The Rise and Fall of the Boston Patients
A little over a year ago I first wrote about the Boston patients. These two men took us on an unusual journey this year. It began in 2010 when Timothy Henrich, then a fellow at Brigham and Women’s Hospital, was looking for a new research project. What he stumbled onto was a novel way of pursuing a cure for HIV. This week we learned that two men who were once considered as nearing a cure are actually not. Although it seems like this news should be a disappointing blow to the HIV research field, it actually gives us new insight into how to fight the virus.
Timothy Henrich was inspired by the story of Timothy Ray Brown. Timothy, suffering from acute myeloid leukemia, received a novel therapy that treated both his cancer and his HIV infection. He received two bone marrow transplants from a donor who was naturally resistant to HIV. This donor was resistant to HIV thanks to a mutation called CCR5Δ32. The CCR5 gene is almost always necessary for HIV to enter human cells. People missing 32 tiny bits of the gene have natural resistance to HIV because the virus can’t enter their cells.
Timothy received mutant cells that went on to make a brand new immune system in his body. This new immune system was one that HIV couldn’t invade. Stopping antiviral therapy in 2007, he has never gone back on the medication. This is called a functional cure. Timothy may have some virus hidden in his body but he remains off therapy; cured.
Henrich, starting a new research project, was interested in how Timothy’s cure worked. He wanted to understand how HIV hides in the body. Even if a person has been on antiviral therapy for decades with no detectable virus in their blood, once they stop taking drugs, the virus will return. Henrich wondered what role the bone marrow transplant Timothy received played in his cure. To test this he analyzed samples from two men who, like Brown, had cancer and HIV. Unlike Timothy, the bone marrow transplants they received were not CCR5Δ32 and therefore not resistant to HIV. Henrich wasn’t trying to cure anyone. So imagine his surprise when he found the samples he analyzed contained no hidden HIV. The results were announced at the AIDS 2012 conference to an excited crowd. After careful consideration, the team decided to take the two men, now named the Boston patients, off antiviral drugs. Could they, Henrich wondered, control the virus on their own just like Timothy?
The early results were promising. The virus seemed to be held at bay. The news was unprecedented and undeniably exciting. So it was a blow to learn this week that just 4-8 months after stopping therapy the virus came back. The Boston patients weren’t protected by the bone marrow transplants.
The news is disappointing-especially for these two men who may have briefly dreamed of a life without antiviral drugs. But for HIV research, the news is not a crushing blow; instead the returning virus gives us a new clue about how to cure the infection.
The news isn’t discouraging because bone marrow transplants were never the answer to curing HIV. Bone marrow transplants are dangerous procedures. Approximately 30% of people receiving a transplant from a donor do not survive. No researcher would give a person living with HIV a bone marrow transplant unless it was needed to treat their cancer. The Boston patients were never the answer to curing HIV. Instead, they’re the signposts on the path. Henrich wanted to know what role a bone marrow transplant played in Timothy Brown’s cure. We now can postulate that it wasn’t the transplant alone. This in itself is valuable. It rouses us to further support therapies based on genetic resistance to HIV. The rebounding virus inside these two men tells us the extent of how HIV hides in the body. It reveals the importance of pursuing gene therapy for HIV. Multiple clinical trials are looking at how to use gene therapy to create an immune system that makes the cells in the body look like CCR5Δ32-the mutation keeping the virus controlled in Timothy. They deserve our support more now than ever.
Although we never like hearing about a therapy that doesn’t work or when a virus returns, these cases tell us that when pursuing a cure, we are on the right path.