H.I.V. It is reported healed in a second patient, a milestone in the global AIDS epidemic


Only for the second time since the onset of the global epidemic, a patient appears to have recovered from H.I.V. infection, the virus that causes AIDS.

The news comes almost 12 years after the first patient known to be cured, a venture that researchers have long tried, and failed, to duplicate. The surprise success now confirms that a cure for H.I.V. The infection is possible, if difficult, the researchers said.

Investigators will publish their report on Tuesday in the journal Nature and present some details at the Conference on Retroviruses and Opportunistic Infections in Seattle.

Publicly, scientists are describing the case as a long-term remission. In interviews, most experts call it a cure, with the caveat that it is difficult to know how to define the word when there are only two known instances.

Both milestones are the result of bone marrow transplants administered to infected patients. But the transplants were intended to treat cancer in patients, not H.I.V.

Bone marrow transplantation is unlikely to be a realistic treatment option in the near future. Powerful drugs are now available to control H.I.V. infection, while transplants are risky, with harsh side effects that can last for years.

But rearming the body with immune cells similarly modified to resist HI.V. it could be successful as a practical treatment, experts say.

"This will inspire people that care is not a dream," said Dr. Annemarie Wensing, virologist at the University Medical Center in Utrecht, the Netherlands. "It is reachable."

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Dr. Wensing is co-leader of IciStem, a consortium of European scientists studying stem cell transplants to treat H.I.V. infection. The consortium is supported by AMFAR, the American organization of research on AIDS.

The new patient chose to remain anonymous, and the scientists referred to him only as the "London patient".

"I feel a sense of responsibility to help doctors understand how it happened so they can develop science," he told the New York Times in an email

Learning that it could be cured both by cancer and I.V. the infection was "surreal" and "overwhelming", he added. "I never thought there would be a cure during my life."

At the same conference in 2007, a German doctor described the first of these treatments in the "Berlin patient", later identified as Timothy Ray Brown, 52, who now lives in Palm Springs, California.

That news, displayed on a poster at the back of a conference room, initially received little attention. Once it became clear that Mr. Brown was healed, the scientists decided to duplicate his result with other cancer patients infected with H.I.V.

In any case, the virus roared, often around nine months after the patients had stopped taking antiretroviral drugs, or patients died of cancer. The failures left the scientists wondering if Mr. Brown's care would remain a stroke of luck.

Mr. Brown had had leukemia and, after chemotherapy could not stop it, he needed two bone marrow transplants.

The transplants came from a donor with a mutation in a protein called CCR5, which rests on the surface of some immune cells. H.I.V. uses the protein to enter those cells but can not cling to the mutated version.

Mr. Brown has been given hard immunosuppressive drugs of a type that are no longer used and have suffered from intense complications for months after transplantation. He was put in a coma induced at a certain point and almost dead.

"He was really beaten by the whole procedure," said Dr. Steven Deeks, an AIDS expert at the University of California, San Francisco, who treated Mr. Brown. "And so we always wondered if all that conditioning, a massive destruction of his immune system, explained why Timothy was healed, but no one else."

The London patient answered this question: a near-death experience is not required for the proper functioning of the procedure.

He had Hodgkin's lymphoma and in May 2016 he received a bone marrow transplant from a donor with the CCR5 mutation. He also received immunosuppressive drugs, but treatment was much less intense, in line with current standards for transplant patients.

He stopped taking anti-H.I.V. drug in September 2017, making him the first patient since Mr. Brown has been able to remain virus-free for more than a year after arrest.

"I think this changes a little bit the game," said Dr. Ravindra Gupta, a virologist at University College London who presented the results of the Seattle meeting. "Everyone believed after the Berlin patient that you almost needed to die to recover from I.V., but now maybe you do not."

"In a sense, the only person to compare directly is the Berlin patient, "he said." This is the only standard we have at the moment. "

Most experts who know the details agree that the new case seems a legitimate cure, but some are uncertain about its relevance for the treatment of AIDS in general.

"I'm not sure what this tells us," said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. "It was done with Timothy Ray Brown, and now here's another case – ok, so now? Now where do we go with it?"

One possibility, said Dr. Deeks and others, is to develop gene therapy approaches to break down CCR5 on immune cells or their predecessor stem cells. Resistant to H.I.V. infection, these modified cells should eventually eliminate the body from the virus.

(CCR5 is the protein that He Jiankui, a scientist in China, claimed to have modified with the gene editing in at least two children, in an attempt to make them resistant to HI.V. – an experiment that triggered international condemnation. )

Several companies are pursuing gene therapy but have not yet succeeded. The change should target the right number of cells, in the right place – just the bone marrow, for example, and not the brain – and modify only the genes that direct the production of CCR5.

"There are a number of levels of precision that must be achieved," said Dr. Mike McCune, senior global health advisor at the Bill and Melinda Gates Foundation. "There are also concerns that you can do something unpleasant, and if so, you may wish to have a kill switch."

Several teams are working on all these obstacles, said dr. McCune. In the end, they may be able to develop a viral delivery system that, when injected into the body, looks for all CCR5 receptors and eliminates them, or even a donor stem cell resistant to H.I.V. but it could be given to any patient.

"These are dreams, right? Things on the drawing board," said Dr. McCune. "These dreams are motivated by cases like this – it helps us to imagine what could be done in the future."

An important warning to any such approach is that the patient would still be vulnerable to a form of H.I.V. called X4, which employs a different protein, CXCR4, to enter cells.

"It will only work if someone has a virus that only uses CCR5 for entry – and this is probably about 50% of people living with HIV, if not less," said Dr. Timothy J. Henrich, an AIDS Specialist at the University of California, San Francisco.

Even if a person hosts only a small number of X4 viruses, they can multiply in the absence of competition from their viral cousins. There is at least a reported case of an individual who got a transplant from a delta 32 donor, but then rebounded with the X4 virus. (As a precaution against X4, Mr. Brown is taking a daily pill to prevent H.I.V. infection.)

Mr. Brown says he is confident that the care of the London patient is as lasting as his. "If something happened once in medical science, it can happen again," Brown said. "I've been waiting for the company for a long time."


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