Wednesday, March 6, 2019

London patient may be second in world to be cured of HIV
Milestone From Bone-Marrow Transplant Shows Cure’s Possible


Apoorva Mandavilli

06.03.2019

For just the second time since the global epidemic began, a patient appears to have been cured of infection with HIV, the virus that causes AIDS. The news comes nearly 12 years to the day after the first patient known to be cured, a feat that researchers have long tried, and failed, to duplicate. The surprise success now confirms that a cure for HIV infection is possible, if difficult, researchers said.

The report is to be published on Tuesday in the journal ‘Nature’ and investigators to present some of the details at the Conference on Retroviruses and Opportunistic Infections in Seattle.

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

Both milestones resulted from bone-marrow transplants given to infected patients. But the transplants were intended to treat cancer in the patients, not HIV.

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

But rearming the body with immune cells similarly modified to resist HIV might well succeed as a practical treatment, experts said.

“This will inspire people that cure is not a dream,” said Dr Annemarie Wensing, a virologist at the University Medical Center Utrecht in the Netherlands. “It’s reachable.”Dr. Wensing is co-leader of IciStem, a consortium of European scientists studying stem cell transplants to treat HIV infection. The consortium is supported by AMFAR, the American AIDS research organization.The new patient has chosen to remain anonymous, and the scientists referred to him only as the “London patient.”

“I feel a sense of responsibility to help the doctors understand how it happened so they can develop the science,” he told The New York Times in an email. Learning that he could be cured of both cancer and HIV infection was “surreal” and “overwhelming,” he added. “I never thought that there would be a cure during my lifetime.”

At the same conference in 2007, a German doctor described the first such cure 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 gained little attention. Once it became clear that Brown was cured, scientists set out to duplicate his result with other cancer patients infected with HIV.

In case after case, the virus came roaring back, often around nine months after the patients stopped taking antiretroviral drugs, or else the patients died of cancer. The failures left scientists wondering whether Brown’s cure would remain a fluke. Brown had had leukemia, and after chemotherapy failed to stop it, he needed two bone-marrow transplants. The transplants were from a donor with a mutation in a protein called CCR5, which rests on the surface of certain immune cells. HIV uses the protein to enter those cells but cannot latch on to the mutated version.

Mr. Brown was given harsh immunosuppressive drugs of a kind that are no longer used, and suffered intense complications for months after the transplant. He was placed in an induced coma at one point and nearly died.

“He was really beaten up by the whole procedure,” said Dr. Steven Deeks, an AIDS expert at the University of California, San Francisco, who has treated Mr. Brown. “And so we’ve always wondered whether all that conditioning, a massive amount of destruction to his immune system, explained why Timothy was cured but no one else.”

The London patient has answered that question: A near-death experience is not required for the procedure to work. He had Hodgkin’s lymphoma and received a bonemarrow transplant from a donor with the CCR5 mutation in May 2016. He, too, received immunosuppressive drugs, but the treatment was much less intense, in line with current standards for transplant patients.

He quit taking anti-HIV drugs in September 2017, making him the first patient since Brown known to remain virus-free for over a year after stopping.

“I think this does change the game a little bit,” said Dr. Ravindra Gupta, a virologist at University College London who presented the findings at the Seattle meeting. “Everybody believed after the Berlin patient that you needed to nearly die basically to cure HIV, but now you don’t,” said Ravindra Gupta, a virologist at University College London.

Although the London patient was not as ill as Brown had been after the transplant, the procedure worked about as well: The transplant destroyed the cancer without harmful side effects.

So far, scientists are tracking 38 HIV-infected people who have received bone-marrow transplants, including six from donors without the mutation. The London patient is 36 on this list. Number 19 on the list, referred to as the “Düsseldorf patient,” has been off anti-HIV drugs for four months. Details of that case will be presented at the Seattle conference later this week.

The consortium’s scientists have repeatedly analysed the London patient’s blood for signs of the virus. They saw a weak indication of continued infection in one of 24 tests, but say this may be the result of contamination in the sample.

The most sensitive test did not find any circulating virus. Antibodies to HIV were still present in his blood, but their levels declined, in a trajectory similar to that seen in Brown. None of this guarantees that the London patient is forever out of the woods, but the similarities to Brown’s recovery offer reason for optimism, Gupta said. NYT



Scientists have long tried to duplicate the procedure that led to the first long-term remission 12 years ago

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