Curing HIV: The audacious goal
Meanwhile, scientists at Fred Hutch and other institutions continue to explore ways to set a distant, yet even more audacious goal: to not just to stop HIV infection but cure it.
Sitting in the audience of the daylong Seattle workshop was Timothy Ray Brown, who remained — at that moment — the only person on Earth deemed to have been successfully cured of HIV.
[On Monday, word leaked that a second patient, treated with a blood stem cell transplant for Hodgkin lymphoma in London, is now likely to be the second person ever to be cured of HIV. The unnamed patient received stem cells from a donor carrying HIV resistance genes and has shown no signs of infection since he stopped taking antiviral drugs in September 2017.]
Efforts at Fred Hutch and other institutions to cure HIV by clearing out all traces of the virus have been inspired greatly by Brown, an HIV-positive man with leukemia who received two blood stem cell transplants to successfully cure his cancer — 12 years ago. A Seattle native, he was living in Berlin at the time, and his doctor sought out stem cell donors who carried a rare genetic mutation that naturally confers resistance to HIV.
Remarkably, the strategy worked, although up to now, only for him.
“I’ve been saying from the beginning that I have been doing this because I would like more people to join my ‘family,’" Brown said.
Dieffenbach’s talk focused on two approaches to curing HIV. One is to find ways to eradicate the last traces of HIV in the body. Brown’s transplant from a donor who carried two copies of the HIV resistance gene — from mother and father — is one example of that. Another way is to genetically engineer a patient’s immune cells to include those resistance traits — the kind of work underway at Fred Hutch.
A second approach is to focus on ways to give patients what he called “remission in absence of eradication.” In this case, the patient’s own immune system could be trained to block HIV whenever sleeping HIV-infected cells awaken and begin shedding virus. This might be accomplished through injections of HIV-blocking antibodies, like those being tested in vaccines.
“A therapeutic vaccine remains in some ways a holy grail,” he said. “The fantasy is to elicit a profound immune response that continues to drop DNA levels of virus present in an individual.”
In a series of lectures, speakers outlined other efforts to find a path to a cure:
- Dr. Joshua Schiffer from Fred Hutch described an approach that uses a low-cost, readily available immunosuppressant drug to slow down proliferation, the natural way immune cells increase their numbers. The drug, called mycophenolate mofetil, is normally used in transplants to prevent donated immune cells from attacking healthy tissues of the patient. In a small trial with HIV-positive patients, Schiffer’s team is testing whether it can knock down the proliferation of immune cells that might be harboring HIV genes from earlier infections. Stop the increase of these cells, and the inventory of those containing HIV genes would eventually die out, the thinking goes.
- Dr. Monique Nijhuis, of the University Medical Center of Utrecht, the Netherlands, described how European doctors have amassed a list of 22,000 potential stem cell transplant donors who carry HIV-resistant genes, like those received by Brown. That has enabled them to continue to test transplantation to eradicate HIV. The European consortium is analyzing the results of 39 patients who have received such transplants, 26 of whom are still alive.
One way or another, researchers are looking for a way to keep HIV at bay without the need for a lifetime of antiviral drugs. In other words, they want more Timothy Ray Browns.
During his talk on HIV cure research, Dieffenbach described the workshop as “an homage” to Brown. “There is still so much we can learn from Timothy and his case,” he said.
“For patients like Timothy, with cancer and HIV, cancer is the worst of the two,” Dieffenbach added. “His leukemia required a sledgehammer-like approach to get through his lethal cancer. … Congratulations, Timothy. It’s great to have you here on your 12th anniversary.”
[Editor's note: This story has been updated to reflect breaking news on March 4 that a second HIV-positive patient who received a blood stem cell transplant for cancer appears to be cured of HIV, 12 years after Brown went off antiviral medications.]