Ten years after the Berlin patient, doctors announce a second person has been effectively cured of HIV
By Kate Sheridan <https://www.statnews.com/staff/kate-sheridan/> @sheridan_kate <https://twitter.com/sheridan_kate> March 4, 2019 Timothy Ray Brown (L), also known as The Berlin Patient, considered the first person to be cured of HIV. GERARD JULIEN/AFP/GettyImages For the second time, doctors appear to have put HIV into sustained remission with a stem cell transplant effectively curing the recipient. Their work, which was published in Nature and will be presented at the annual Conference on Retroviruses and Opportunistic Infections in Seattle on Tuesday, may encourage scientists working on new gene therapies based on similar principles and give hope to those living with the infection. The case comes nearly 10 years after Timothy Ray Brown announced he was the so-called Berlin Patient the first person who was functionally cured of HIV and able to stop taking antiretroviral drugs after an intensive round of chemotherapy and radiation and two bone marrow transplants. The person who received this latest transplant in London has not taken antiretroviral drugs since September 2017; he is not identified in the paper. Those of us in the field have been waiting for a second cure via this approach, said Dr. Keith Jerome, one of the leaders of HIV cure research at the Fred Hutchinson Cancer Research Center. As long as Timothy Brown was the only [one], wed have always wondered if there something unique about it. Jerome was not involved in the research published Tuesday. The researchers behind the paper are from an array of British, Spanish, Dutch and Singaporean institutions; the lead author is Ravindra K. Gupta <https://www.ucl.ac.uk/infection-immunity/people/professor-ravindra-gupta> 1, who is affiliated with the University of Cambridge, Imperial College London, and University College London. Experts caution that this news should not be interpreted as having found a cure for everyone with HIV. It doesnt change things for the average person with HIV right now, said Dr. Bruce Walker, the director of the Ragon Institute <http://www.ragoninstitute.org/> 3, a research institute affiliated with Massachusetts General Hospital, Harvard, and MIT that specializes in HIV/AIDS and infectious diseases. (Walker was also uninvolved with the Nature research.) It does change things in terms of the research agenda, because it further indicates that this is a potentially viable pathway forward to achieve a cure. That potentially viable pathway runs through a receptor called CCR5. CCR5 is one of a handful of receptors that HIV can use to get into a particular kind of cell. Those cells, called CD4-positive T-cells, are vital to a persons immune system. You can sort of think of [these] cells as the generals that are helping to orchestrate an effective defense, Walker said. If theyre not there, things tend to go haywire. Some people have a particular mutation in the genes that encode the CCR5 receptor that prevents the HIV virus from using it to get in to these T-cells and no entry means no infection. The person whose case is described in Tuesdays paper got a transplant of the stem cells that produce blood and immune system cells typically found in a persons bone marrow with this mutation from a donor; about 10 percent of people <https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.00303 39> 6 in some Northern European countries naturally carry the mutation. Like Timothy Brown, this persons transplant happened as part of his cancer treatment. After doctors diagnosed him with an advanced case of Hodgkins lymphoma, the person went through chemotherapy and a transplant from a donor picked in part for his or her CCR5 mutation. Unlike Brown, though, this persons cancer treatment didnt involve full-body radiation, and his chemotherapy was also far gentler. Thats encouraging, but Walker, the Ragon researcher, noted the risks from even this regimen were still too great to offer these kind of stem cell transplants outside of cancer treatment. Given that the life expectancy for people with HIV on antiretroviral medications has increased dramatically and, one study found <https://www.statnews.com/2017/05/10/hiv-life-expectancy-study/> 7, is now a nearly normal one, theres a very high bar for subjecting people to any additional risk, he said. This wasnt without risk, but was much less [risky]. The CCR5 mutations virus-blocking power can be simulated with a drug. Since 2007, Viiv Healthcare, a joint venture initially formed by Pfizer and GlaxoSmithKline, has marketed a drug, called Selzentry in the United States, that prevents HIV from using the CCR5 receptor by binding to the receptor itself. But that drug has the same issues that most drugs have: it needs to be taken every day. Just like any other suppressive therapy for HIV, as soon as a person stops taking the drug, the virus comes roaring back, said Fred Hutchinsons Jerome. In an ideal world, the treatment for HIV would look more like Luxturna, a recently approved gene therapy for a form of blindness that <https://www.statnews.com/2018/03/21/gene-therapy-luxturna-launch/> s injected just once9 into a persons eye, and less like Lipitor. The beauty of a transplantation or a gene therapy approach targeting CCR5 thats the kind of thing that looks like you can do it once, and then the persons cured, Jerome said. They dont need to worry about the virus any more, they dont need to worry about their access to drugs or remembering to take it every day. The most infamous gene therapy experiment targeting CCR5 is undoubtedly He Jiankuis, which created human embryos <https://www.statnews.com/2018/11/26/claim-of-crispred-baby-girls-stuns-geno me-editing-summit/> 10 and, later, actual children with a CRISPR-mutated CCR5 gene. His announcement triggered a massive backlash from scientists, ethicists <https://www.statnews.com/2019/01/24/crispr-babies-show-need-for-more-specif ic-rules/> 11, and the Chinese government <https://www.statnews.com/2019/02/25/crispr-babies-study-china-government-fu nding/> 12. Less controversial gene editing work is ongoing, too. Sangamo Therapeutics, for example, is working on genetically editing T-cells and stem cells <https://www.sangamo.com/pipeline> 13 to carry the CCR5 mutation. According to the companys pipeline chart, that treatment is in early-stage clinical trials. Tuesdays paper and the concept of using CCR5 as the basis for future treatments comes with caveats. For one thing, not all HIV viruses use CCR5 receptors to get into a cell; viruses that use other co-receptors exist, though theyre rarer. And even if a treatment can stop the virus from infecting new cells, it tends to linger in previously infected ones. The virus may still be hiding out someplace and it may come back 10 years from now, Walker noted. You can never be absolutely certain that a cure has been achieved. But to Jerome, the Fred Hutchinson Cancer Research Center researcher, a new report of even an uncertain cure is meaningful. Its a reminder about how difficult this challenge is and how difficult this virus is to deal with, but at the same time, it provides hope, he said. Now theres not one, but two people that others living with HIV can look toward for encouragement, he added. Kate Sheridan <https://www.statnews.com/staff/kate-sheridan/> General Assignment Reporter Kate is a general assignment reporter. 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