News Sexual Health

HIV Returns in Two Men Thought ‘Cured’ by Bone Marrow Transplants

Martha Kempner

Researchers in Boston announced last week that HIV had once again been detected in two patients who had previously been thought to be rid of the virus. The results suggest that HIV reservoirs, latent cells that have the genetic code of the virus, are more persistent and deeper in the body that scientists had thought.

Researchers in Boston announced last week that HIV had once again been detected in two patients who had previously been thought to be rid of the virus. The two men underwent bone marrow transplants several years ago as a treatment for Hodgkin’s lymphoma, a cancer of the blood. After the transplants, HIV was undetectable in the men’s blood. Earlier this year, both men agreed to stop taking their HIV medication so scientists could determine whether the bone marrow transplant had rid their bodies of HIV or whether the medication was keeping the virus in check.

In July, the researchers presented their initial, hopeful results. One of the men had been off of medication for seven weeks and the other for 15 weeks, and neither had any traces of HIV in their blood. This research followed the 2010 report of the “Berlin patient,” now known as Timothy Ray Brown, who was given a bone marrow transplant from a donor with a rare genetic mutation that is thought to be resistant to HIV. Brown’s transplant was in 2006, and he was virus-free as of 2010 when researchers published a peer-reviewed paper on his treatment. There has been some doubt cast on his “cure” since then, however, because in follow-up testing there were “signals of the virus,” but researchers were not able to determine if it was a re-emergence of HIV, a reinfection with a new strain of HIV, or just contamination in the test.

Regardless of the new results on Brown, scientists did not see his course of treatment as one that could be readily repeated in many patients. For one thing, there are a limited number of donors with the genetic mutation that resists HIV; it is thought to occur in only one in 100 Caucasians. Also, Brown was given very powerful chemotherapy and radiation, which many patients would not be strong enough to survive, to prepare his body for the bone marrow transplant.

The approach taken in Boston was more promising because it required less chemo and radiation and could use more readily available donors. Still, bone marrow transplants are risky and are only thought appropriate for HIV patients who are suffering from cancer that is not responding to other treatments. Nonetheless, doctors hoped that using bone marrow transplants to rid these patients of HIV could teach them more about the virus and lead to a more generalizable cure.

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In August, just a month after the initial announcement of success, HIV was once again found in one of the men in Boston. He began taking HIV medication immediately. The second patient was given the option of restarting his medication at that time but opted to continue the study. In November, HIV was detectable in his body as well, and he also started taking medication again.

The researchers have not yet analyzed their data, but felt it was important to announce this setback because other studies were being designed around their initial success. Dr. Timothy Heinrich, the lead researcher on the study, told the Boston Globe, “We felt it would be scientifically unfair to not let people know how things are going, especially for potential patients.”

He went on to say that the new finding suggests HIV reservoirs, latent cells throughout the body that carry the genetic code of HIV, are more persistent than we realized. He told the Globe, “[W]e need to look deeper, or we need to be looking in other tissues … the liver, gut, and brain. These are all potential sources, but it’s very difficult to obtain tissue from these places so we don’t do that routinely.”

The new results were met with widespread disappointment among scientists, but Heinrich and his team remain optimistic and believe that even though this experimental treatment was not successful, they learned a lot about the virus that can inform future treatments. “We go back to the drawing board,” said Heinrich. “It’s exciting science, even if it’s not the outcome we would have liked.”

News Sexual Health

HIV Found in Baby Who Was Previously Thought ‘Cured’ of the Virus

Martha Kempner

Doctors were devastated to announce last week that their patient, an almost 4-year-old girl was once thought "cured" of HIV, was found to have detectable viral loads and lowered T-cell counts.

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.

Analysis Sexual Health

Should We Call it a ‘Cure’? The Mississippi Child Who’s No Longer HIV-Positive

Martha Kempner

Do we do more harm than good when we bandy about the word "cure" in a case like this?

One of the big stories of the week is about a two-year-old girl from Mississippi who has, according to researchers, gone from being HIV-positive to not HIV-positive. If this finding is confirmed by further analysis, this would be only the second time HIV has been eradicated from a person’s body.

There are some scientific questions about the details of this case and whether the success could be replicated on a large scale. But an equally important question, in my mind, is whether we do more harm than good when we bandy about the word “cure” in a case like this.

The first time HIV was apparently eradicated from a person’s body was in the case of Timothy Brown, an American living in Germany who received a bone-marrow transplant as a treatment for leukemia. The blood cancer expert 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 one percent of Caucasians. The mutation apparently prevented the return of infection after the bone marrow transplant. Though researchers in California have found trace amounts of HIV in his tissues, Brown and his doctors say he remains HIV-free and that “any remnants of the virus still in his body are dead and can’t replicate.”

In the more recent case, doctors began intensive drug therapy on an infant born to an HIV-positive mother within 30 hours of birth. The mother had received no prenatal care and therefore had not received the drug therapies she would have needed to prevent mother-to-child transmission of the virus. The baby’s physicians decided to start her immediately on a combination of three anti-retroviral drugs. The baby remained on this triple therapy for about 18 months and then disappeared from the system when her mother stopped going to the clinic. When the baby returned at the age of 23 months, she had no detectable virus in her blood stream, despite having been off of the medication for five months. 

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How Big a Breakthrough Is This?

There are a few questions remaining about this case. Some scientists have questioned whether the toddler really was HIV-positive as an infant or if, instead, “the positive tests simply registered small amounts of the virus that had spilled over from the mother’s bloodstream during delivery.” If that is the case, this would not be a cure, but a successful case of post-exposure prophylaxis—a great outcome for this child, but not a new development. Her doctors have rejected that possibility, saying that special tests done days after her birth show that she had replicating virus in her bloodstream. The tests cannot be repeated as confirmation, however, because her doctors, who didn’t realize what would happen in the case, did not store the blood.   

The doctors believe 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 curing most infected individuals; Brown’s is the only other known case in which this has occurred.

If the treatment used on the toddler can be replicated, it may only work on infants, as it seems that treatment needs to be started immediately after birth. Still, there may be some hope for adult patients. Steven Deeks, an AIDS researcher at the University of California explains that “[t]he treatment of the Mississippi girl appears to have threaded the needle between bloodstream infection and permanent seeding of the memory T cells. Achieving that in adults, most of whom acquire HIV through sexual contact without knowing it, is exceedingly difficult. But it may not be impossible.”

In many ways, science has already solved the issue of mother-to-child transmission of HIV. Women who are known to be HIV-positive during pregnancy are given drug therapies that reduce the chance of infection in the infant from 30 percent to one percent. Most HIV-positive pregnant women in the United States receive this therapy, and only about 200 HIV-positive babies are born each year in the country. This case was a bit of an outlier, because the infant’s mother did not receive any prenatal care. (See Jim Merrel’s recent Rewire article for more on that part of the story.)

Worldwide, the numbers are different: Only about 60 percent of pregnant women receive the drug therapies they need, and approximately 330,000 babies are born each year with HIV, 91 percent of them in sub-Saharan Africa. While the Mississippi case provides a testable hypothesis for treating HIV-positive infants, it’s unclear whether this treatment would make much of a difference on a global level. Luiz Loures, deputy director for science at the Joint United Nations Programme on HIV/AIDS (UNAIDS), explained that it wouldn’t be hard to design a clinical trial to test the treatment used in Mississippi, but that “implementing it on a large scale is another matter. That would require laboratory equipment that detects the virus, which is not available in many rural settings in the developing world.”

Is “Cure” the Right Word?

The first time I heard the word “cure” associated with an HIV-positive individual, the headlines were about Earvin “Magic” Johnson, the basketball star who revealed he had the virus in 1991. By coming forward with his diagnosis when he did, Johnson helped bring greater awareness to the fact that it is important for everyone to prevent transmission and get tested for HIV.

In 1997, media outlets started to report that Johnson had been “cured” of HIV. His doctors quickly clarified that though he had undetectable levels of the virus in his blood, the virus was still in his body. “[W]e must emphasize that ‘undetectable’ doesn’t equal ‘absent.’ It would be premature and incorrect to say Earvin is ‘virus-free,'” said two of Johnson’s doctors in a statement at the time. Despite this explanation, the idea that Magic Johnson was “cured” of HIV has persisted—some websites even sell “cures” that Magic supposedly used.

In reality, Johnson represented an early success with Highly Active Anti-Retroviral Therapy (HAART). These drug cocktails were a major breakthrough in treating HIV and often have allowed HIV-positive individuals to live long and healthy lives. With the introduction of these therapies, HIV became a manageable disease for many individuals, rather than the death sentence it had once been.

The flip-side of this progress, however, is that many people become lax about HIV prevention and testing. This is exactly what AIDS activists feared when news of Magic Johnson’s “cure” came out 16 years ago. Lee Klosinsky, who was the director of education at the AIDS Project of Los Angeles at the time, told the LA Times, “My concern is that people are going to think that … he’s cured, that there’s a cure for AIDS, therefore, I don’t have to worry about being infected.” 

Individuals working today in the fields of HIV treatment and prevention have similar fears about the recent HIV “cure” stories making headlines. Joan Garrity, an HIV educator and trainer, explained to Rewire that messaging can be tricky in these cases. “I do wish they would stop using the work ‘cure’ for these individual cases. They could certainly refer to them as encouraging news, boosts to research, promising developments,” she said. “For the long-term survivors, they have heard this tempting term used so many times that it is almost meaningless, or feels like a set-up for disappointment. For those newly diagnosed it is probably somewhat encouraging. For the population of people we are trying to reach with prevention messages, it’s just not helpful. ”

Garrity reached out to a group of colleagues and people living with the disease to see how they felt about the use of the word “cure.” (They all asked to remain anonymous.) “I am a more than 30-year survivor of HIV, and am so tired of hearing about HIV/AIDS ‘cures,'” one HIV-positive individual said. “There is nothing so disheartening as to have your hope built up and then shot down. I prefer to think of these as potential advances in HIV treatment …. It also seems that people would be less likely to fund HIV-prevention programs if they thought there was a cure.”

Another person disagreed: “I have no problem with the use of the word ‘cure,’ if it can be proven. I pray that one day there will be a cure for all persons living with HIV/AIDS as well as all other ‘incurable’ diseases. So I am hopeful, and it is encouraging news.”

Still, there was agreement among many individuals she heard from that this could make prevention messaging harder. As Garrity pointed out, “Ever since the development of effective treatment to slow the progression of HIV, there’s been a struggle between how to convey the message that this is something to seriously avoid, and still give the newly infected the hope they need and even promises of the likelihood of a long lifespan.”

A colleague of Garrity’s put it this way: “I think it further lulls people into a sense of ‘by the time I would get sick they’ll have figured this out,’ and makes them less inclined to make protective sacrifices in the short run.”

Julie Davids, director of the HIV Prevention Justice Alliance, remembers being curious about the impact on prevention messages when Brown’s story became public a few years ago, but in retrospect feels that the attention it drew to HIV was a good thing. “It gave us an opportunity to talk about HIV and AIDS again and to remind people that it was still a big issue,” Davids told Rewire. She is not as worried this time. “If people come away thinking there’s a way for infants not to get HIV from their mothers, that’s okay, because it’s true,” she said. “I doubt this story will make any pregnant women decide to forgo prenatal care in favor of treating the baby this way. We can use it as an opportunity to remind people that mother-to-infant transmission is preventable.” 

In the end, stories like this are an opportunity. For scientists, they are an opportunity to learn more about how this very complicated virus works, how to treat it, and ultimately how to find a real cure that works for everyone. They are also an opportunity for advocates and educators to remind the public that HIV remains a real concern; progress is being made, and there is hope, but in the meantime prevention, testing, and treatment remain vital. Ultimately, maybe all news really is good news when battling public complacency around the HIV epidemic. Still, the word “cure” should not be thrown around too lightly or too often.

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