This image shows proteins on the HIV virus binding receptors on the T cell (source: National Institute of Allergy and Infectious Diseases, National Institute of Health)

 Doctors in Minnesota have performed a blood-forming stem cell transplant on a 12 year-old boy with both leukemia and HIV infection that could treat both the cancer and the infection (read more about the news here). The first person to receive such a transplant, Timothy Ray Brown (also known as “the Berlin patient”), has been free of HIV since his transplant in 2008. Brown’s transplant, and those of a handful of people since then, have all been from adult donors. The child in Minnesota received cord blood.

It’s big news, but this transplant and Brown’s before it aren’t the therapy that could become a widespread cure—there aren’t enough of the appropriate donors to treat everyone with the disease.

Instead, they prove the concept that HIV can be eradicated. Two groups in California, both funded by CIRM, are building on these transplants to generate therapies that could be used more broadly.

Here’s how the first two transplants worked. There’s a protein on the outside of T cells (the cells the HIV virus infects) that goes by the cumbersome name of CCR5. The HIV virus latches onto the protein as the first step to infecting the cell. Without CCR5, the virus can’t get in.

As luck would have it, a small number of people—mostly of northern European descent—have a mutation that results in a lack of functional CCR5. These people are naturally immune to HIV infection.

OK, so what does this have to do with stem cell transplants? Stem cells in the bone marrow and in cord blood contain blood-forming stem cells that create all the blood and immune cells of the body. When people with leukemia get a bone marrow transplant, they are also receiving these blood-forming stem cells from another person that rebuilds their blood and immune system. In the case of cancer, their new blood system is now cancer free.

But if that transplant comes from someone who has the CCR5 mutation, then the person’s new immune system will also be resistant to HIV. That’s how Timothy Ray Brown was cleared of his infection. Brown had leukemia and needed a bone marrow transplant, and he was also HIV positive. His doctors in Berlin found a donor who had the CCR5 mutation, and used bone marrow from that donor to cure Brown of both his leukemia and his HIV.

The boy who received the transplant in Minnesota has a similar story. In his case, his doctors found a cord blood donor who matched this patient, and that donor had the CCR5 mutation. That transplant is expected to both treat the boy’s leukemia and clear him of his HIV infection.

So, if the procedure works for this boy the way it did for Brown (and seems to have worked for other patients), why isn’t this the therapy for all people infected with HIV?

The problem is that the CCR5 mutation is rare. There’s unlikely to be enough people (or stored cord blood) with the mutation to be able to treat all HIV positive people.

Still, these cases do show that stem cells containing the CCR5 mutation have the possibility of treating the disease. And if the problem is a shortage of the appropriate stem cells then the answer is obvious: learn how the make stem cells with the mutation in the lab. Then there will be enough for everyone.

That’s the idea behind two disease teams we funded back in 2009. Both teams intend to take blood-forming stem cells out of the bone marrow of people infected with HIV. Then, they are going to alter those cells in the lab so that they carry the CCR5 mutation.

With that step, they create a source of stem cells that are matched to the patient (because they are the patient’s own cells) and that will be resistant to HIV. The doctors will then put those cells back into the patient where they will create a new blood and immune system that resists the infection. And voila! A source of therapeutic cells that doesn’t rely on the small number of people with the naturally occurring mutation.

The difference between our two teams lies in how they are creating the mutation. The end goal is the same, it’s just not clear which approach to creating the mutation will be most effective.

John Zaia, who leads the HIV/AIDS disease team at City of Hope, recently recorded this short description of his project:

Despite the groundbreaking nature of the science, Brown’s advice to the young boy before his procedure was routine. The Washington Blade reported him telling the boy:

“When I had my procedure done, I got caught up in the trap of lying around in my bed in the hospital watching television and not exercising. Make sure as soon as you are able, get out of bed and do some exercise, go do what you love, go play some basketball.”

Here’s more about CIRM’s funding commitments to HIV/AIDS and descriptions of the disease team projects: HIV/AIDS Fact Sheet.

A.A.