Stem-cell transplant seems to fend off HIV
A bone marrow transplant seems to have suppressed HIV virus levels in blood. These results have been observed in a single patient and have not yet been reported in the peer-reviewed literature. According to news reports, a man infected with the AIDS virus received a bone marrow transplant as part of leukemia treatment. The donor of the bone marrow was naturally resistant to HIV infection because of a mutation in the CCR5 protein that the virus uses to gain entry into the cells it infects. Afterwards, the patient stopped taking his AIDS drugs. Twenty months later, though they cannot conclude that the virus has been vanquished, doctors cannot find evidence of leukemia or HIV in the 42-year-old patient.
See the reports in Reuters (shorter) and the Wall Street Journal online (more detailed.)
But the doctors say that bone marrow transplants won't be used to treat HIV. In a bone marrow transplants, a patient’s own blood-forming stem cells are largely obliterated and then replaced. The painful procedure renders patients exhausted and extremely vulnerable to infection until the new stem cells take up residence in the bone marrow and restore the destroyed immune system.
The concept of supplying HIV patients with virus-resistant blood has been proposed before, mainly in the context of genetically engineering blood progenitors to resist the virus. Rather than genetically manipulating T-cells to prevent the virus from entering, the gene therapy trials I know about manipulate a patient's own cells to attack the virus once it begins replicating inside cells. (A search for "gene therapy" and "AIDS" on clinicatrials.gov pulls up over a dozen trials, including a Phase II trial from pharmaceutical giant Johnson and Johnson.)
One challenge for pursuing the strategy of gene therapy is that cells that like to grow in the blood and bone marrow don't adjust well to a culture dish. It can be hard to get hold of enough cells to manipulate. Nonetheless, talk of using blood-forming stem cells beyond curing leukemia is certainly proliferating. Besides this recent report on HIV, there is talk of co-transplanting blood-forming stem cells alongside cell therapies as a way to prevent a patients’ body from rejecting transplants. As far as I know, these are regulated to so-called natural experiments such as this one and there are no plans for human trials.
(See Protecting Cells from Immune Attack )
Comments
I think one thing needs to be cleared up in this spate of stories about this case--the doctors cannot find HIV in the patient's blood, but the patient is not "cured" of HIV. The approach prevents HIV from entering T cells, so it cannot infect and replicate in blood and the patient's viral load remains undetectable, just like an HIV patient successfully treated with antiretrovirals. One can be certain that HIV is still present in the patient's gut, lymph tissues and brain, among other places. HIV has integrated itself into the patient's DNA.
One other point of interest, Irvin Chen at UCLA, who is mentioned in the WSJ article and again today in the NYT, has received a disease team planning grant to pursue a CCR5 receptor deleting gene therapy approach--first with autologous stem cells, then potentially with HESCs and IPS cells. This case presents, as Dr. Baltimore noted, a nice proof of concept for the approach. It should be quite interesting to see the submission to CIRM this spring and to observe how the application is viewed.
Posted by: Jeff Sheehy | November 14, 2008 06:06 PM