Update: 3 p.m. October 1: Timothy Ray Brown has died of leukemia, his partner Tim announced Tuesday on Facebook. He was 54.
A man identified only as the “London patient” has become the second person ever to be declared cured of HIV.
Researchers announced this week at the Conference on Retroviruses and Opportunistic Infections in Seattle that after receiving a bone marrow transplant from a donor with a known resistance to HIV, the man has been free of the virus for 18 months without medication. This has happened only once before, 12 years ago, using the same the treatment, though multiple other attempts between then and now have not been successful.
Scientists are hailing this as a triumph that may very well lead to a mainstream cure down the line, but they caution that this exact treatment is unlikely to have widespread applications. The treatment is very intense and is not considered appropriate for most people living with HIV.
There is also controversy over whether the word “cure” is accurate. The researchers involved in this case prefer to think about it as a long-term remission. Having replicated the original success, however, experts are calling this a “proof of concept” that medicine can rid the body of HIV.
One Success Followed by Years of Failure
The treatment was first used in 2007 with a man originally called the “Berlin patient” and later identified as Timothy Ray Brown, who had leukemia. Doctors suggested a stem cell transplant to cure the cancer. The idea is that the transplant would replace cells damaged by disease, infection, or chemotherapy with healthy cells from a donor, essentially allowing patients to rebuild their immune systems.
Before having a transplant, however, patients often need to receive chemotherapy or radiation to kill the existing cells. They’re also given drugs to suppress their immune system, so it does not attack the new cells. This can be very a difficult treatment especially for people who, like Brown, are already quite sick. He experienced many side effects from the treatment and was even put into a medically induced coma at one point.
What makes Brown’s treatment unique was that doctors used transplanted material from a donor known to have a genetic resistance to HIV in hopes that when his immune system was rebuilt with the new cells, it could fight off the virus. The resistance is the result of a genetic mutation called CCR5-delta 32, which occurs in small pockets of people throughout Europe and Asia. HIV attacks white blood cells, and most types of the virus are thought to attach to these cells through the CCR5 receptor. The mutation changes this receptor in such a way that it blocks HIV.
Brown, who is now 52, appears to be free of HIV. And though trace amounts of the virus have been found in his blood, none of it can replicate. The problem, however, is that no one quite knows why Brown was cured. Maybe the treatment worked exactly as doctors had hoped and allowed his body to build a new immune system that was both cancer-free and protective against HIV. It is also possible that the intense treatment he went through to prepare for the transplant helped rid his body of HIV. A third explanation is something called graft versus host disease, in which his new immune system attacked the remnants of his old one, including HIV. It could be a combination of the three or another unknown cause.
Some experts feared Brown’s cure was a fluke, and these fears intensified as attempt after attempt to replicate Brown’s success failed. In 2013, for example, Rewire News Group reported on the cases of two men in Boston who had Hodgkin’s lymphoma and received bone marrow transplants from donors with the mutation. The doctors were hopeful that their less intense treatment worked and announced a cure—prematurely. Within months, HIV was once again found in both men’s blood.
Another patient who had this treatment was later found to be infected with a form of HIV called X4, which uses a different receptor to enter cells. Doctors do not know whether he was infected with this type of the virus after the treatment or whether some patients harbor a small number of X4 viruses that start to multiply when other types of HIV are not present. Brown takes a daily medication to prevent infection with X4.
What the London patient adds to our knowledge
After so many failed attempts at replication, the London patient is giving researchers hope that Brown’s case was not just luck. The man, who has decided not to give his name to the press, was diagnosed with Hodgkin’s lymphoma, a cancer of the immune system that, in most cases detected early, can be cured. He was not as sick as Brown when he started the treatment, and the regimen he was given pre-transplant was not as harsh. He underwent treatment in 2016 and stopped taking antiretroviral medication the following year. Scientists have been monitoring his blood closely, and only one test in that time showed any traces of the virus; they suggest that result could be due to contamination of the test. He has now been HIV-free without medication for 18 months.
The London patient is one of 38 patients given bone marrow treatment, including six who used donors without the mutation, that a group of researchers is following. While the debate over whether to call it a cure continues, experts believe that the fact that Brown now has some company is good for the future of HIV research.
Dr. Annemarie Wensing, a virologist at the University Medical Center Utrecht in the Netherlands, told the New York Times that this second case provides hope: “This will inspire people that cure is not a dream. It’s reachable.” It is also initial evidence that a less rigorous version of the treatment could exist. Dr. Ravindra Gupta, a virologist at University College London and who presented the findings this week, also said: “Everybody believed after the Berlin patient that you needed to nearly die basically to cure HIV, but now maybe you don’t.”
Scientifically, the new success also confirms the importance of the CCR5, which will likely encourage researchers to keep studying this key receptor. This may lead to additional medication (there is already a drug that can mimic the mutation if taken daily), gene therapies, or vaccines that also target the receptor.
No immediate changes to HIV treatment or prevention
No matter how successful transplants are in the patients who need them, it’s unlikely they will ever be the primary way in which doctors treat people with HIV. The treatment is simply too harsh, and the risks are too great. Moreover, we have to remember that we already have so many of the tools we need to tackle the HIV epidemic.
Today’s antiretroviral therapies (ART) require fewer pills, have fewer side effects, and work better than their predecessors. Finding the right regimen and staying on it can make the virus undetectable in a person’s blood, meaning both that they stay healthy and that they cannot transmit the virus to other people. And pre-exposure prophylaxis (PrEP) is also 92 percent effective in preventing HIV among individuals at high-risk when the pill is taken daily.
At the same time we reach for a cure—which still seems a long way off—we can focus on making sure everyone gets tested for HIV regularly, takes PrEP if they are at high risk, or gets antiretroviral drugs if they have HIV.