CROI 2019: The case of the London patient adds validation to one approach towards a cure

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Science Speaks is in Seattle this week covering breaking news in HIV research, policies and plans at CROI 2019 March 4-7.

SEATTLE – If you’re counting those in lasting remission from HIV, Dr. John Mellors of the University of Pittsburgh said here today, there’s been a doubling in their numbers.

Now there are two.

The dry tone of Mellor’s remarks, and the circumspect wording of Dr. Ravindra Gupta, the physician researcher of University College London, who he introduced, stood in stark contrast to that of news headlines, which since the day before had touted the breakthrough of the London patient “cured” of HIV.

“Maybe temper the use of that word, whilst remaining positive,” Dr. Gupta said. He uses the word “remission,” as in the title of his talk to a packed room today: “Sustained HIV-1 Remission Following Homozygous CCR5 Delta 32 Allogenic HSCT.”

The scientists and the news reports agree on this: Ten years after Timothy Ray Brown, known then as “the Berlin patient,” became the first person ever to be considered cured of HIV, he has company that reaffirms the understanding that his case offered the HIV cure field. The news of that broke this week in the report of a man called “the London patient.” He was a man living with HIV who, like Mr. Brown, needed a stem cell transplant after multiple courses of chemotherapy failed to control cancer that he also was fighting, and who also got a transplant from a donor with a mutation that provides protection to people born with it from getting HIV. Now, like Mr. Brown, the London patient lives without antiretroviral treatment, and without any sign of viable, replicating HIV.

Mr. Brown himself is here, and everything he has been through has left him moving slowly for his 53 years, but he is beaming. He wouldn’t be here at all if he hadn’t had a second, grueling stem cell transplant, with effects so dire he spent a month in a medically induced coma, that finally worked to rid him of cancer. And he wouldn’t be at this particular conference, if the process, brutal as it was, hadn’t, also, apparently cured him of HIV. The facts of his case have long supported that is what happened. His physicians painstakingly sought a donor whose cells included a genetic mutation to the protein — the CCR5 protein — that keeps HIV from getting in. Because he was in Berlin, and the vast majority of the 10 percent of all people having that mutation are northern European, and because he was in Germany, where robust health services are readily accessible, a suitable donor match was found. And once the whole ordeal was over, he was over HIV — the first, and for 10 years, the last person to achieve the status of “former HIV patient.” He alone has served as proof of the concept that HIV could be cured.

He has been generously accessible to science, which has demanded multiple and microscopic examinations of his bodily tissues ever since. He is very pleased that another case has added validation to the knowledge that was gleaned through his case.

But while there were multiple reasons to believe it was the transplant, from the donor with the mutated gene, that cured him, there also were multiple reasons that success couldn’t be readily replicated. The most important was that the cure was worse than the disease — while stem cell transplants carry a 10-to-20 percent mortality rate, people controlling their HIV with antiretroviral medicine can live normal life spans without transmitting the virus. That, taken together with the relative rarity of needing a stem cell transplant, of finding the right donor, of surviving the experience, have stood in the way of saying the doctors who cured Timothy Ray Brown discovered a cure for HIV.

But they had shown that the CCR5 could ward off the virus even when moved into the body of someone with active HIV. With a stretch of the imagination, though, the possibility seemed to have remained that the chemotherapy, followed by the full body irradiation that Mr. Brown underwent helped kick out the virus. Or that he had some other unique characteristic, yet to be discovered. The London patient, sick with a different kind of cancer, when chemotherapy and stem cell transplant medicine has advanced, and who did not receive full body irradiation, makes those remote possibilities all the less likely, while his case may serve to spur support for research into how using the CCR5 mutation can lead, in some other way, to a cure.

And, Dr. Gupta said today, the London patient is healthy, doing well overall. Maybe, in another six months or year, he can be called cured, Dr. Gupta added.

At the end of his talk, an audience member noted that as Mr. Brown was in the room, “we can thank him,” and the audience packing the room applauded.

 

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