London man seems to be free of HIV in second such case</s>An HIV-positive man in Britain has become the second-known adult worldwide to be cleared of the Aids virus after he received a bone marrow transplant from an HIV-resistant donor, his doctors said.

Highly sensitive tests show no trace of the man’s previous HIV infection almost three years after receiving bone-marrow stem cells from a donor with a rare genetic mutation that resists HIV infection – and more than 18 months after coming off antiretroviral drugs.

“There is no virus there that we can measure. We can’t detect anything,” said Prof Ravindra Gupta, an HIV biologist who co-led a team of doctors treating the man.

The case is a proof of the concept that scientists will one day be able to end Aids, the doctors said, but it does not mean a cure for HIV has been found.

Prof Gupta described his patient as “functionally cured” and “in remission”, but he cautioned: “It’s too early to say he’s cured.”

The man is being called “the London patient”, in part because his case is similar to the first known case of a functional cure of HIV - in an American man, Timothy Brown, who became known as the Berlin patient when he underwent similar treatment in Germany in 2007 which also cleared his HIV.

Mr Brown, who had been living in Berlin, has since moved to the United States and, according to HIV experts, is still HIV-free.

Some 37 million people worldwide are currently infected with HIV and the Aids pandemic has killed around 35 million people worldwide since it began in the 1980s.

Scientific research into the complex virus has in recent years led to the development of drug combinations that can keep it at bay in most patients.

Prof Gupta, now at Cambridge University, treated the London patient when he was working at University College London. The man had contracted HIV in 2003, the professor said, and in 2012 was also diagnosed with a type of blood cancer called Hodgkin’s Lymphoma.

In 2016, when he was very sick with cancer, doctors decided to seek a transplant match for him. “This was really his last chance of survival,” Prof Gupta told Reuters in an interview.

The donor - who was unrelated - had a genetic mutation known as ‘CCR5 delta 32’, which confers resistance to HIV.

The transplant went relatively smoothly, Prof Gupta said, but there were some side effects, including the patient suffering a period of “graft-versus-host” disease - a condition in which donor immune cells attack the recipient’s immune cells.

Most experts say it is inconceivable such treatments could be a way of curing all patients. The procedure is expensive, complex and risky. To do this in others, exact match donors would have to be found in the tiny proportion of people ? most of them of northern European descent ? who have the CCR5 mutation that makes them resistant to the virus.

Specialists said it is also not yet clear whether the CCR5 resistance is the only key - or whether the graft versus host disease may have been just as important. Both the Berlin and London patients had this complication, which may have played a role in the loss of HIV-infected cells, Prof Gupta said.

The London patient, whose case was set to be reported in the journal Nature and presented at a medical conference in Seattle on Tuesday, has asked his medical team not to reveal his name, age, nationality or other details. – Reuters</s>Image copyright Getty Images Image caption HIV was no longer detected in the patient's body after the transplant

A UK patient's HIV has become "undetectable" following a stem cell transplant - in only the second case of its kind, doctors report in Nature.

The London patient, who was being treated for cancer, has now been in remission from HIV for 18 months and is no longer taking HIV drugs.

The researchers say it is too early to say the patient is "cured" of HIV.

Experts say the approach is not practical for treating most people with HIV but may one day help find a cure.

The male London patient, who has not been named, was diagnosed with HIV in 2003 and advanced Hodgkin's lymphoma in 2012.

He had chemotherapy to treat the Hodgkin's cancer and, in addition, stem cells were implanted into the patient from a donor resistant to HIV, leading to both his cancer and HIV going into remission.

Researchers from University College London, Imperial College London, Cambridge and Oxford Universities were all involved in the case.

'Not an anomaly'

This is the second time a patient treated this way has ended up in remission from HIV.

Ten years ago, another patient in Berlin received a bone-marrow transplant from a donor with natural immunity to the virus.

Timothy Brown, said to be the first person to "beat" HIV/Aids, was given two transplants and total body irradiation (radiotherapy) for leukaemia - a much more aggressive treatment.

"By achieving remission in a second patient using a similar approach, we have shown that the Berlin patient was not an anomaly and that it really was the treatment approaches that eliminated HIV in these two people," said lead study author Prof Ravindra Gupta, from UCL.

Hope of a cure?

By BBC Online Health Editor, Michelle Roberts

Although the finding is exciting, it is not offering up a new treatment for the millions of people around the world living with HIV.

The aggressive therapy was primarily used to treat the patient's cancer, not his HIV.

Current HIV therapies are really effective, meaning people with the virus can live long and healthy lives.

But the reason this case is so significant is that it could help experts who are looking for new ways to tackle HIV and achieve a cure.

Understanding how the body can naturally resist the infection does offer up hope of this, even if it is still a long way off.

Prof Eduardo Olavarria, also involved in the research, from Imperial College London, said the success of stem cell transplantation offered hope that new strategies could be developed to tackle the virus.

But he added: "The treatment is not appropriate as a standard HIV treatment because of the toxicity of chemotherapy, which in this case was required to treat the lymphoma."

Image copyright Getty Images Image caption The patient was able to stop taking antiretroviral therapy drugs to control his HIV

How does it work?

CCR5 is the most commonly used receptor by HIV-1 - the virus strain of HIV that dominates around the world - to enter cells.

But a very small number of people who are resistant to HIV have two mutated copies of the CCR5 receptor.

This means the virus cannot penetrate cells in the body that it normally infects.

The London patient received stem cells from a donor with this specific genetic mutation, which made him resistant to HIV as well.

But a reservoir of cells carrying HIV can still remain in the body, in a resting state, for many years.

The UK researchers say it may be possible to use gene therapy to target the CCR5 receptor in people with HIV, now they know the Berlin patient's recovery was not a one-off.

Prof Graham Cooke, National Institute for Health Research research professor and reader in infectious diseases from Imperial College London, said the results were "encouraging".

"If we can understand better why the procedure works in some patients and not others, we will be closer to our ultimate goal of curing HIV.

"At the moment the procedure still carries too much risk to be used in patients who are otherwise well."

'Potentially significant'

Dr Andrew Freedman, reader in infectious diseases and honorary consultant physician at Cardiff University, said it was an "interesting and potentially significant report".

But he said much longer follow-up would be needed to ensure the virus did not re-emerge at a later stage.

"While this type of treatment is clearly not practical to treat the millions of people around the world living with HIV, reports such as these may help in the ultimate development of a cure for HIV."

In the meantime, he said the focus needed to be on diagnosing HIV promptly and starting patients on lifelong combination antiretroviral therapy (cART).

This can prevent the virus being transmitted to others and give people with HIV a near-normal life expectancy.</s>HIV (yellow) infecting a human immune cell (blue).Credit: NIH/SPL

A person with HIV seems to be free of the virus after receiving a stem-cell transplant that replaced their white blood cells with HIV-resistant versions. The patient is only the second person ever reported to have been cleared of the virus using this method. But researchers warn that it is too early to say that they have been cured.

The patient — whose identity hasn’t been disclosed — was able to stop taking antiretroviral drugs, with no sign of the virus returning 18 months later. The stem-cell technique was first used a decade ago for Timothy Ray Brown, known as the ‘Berlin patient’, who is still free of the virus.

How to beat HIV

So far, the latest patient to receive the treatment is showing a response similar to Brown’s, says Andrew Freedman, a clinical infectious-disease physician at Cardiff University in the UK who was not involved in the study. “There’s good reason to hope that it will have the same result,” he says.

Like Brown, the latest patient also had a form of blood cancer that wasn’t responding to chemotherapy. They required a bone-marrow transplant, in which their blood cells would be destroyed and replenished with stem cells transplanted from a healthy donor.

But rather than choosing just any suitable donor, the team — led by Ravindra Gupta, an infectious-disease physician at the University of Cambridge, UK — picked a donor who had two copies of a mutation in the CCR5 gene that gives people resistance to HIV infection. This gene codes for a receptor which sits on the surface of white blood cells involved in the body’s immune response. Normally, the HIV binds to these receptors and attacks the cells, but a deletion in the CCR5 gene stops the receptors from functioning properly. About 1% of people of European descent have two copies of this mutation and are resistant to HIV infection.

Gupta’s team describes the results in a paper due to be published in Nature on 5 March. The researchers report that the transplant successfully replaced the patient’s white blood cells with the HIV-resistant variant. Cells circulating in the patient’s blood stopped expressing the CCR5 receptor, and in the lab, the researchers were unable to re-infect these cells with the patient’s version of HIV.

The team found that the virus completely disappeared from the patient’s blood after the transplant. After 16 months, the patient stopped taking antiretroviral drugs, the standard treatment for HIV. In the latest follow-up, 18 months after stopping medication, there was still no sign of the virus.

Aggressive treatment

Gupta says that it’s not yet possible to say whether the patient has been cured. This can only be demonstrated if the patient’s blood remains HIV free for longer, he says.

But the study does suggest that Brown’s successful treatment ten years ago wasn’t just a one-off. Gupta says that the latest patient received a less aggressive treatment than Brown to prepare for the transplant. The new patient was given a regimen consisting of chemotherapy alongside a drug that targets cancerous cells, while Brown received radiotherapy across his entire body in addition to a chemotherapy drug.

This suggests that, to be successful, stem-cell transplants in HIV patients would not necessarily need to be accompanied by aggressive treatments that might have particularly severe side effects, says Gupta. “The radiation really does knock the bone marrow and make you very sick.”

Graham Cooke, a clinical researcher at Imperial College London, points out that this kind of treatment wouldn’t be suitable for most people with HIV — who don’t have cancer and so don’t need a bone-marrow transplant, which is a serious procedure that can sometimes have fatal complications. “If you’re well, the risk of having a bone-marrow transplant is far greater than the risk of staying on tablets every day,” he says. Most people with HIV respond well to daily antiretroviral treatment.

But Cooke adds that for those who need a transplant to treat leukaemia or other diseases, it seems reasonable to try and find a donor with the CCR5 mutation, which wouldn’t add any risk to the procedure.

Gero Hütter, who led Brown’s treatment and is now medical director of the stem-cell company Cellex in Dresden, Germany, agrees that this kind of treatment could only ever be used for a small group of patients. But he hopes that the paper will stimulate a renewed interest in gene therapies that target CCR5, which could be applied to a much broader group. “The real breakthrough, we are still waiting for,” he says.</s>A HIV positive man known as the London Patient has become the second known person to show long term remission from HIV.

A HIV positive man known as the London Patient has become the second known person to show long term remission from HIV.

A HIV positive man has become the second person to go into sustained remission from the virus and cleared of AIDS after receiving a bone-marrow transplant.

The case is the second ever observed of sustained HIV remission according to a UK study, although the authors say it's too early to confirm whether the patient is indeed "cured" of the virus which causes AIDS. The man, known as the "London Patient", has been in remission for 19 months.

Another patient, Timothy Brown, known as the "Berlin Man" was sent into remission 10 years ago by a similar treatment, but attempts to replicate the result have failed until now.

The London Patient received a transplant of stem cells from a donor who had the rare gene mutation CCR5. The mutation is related to HIV resistance.

The London Patient stopped taking antiretroviral drugs 19 months ago, with "no viral rebound", which Peter Doherty Institute for Infection and Immunity director Professor Sharon Lewin called "impressive."

"Coming 10 years after the successful report of the Berlin Patient, this new case confirms that bone marrow transplantation from a CCR5-negative donor can eliminate residual virus and stop any traces of virus from rebounding," Prof Lewin said.

Experts said the results were exciting, but remained conservative about current capabilities of widespread replication of the "cure" for the tens of millions of people affected by HIV worldwide.

'WE NEED TO BE CAUTIOUS'

"This is a very interesting and encouraging result; however we need to be cautious for a number of reasons," UNSW's Kirby Institute director Professor Anthony Kelleher said.

"Firstly, the bone marrow transplant in both HIV cure cases were primarily used to treat cancers of the blood and were modified to enable a HIV cure. So, the cost benefit of the prognosis following a bone-marrow transplant versus that on HIV antiretroviral therapy needs serious consideration.

"Secondly, naturally resistant and compatible bone marrow donors are rare because of the need for donor recipient matching. Further, this type of procedure is not widely available in many countries.

"Finally, there is significant morbidity and mortality associated with this type of transplantation, even when conducted in the best centres, and under the best circumstances.

"While there are important limitations to applying this study to a HIV cure globally, this second documented case does reinforce the message that HIV cures are possible.

"Common to both approaches is the presence of a modified gene in our immune system (CCR5) that is necessary for HIV infection.

"This tells us that the feasibility, and importantly, the availability of delivering this approach could possibly be achieved by the rapidly accelerating field of gene editing and related gene therapies.

"However, there are still significant hurdles in this field as well."

The CCR5 gene is also associated with controversial "gene editing" by Chinese scientist He Jiankui last year, that led to the birth of the world's first gene-edited twin babies.

In Australia, about 25,000 people were living with HIV.

Worldwide about 36.9 million people are HIV positive and living with AIDS.</s>Doctors in London say they have apparently eradicated HIV from a patient's body. It's only the second time this has been accomplished, despite many attempts over more than a decade.

While some commentators are calling this a "cure" for HIV, the scientists who performed the experiment say it's too soon to say that. Instead, they say the patient is in remission.

Both cases involved a risky procedure called a stem-cell transplant (otherwise known as a bone marrow transplant). The first recipient, Timothy Brown, gained fame as the so-called Berlin patient after transplants in 2007 and 2008 rid him of HIV. He remains free of HIV today.

That result raised hopes that HIV could be eradicated through a medical procedure and cure people of HIV infection. Yet Brown's case remained the lone success since then. Other attempts had failed.

Now, researchers at Imperial College London report in a paper being published Tuesday in Nature that they have apparently eliminated HIV in a second person.

That man had been diagnosed with HIV in 2003. Then, in 2012 the unidentified patient was diagnosed with a cancer, Hodgkin lymphoma. After standard treatments failed, they gave the patient a stem-cell transplant — essentially killing off his old immune system and giving him a new one.

The doctors selected a donor who had two copies of a particular mutation in the CCR5 gene that prevents HIV from infecting T-cells, a part of the immune system where the virus takes hold and does its damage. As a result, the man ended up with an immune system that was naturally resistant to HIV.

Sixteen months after the man's transplant, doctors found no sign of HIV in his body. They decided to stop treating him with antiviral drugs after he volunteered to stop taking them. It has now been more than 18 months and the infection hasn't reappeared, the scientists say.

Ravindra Gupta and his colleagues write, "it is premature to conclude that this patient has been cured," but they are hopeful that will prove to be the case.

"This is a highly significant study," Aine McKnight, a professor of viral pathology at Queen Mary University of London, said in a statement. "After a ten year gap it provides important confirmation that the 'Berlin patient' was not simply an anomaly."

But McKnight cautioned that this won't necessarily lead to a treatment for anyone with HIV. For one thing, the rare mutation in this case, a variant of a receptor called CCR5, only blocks one variety of HIV. A second, less common form of HIV could still cause infection despite a transplant like this.

This receptor was recently in the news after Chinese scientist He Jiankui claimed he had edited the genes of embryos to include a protective version of CCR5. This experiment raised an ethical furor.

AIDS researchers have known about this CCR5 mutation for years and have tried to think of ways to exploit it as a treatment for HIV.

"Although it is not a viable large-scale strategy for a cure, it does represent a critical moment in the search for an HIV cure," Anton Pozniak, president of the International AIDS Society, said in a statement. "These new findings reaffirm our belief that there exists a proof of concept that HIV is curable."

Stem-cell transplants are expensive and risky, because they involve wiping out a patient's immune system with powerful drugs or radiation and then reconstituting it.

The benefits of this treatment outweigh the risk for cancer patients, which is where it is most commonly used. But HIV drugs have become so effective that many people carrying this infection have a normal lifespan if they take these medications for a lifetime.

The scientists note in their study that the treatment for the second patient was less harsh than the one used for the Berlin patient, raising the possibility that they could develop a less risky procedure for stem-cell transplants for HIV-positive patients.

They say this procedure could be useful now for those rare people with HIV who have also been diagnosed with cancer and are in need of a stem-cell transplant to reconstitute their immune systems. Those patients could benefit if they can find a donor with the rare mutation in CCR5 that protects them from HIV reinfection.

You can contact NPR Science Correspondent Richard Harris at rharris@npr.org.</s>LONDON- An HIV-positive man in Britain has become the second known adult worldwide to be cleared of the AIDS virus after he received a bone marrow transplant from an HIV resistant donor, his doctors said.

Almost three years after receiving bone marrow stem cells from a donor with a rare genetic mutation that resists HIV infection — and more than 18 months after coming off antiretroviral drugs — highly sensitive tests still show no trace of the man's previous HIV infection.

"There is no virus there that we can measure. We can't detect anything," said Ravindra Gupta, a professor and HIV biologist who co-led a team of doctors treating the man.

The case is a proof of the concept that scientists will one day be able to end AIDS, the doctors said, but does not mean a cure for HIV has been found.

Gupta described his patient as "functionally cured" and "in remission", but cautioned: "It's too early to say he's cured."

The man is being called "the London patient", in part because his case is similar to the first known case of a functional cure of HIV - in an American man, Timothy Brown, who became known as the Berlin patient when he underwent similar treatment in Germany in 2007 which also cleared his HIV.

Brown, who had been living in Berlin, has since moved to the United States and, according to HIV experts, is still HIV-free.

Some 37 million people worldwide are currently infected with HIV and the AIDS pandemic has killed around 35 million people worldwide since it began in the 1980s. Scientific research into the complex virus has in recent years led to the development of drug combinations that can keep it at bay in most patients.

Gupta, now at Cambridge University, treated the London patient when he was working at University College London. The man had contracted HIV in 2003, Gupta said, and in 2012 was also diagnosed with a type of blood cancer called Hodgkin's Lymphoma.

In 2016, when he was very sick with cancer, doctors decided to seek a transplant match for him. "This was really his last chance of survival," Gupta told Reuters in an interview.

The donor — who was unrelated — had a genetic mutation known as 'CCR5 delta 32', which confers resistance to HIV.

The transplant went relatively smoothly, Gupta said, but there were some side effects, including the patient suffering a period of "graft-versus-host" disease - a condition in which donor immune cells attack the recipient's immune cells.

Most experts say it is inconceivable such treatments could be a way of curing all patients. The procedure is expensive, complex and risky. To do this in others, exact match donors would have to be found in the tiny proportion of people — most of them of northern European descent — who have the CCR5 mutation that makes them resistant to the virus.

Specialists said it is also not yet clear whether the CCR5 resistance is the only key — or whether the graft versus host disease may have been just as important. Both the Berlin and London patients had this complication, which may have played a role in the loss of HIV-infected cells, Gupta said.

While the London patient is in remission, Dr. Anthony Fauci told NBC News it is not a "scalable, feasible" way to treat HIV.

"This is something that was done under the very special circumstance of an individual who had Hodgkin’s disease and needed a bone marrow transplant for his underlying cancer-like disease," said Fauci. "The misperception that’s floating out there now is that bone marrow transplantation is now a cure for HIV infection and that is completely untrue."

In Fauci's view, the priority should be getting patients access to the "extremely efficacious medications that we have."

The treatment called pre-exposure prophylaxis, or PrEP, is more than 99 percent effective in preventing infection if patients take the medication every day.

"In the overwhelming majority of people, you could bring down the virus to below detectable levels that would save the life of the individual, as well as make it impossible for that person to spread the virus to someone else," Fauci said.

While the bone marrow transplant finding is very promising, Dr. Daniel R. Kuritzkes said it's not the kind of therapy that could be used on healthy patients with HIV.

“It’s highly unlikely that stem cell therapy will be the way to go,” said Dr. Daniel R. Kuritzkes, director of AIDS research at Brigham and Women's Hospital in Boston who has treated HIV patients in the U.S. with bone marrow transplants, told NBC News. “There are too many risks. There have been five or six others treated in a similar way who died either from their underlying cancer or from complications of the treatment."

Although the procedure is not a new concept, it does show researchers a way forward, said AIDS expert Jonathan Jacobs, founder of the Center for Special Studies at NewYork-Presbyterian/Weill Cornell Medical Center. “So there is promise here, but the practical reality is that this treatment can be fatal and it’s very expensive."

Gupta said his team plans to use the findings to explore potential new HIV treatment strategies. "We need to understand if we could knock out this (CCR5) receptor in people with HIV, which may be possible with gene therapy," he said.

The London patient, whose case was reported in the journal Nature and presented at a medical conference in Seattle Tuesday, has asked his medical team not to reveal his name, age, nationality or other details.</s>A man in London has become only the second person to achieve remission from HIV infection, researchers from the UK reported Tuesday. The therapy responsible has worked on only one other person who is considered to be “cured” of HIV: Timothy Ray Brown, who still does not show signs of the virus in his body after more than 10 years.

Here’s what to know about the landmark case.

How did it happen?

In a letter published in the journal , researchers led by Ravindra Gupta from the University of Cambridge London and Imperial College London and his colleagues say that they used a treatment similar to the one Brown received in 2007, but with a few changes meant to make the therapy easier and less intense for the patient. The London patient, who wishes to remain anonymous, was diagnosed with HIV in 2003 but did not begin anti-HIV drug therapy, which can keep the virus below detectable levels, until 2012. That year, he was also diagnosed with stage 4 Hodgkin’s lymphoma.

To treat his cancer, he received chemotherapy and a bone marrow transplant in 2016; the chemotherapy killed the malignant and healthy cells in his immune system and blood, while the transplant gave him a fresh start with bone marrow cells from a healthy donor, which seeded a new population of cancer-free immune and blood cells. Brown had received two similar transplants to treat his leukemia; his donors were intentionally chosen because they not only matched him, but they also harbored genetic mutations that made their cells nearly impervious to HIV infection. These mutations are in a gene called CCR5, which HIV normally recognizes in immune cells and uses like a key to enter and infect them. But with the mutated CCR5, Brown’s immune cells became molecular fortresses that HIV couldn’t penetrate — which meant the transplant essentially cured him of his infection.

For the London patient, Gupta and his team also found a donor who had these mutations in CCR5. The patient remained on anti-HIV drugs to prevent the virus from replicating for nearly 1.5 years after the transplant; because HIV tends to hide in cells in a dormant phase and reactivate years later, Gupta wanted to be sure that as much of the virus as possible was destroyed with the drugs. Then in 2017, Gupta took the London patient off of the anti-HIV drugs to see if the transplant had worked as it had in Brown’s case: to push the HIV into remission. Indeed, 16 months later, his virus remains at below detectable levels, and his immune cells all contain the HIV-fighting CCR5 mutation.

Does this mean HIV has been cured?

It’s a matter of semantics, says Dr. Steven Deeks, professor of medicine at the University of California, San Francisco and one of the doctors who treated Brown. “Is that a cure? I think so.” He says he believes that some HIV still remains in the London patient’s body, but that because his immune system is now impervious to the virus, the HIV is marooned — like a castaway on a remote island who cannot swim. HIV is at its most dangerous when it is actively replicating, furiously producing as many copies of itself as possible so it can penetrate immune cells and spread infection. That’s when it can also mutate to evade drugs. Because it’s a virus, it can’t replicate on its own, but instead needs to co-opt the machinery of another cell in order to reproduce, so it can only replicate when it infects other cells. But if HIV is surrounded by a sea of CCR5-mutated cells that it can’t exploit, it’s stymied.

“Personally I think there is probably some virus somewhere in the body, but it’s absolutely trapped,” says Deeks. “It may persist there for quite some time, but who cares? It can’t grow, it can’t replicate, it can’t spread — it can’t cause any problems.”

Still, HIV has proven before to be a wily shapeshifter, and except for Brown, people who previously went in remission for various reasons for a year or so have always seen their virus start to replicate again. Even a newborn girl in Mississippi, who was treated with anti-HIV drugs minutes after being born to an HIV-positive mother and remained in remission for about four years without medications, saw her HIV return and needed to go back on drug therapy.

Could the patient’s HIV come back?

Possibly. The London patient’s immune system is now designed to block HIV’s most common path into cells, using the CCR5 receptor. But the virus is clever and comes in another form that can use a different, side entrance into cells through another receptor called CXCR4. HIV can mutate from using CCR5 to relying on CXCR4, but in order to do that, it needs to be actively replicating. For now, experts believe that any remaining HIV in the London patient isn’t able to replicate at the pace it needs to change into a different form.

Yet there may be another reason to be cautious about the London patient’s potential remission. He waited about nine years after being diagnosed with HIV to start anti-HIV drug therapy. Experts now believe that the sooner after infection that treatment starts, the better chance the medications have of hampering the virus and keeping it from hiding and lying dormant in cells. The longer treatment is delayed, the greater the chance that HIV can also mutate to use CXCR4 and CCR5 to infect cells. That means the London patient may have HIV remaining that can use CXCR4 to infect cells, giving the virus a way to start flourishing again.

Can bone marrow transplants eliminate HIV for a large number of people?

“If you are saying that bone marrow transplants are now going to be a viable way to cure large numbers of people with HIV in a scalable way, the answer to that is absolutely not,” says Dr. Anthony Fauci, director of the National Institutes of Health’s National Institute of Allergy and Infectious Diseases. “Bone marrow transplants are risky. I would much rather be on one pill a day with relatively little toxicity than risk a bone marrow transplant so I don’t have to take one pill a day.”

Both Brown and the London patient underwent bone marrow transplants because they needed to treat their cancer, not to treat their HIV; and both experienced side effects of rejection at varying levels, since they received cells from an unrelated donor.

Fauci sees the report of the London patient as being less about the possible benefits of bone marrow transplants in treating or even curing HIV, and more about the need to focus HIV research on CCR5. Finding ways to treat people infected with HIV with some infusions of mutated CCR5 cells that block infection seems to make more sense now. These efforts include editing the CCR5 gene in HIV-positive people and giving the genetically edited cells back to them. Scientists have already used the gene editing tool CRISPR to snip out HIV in human cells in the lab, but they are still years away from proving the technology is safe to use in patients.

Still, Fauci is hopeful that such approaches will eventually be available for HIV patients. “So many things have happened that I thought were out of our realm of possibility,” he says. “So while it’s truly aspirational, I wouldn’t say it’s out of the realm of possibility.” Both Brown and the London patient are testament to how effective such strategies in modifying CCR5 can be in thwarting HIV.</s>A cell infected with HIV. Nearly 37 million people are living with HIV worldwide but only 59 per cent are receiving antiretroviral therapy Alamy

A British man known as the “London patient” has become the second adult in the world to be in sustained remission from HIV and could be cured.

Tests found no trace of the virus — which causes Aids — more than 18 months after the man came off the antiretroviral drugs he was using to manage the condition.

Doctors carried out a bone marrow transplant from a donor with a rare genetic mutation that confers resistance to the infection. It was a similar approach to that used on Timothy Brown, also known as the “Berlin patient”, who remains HIV-free today after treatment in Germany in 2007.

“By achieving remission in a second patient using a similar approach we have shown that the Berlin patient was…</s>LONDON — A second person has experienced sustained remission from HIV-1, according to a case study to be published Tuesday in the journal Nature. Effectively, some scientists believe that the “London patient” has been cured of the viral infection, which affects close to 37 million people worldwide.

The new case report comes more than 10 years after the first case, known as the “Berlin patient.” Both patients were treated with stem cell transplants from donors who carried a rare genetic mutation, known as CCR5-delta 32, that made them resistant to HIV. The London patient has been in remission for 18 months since he stopped taking antiretroviral drugs.

“By achieving remission in a second patient using a similar approach, we have shown that the Berlin Patient was not an anomaly and that it really was the treatment approaches that eliminated HIV in these two people,” said Ravindra Gupta, lead author of the study and a professor in University College London’s Division of Infection and Immunity.

Gupta added that the method used is not appropriate for all patients but offers hope for new treatment strategies, including gene therapies. He and his colleagues will continue to monitor the man’s condition, as it is still too early to say that he has been cured of HIV.

Almost 1 million people die annually from HIV-related causes. Treatment for HIV involves medications that suppress the virus, known as antiretroviral therapy, which people with HIV need to take for their entire lives.

Gupta’s patient, a male resident of the UK who prefers to remain anonymous, was diagnosed with HIV infection in 2003 and began antiretroviral therapy in 2012. Later, he was diagnosed with advanced Hodgkin’s lymphoma. After chemotherapy, he underwent a stem cell transplant in 2016 and subsequently remained on antiretroviral therapy for 16 months.

To test whether he was truly in HIV-1 remission, the London patient disrupted his usual antiretroviral therapy. He has now been in remission for 18 months, and regular testing has confirmed that his HIV viral load remains undetectable.

Similarly, Timothy Ray Brown, the Berlin Patient, had been living with HIV and routinely using antiretroviral therapy when he was diagnosed with a different disease, acute myeloid leukemia. After two bone marrow transplants, Brown was considered cured of his HIV-1 infection. Traces of HIV were seen in Brown’s blood a few years after he stopped antiretroviral therapy. However, because HIV remained undetectable, he is still considered clinically cured of his infection, according to his doctors.

Despite various attempts by scientists using the same approach, Brown had remained the only person cured of HIV until the new London patient.

‘We have a lot more work to go’

Dr. Sharon Lewin, director of the Peter Doherty Institute for Infection and Immunity and a professor of medicine at the University of Melbourne, said the long remission seen in the London patient is “exciting.”

“Coming 10 years after the successful report of the Berlin Patient, this new case confirms that bone marrow transplantation from a CCR5-negative donor can eliminate residual virus and stop any traces of virus from rebounding,” said Lewin, who was not involved in the new case study. “Two factors are likely at play: The new bone marrow is resistant to HIV, and also, the new bone marrow is actively eliminating any HIV-infected cells.”

Graham Cooke, a professor of infectious diseases at Imperial College London, said in a statement to the Science Media Centre that the new study is “encouraging.”

“If we can understand better why the procedure works in some patients and not others, we will be closer to our ultimate goal of curing HIV,” said Cooke, who was not involved in the case study. “At the moment the procedure still carries too much risk to be used in patients who are otherwise well, as daily tablet treatment for HIV is able to usually able to maintain patient’s long-term health.”

Dr. Timothy Henrich, an associate professor of medicine and physician scientist at University of California, San Francisco’s Department of Medicine, also noted that the London patient’s treatment “is not a scalable, safe or economically viable strategy to induce HIV remission.” For now, its use is restricted to those who need the transplant for other reasons, not for HIV alone, said Henrich, who was not involved in the new case study.

“There are actually many strategies right now that are currently being pursued,” Henrich said. “Some of them are directly related to the Berlin patient and work with transplantation: for example, gene modification therapy.”

“I am an optimist because I’m a scientist and vice versa,” Henrich said. “I do have hope. I think that finding a scalable cure that is safe and can be applied to a vast majority of individuals living with HIV is definitely attainable, but we have a lot more work to go.”
An HIV-positive man, identified as "the London patient", is the second known adult worldwide cleared of the HIV virus after a bone marrow transplant from an HIV-resistant donor. He has been in remission from HIV for 18 months and is no longer taking HIV drugs.