Cure HIV with a Bone Marrow Transplant?

Nov 14th, 2008 | By | Category: Lit Round-up

From the respected medical journal…err the Wall Street Journal:

The startling case of an AIDS patient who underwent a bone marrow transplant to treat leukemia is stirring new hope that gene-therapy strategies on the far edges of AIDS research might someday cure the disease.

The patient, a 42-year-old American living in Berlin, is still recovering from his leukemia therapy, but he appears to have won his battle with AIDS. Doctors have not been able to detect the virus in his blood for more than 600 days, despite his having ceased all conventional AIDS medication. Normally when a patient stops taking AIDS drugs, the virus stampedes through the body within weeks, or days….

The breakthrough appears to be that Dr. Hütter, a soft-spoken hematologist who isn’t an AIDS specialist, deliberately replaced the patient’s bone marrow cells with those from a donor who has a naturally occurring genetic mutation that renders his cells immune to almost all strains of HIV, the virus that causes AIDS.

This story has received much media attention.

Here’s the big concept. The cells in your immune system that voraciously gobble up invaders, macrophages, have a protein on their surface called CCR5. CCR stands for chemokine receptor. Chemokines and chemokine receptors are how your immune cells talk to one another when fending off an invasion–a cellular game
of Marco-Polo.

Macrophages are constantly crawling all over your body, including just below the skin. When you have sex with an HIV positive individual, some of their virus can enter your body–through mucous membranes or small cuts in the skin. Your macrophages dutifully chase after the invading virus. When they meet, the virus turns tables on the macrophage–using the viral gp120 protein as a key to open up the CCR5 protein, using it as a door into the cell. Once safely inside the macrophage, the HIV virus can produce billions of copies of itself, per day per cell. Macrophages are hardy cells. They easily survive, even while pumping out virus.

In other words, the HIV gp120 protein in Rick Moranis, the macrophage’s CCR5 protein in Sigourney Weaver. Putting the two of them together? Extremely dangerous.

Eventually, the virus gp120 protein mutates until it can open the CXCR5 protein on the surface of CD4+ helper T cells (the generals of your immune system) like it opened the CCR5 protein on the macrophages. When this happens, the virus can efficiently enter into the T cells. These cells are much weaker than the macrophages, and die off when stressed by being forced to produce new virus copies. When enough T cells die off, you have AIDS.

About 1% of the population, thanks to having two mutant copies of the gene, completely lack the CCR5 protein. With no CCR5 protein, there is no way for the HIV virus to enter macrophages. Thus, these people are immune to HIV infection. Somewhere around 10-15% of the population has one bad copy of the CCR5 gene, and therefore have delayed progression to AIDS, as their macrophages are more resistant to infection than those with two good copies of the gene.


The bone marrow makes all the cells in the blood. If you have a blood cancer, the last ditch treatment is to kill off your (cancerous) bone marrow, and replace it with bone marrow from a healthy donor. The patient described in the article had leukemia (blood cancer) and was HIV positive. To treat his leukemia, his bone marrow was killed off. His donor marrow was mutant for CCR5. Now six hundred days after receiving the CCR5-lacking bone marrow, his doctors cannot detect HIV virus in his blood–even though the patient is no longer on drug treatment for HIV.

As much as I respect the awesome power of Rupert Murdoch and the Wall Street Journal, I’d like to see some of the claims here undergo a bit of scrutiny, as they would if published in a proper medical journal.

This is a case report, of an experience in a single patient. I’m loathe to declare that since “[d]octors have not been able to detect the virus in his blood for more than 600 days” this patient is cured from AIDS, let alone consider this as proof that transplantation of CCR5 mutant bone marrow will cure everyone with HIV of the infection.

If this is generally true–transplantation with CCR5 lacking bone marrow can “cure” you of HIV infection–big, but solvable, problems remain.

First, donors lacking CCR5 are rare–about 1% of the population. And it’s already difficult to find CCR5 normal bone marrow that is a close enough match to transplant. This could potentially be solved by using gene knockdown, to turn off the normal CCR5 genes most donor bone marrow contains.

The bigger problem is, undergoing a bone marrow transplant is both dangerous an unpleasant. The first step? A lethal dose of irradiation. If the bone marrow transplant doesn’t work, you die. Horribly. If the bone marrow takes, but then starts attacking your body, you die even more horribly. If it works perfectly, you’re still at a heightened risk of a whole slew of cancers, thanks to all the irradiation.

I’d stick with drug therapy, if given the choice.