“I think this is really quite significant. It shows the Berlin patient was not just a one-off, that this is a rational approach in limited circumstances,” said Daniel Kuritzkes, chief of infectious diseases at Brigham and Women’s Hospital, who was not involved in the study. “Nobody doubted the truth of the report with the Berlin patient, but it was one patient. And which of the many things that were done to him contributed to the apparent cure? It wasn’t clear this could be reproduced.”
Modern drug treatments for HIV have transformed an infection that was once a death sentence into a condition that can be managed long-term, if people adhere to a lifelong medication regimen. Of the 37 million people living with HIV worldwide, 21 million have access to therapy that can keep the virus in check. The quest for a true cure has continued, driven by the need in lower-income countries, where access to drug therapy is often less certain and strains of drug-resistant virus are a bigger problem.
The case was hailed by infectious disease specialists and President Trump as a major advance. On Twitter, Trump called it “such great news for so many.” But physicians cautioned that while the new case should inject fresh energy and funding into efforts to develop treatments that use lessons from the two cases to put HIV infection into long-term remission, techniques such as stem cell transplants — which are not readily available and carry severe side effects in comparison with standard HIV treatments — would not become the standard of care for people infected with the virus.
The London patient, infected with HIV and suffering from Hodgkin’s lymphoma, received bone marrow cells as part of his cancer treatment in 2016 from a donor who had a malfunctioning CCR5 gene. The gene is known to create a protein that is crucial for HIV to invade white blood cells. In September 2017, he stopped taking the drugs that had kept his virus in check for the previous five years.
“While it is too early to say with certainty that our patient is now cured of HIV, and doctors will continue to monitor his condition, the apparent success . . . offers hope in the search for a long-awaited cure for HIV/AIDS,” Eduardo Olavarria, a hematologist at Imperial College London, said in a statement. The study was led by Ravindra Gupta at University College London.
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The success helps doctors understand why other patients failed to see similar results. Brown had also received a transplant with nonfunctioning CCR5 genes. But a set of “Boston patients” who received stem cell transplants with functioning CCR5 genes also experienced marked reductions in the reservoir of HIV in their cells and were able to go without treatment for months, showing that the transplant itself played a role in knocking back the virus. Their temporary results also suggested that the aberrant gene was necessary for a sustained cure.
Despite efforts to repeat the remarkable Berlin results, researchers had failed for a decade — in part because the possibility of doing such transplants is rare and because of the success of modern HIV medications in controlling the infection. Stem cell transplants are risky and are attempted only when there is a clinical reason, such as cancer. Donors must be a genetic match to recipients, and very few people naturally carry two copies of the disabled CCR5 gene, which limits the number of potential transplants. Several patients who have received such transplants since Brown’s successful treatment have died of their underlying cancer, several HIV researchers noted.
The new patient means that Brown, who decided in 2010 to reveal his identity and tell his story, is no longer alone.
“I’m so happy, to have somebody join my family,” Brown told Post Reports. “It’s a very small family -- I’m the only person in it so far, well, until this patient.”
Although stem cell transplants are not a feasible therapy for most people with HIV, that does not diminish excitement about the new case in the research community, which has become interested in using gene therapy to disable the CCR5 gene by using other technologies, including the gene-editing technology CRISPR.
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“These new findings reaffirm our belief that there exists a proof of concept that HIV is curable,” International AIDS Society president Anton Pozniak said in a statement. “The hope is that this will eventually lead to a safe, cost-effective and easy strategy to achieve these results using gene technology or antibody techniques.”
The CCR5 gene was thrust into the international spotlight recently by the revelation that a Chinese scientist had attempted to edit human embryos to create the same gene deletion, with the hope of creating babies that were immune to HIV. The experiment, which is under investigation and does not appear to have succeeded at creating the desired deletion in twin girls, was widely condemned as unethical, a premature and reckless use of an unproven technology and medically unnecessary because of a multitude of other ways to prevent HIV transmission.
But researchers do hope that shutting down the CCR5 gene could offer a way to cure HIV in adults who are infected.
“I think that one thing we’ve learned is finding a scalable, economically feasible cure, or HIV remission, is going to be difficult,” said Timothy Henrich, an infectious disease specialist at the University of California at San Francisco not involved in the study. “It’s not going to be easy, and it’s not going to be quick. But I think that every year we get a little bit closer to the ultimate goal, and cases like this I hope will continue to excite and inform the community.”
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