to truly curing infected individuals. Based on the success in this case, the National Institutes of Health had planned to launch a global study to see if they could replicate the results by giving 54 HIV-positive infants standard antiretroviral drugs immediately after birth. Like the Mississippi baby, the children being studied would be kept on the drugs until the age of 2, at which time—if their viral loads were low enough—drug treatment would be stopped and they would be monitored closely to see if the virus returned. Given the news out of Mississippi this week, however, researchers may have to reexamine the planned study. Anthony Fauci, the director of the National Institute of Allergy and Infectious Disease, told Scientific American, “We are going to take a good hard look at the study and see if it needs any modifications.”
There have been other cases in which doctors announced they had eradicated HIV from an individual’s body, but HIV came back in all of those cases as well. The first was the case of Timothy Brown, an HIV-positive American man who was living in Germany when he needed a bone-marrow transplant to treat leukemia. The physician who was working on his case searched for a donor with a rare genetic mutation that is resistant to HIV. This mutation is present in about 1 percent of Caucasians, and the theory was that by replacing Brown’s own bone-marrow with cells that had this mutation, his body could fight the return of HIV. Brown’s transplant was in 2006, and as of 2010, when a peer-reviewed article about his case was published, he was considered virus-free without the help of medication. Since then, doctors have found some traces of HIV in his blood and tissues, but scientists disagree on what this means. It may be the result of a contamination in the testing process, he could have been reinfected, or it might mean that Brown was never actually “cured” of HIV. Interestingly, the HIV strains detected in his body were different than those he had in 2006. Again, scientists say this could be because Brown was reinfected or it could show that the virus “evolved and persist(ed) over the last 5 years.”
Two other men, known as the Boston patients, also received bone-marrow transplants for treatment of Hodgkin’s Lymphoma. Physicians monitored the men for several years and were intrigued when HIV remained undetectable in their bodies. As an experiment, the men agreed to stop taking their ART drugs so researchers could determine whether it was the drug treatment or the bone-marrow transplant that was keeping the virus in check. Last July, the researchers were excited to report that the men had been off their drugs for a period of time (for seven and 15 weeks, respectively), and HIV remained undetectable. Unfortunately, their excitement was short-lived. In August of that year, HIV became detectable in one of the men, who immediately went back on his medication. Researchers gave the other man the option of continuing to see if his HIV would return or going back on the medications. He opted to keep the experiment going, but by November HIV was detectable in his blood as well.
The doctors involved in the Boston case believe the results point to just how deep HIV reservoirs in the body are. Dr. Timothy Henrich told the Boston Globe last year that the latent cells throughout the body that carry the genetic code of HIV are more persistent than we realized. “[W]e need to look deeper, or we need to be looking in other tissues … the liver, gut, and brain,” he said. “These are all potential sources, but it’s very difficult to obtain tissue from these places so we don’t do that routinely.”
The doctors who’ve worked with the Mississippi baby are devastated by the latest test results. Dr. Hannah Gay, who treated the young patient, told Scientific American that it feels like a “punch in the gut.” However, Anthony Fauci of the National Institute of Allergy and Infectious Disease reminds us that these things take time. “We are still very much in the early discovery phase of trying to achieve a sustained virologic remission and perhaps even a cure,” he said.
In the meantime, the young girl in Mississippi has gone back on ART, her viral loads are back to undetectable levels, and her CD4+ T cells are down.