Let me start out by first making it clear that those involved with this study do NOT believe this is a "cure" for AIDS (for some reasons I'll get into in a bit). However, one of the researchers involved called the case that was just published in the New England Journal of Medicine, a "flicker of hope" that something better might be on the horizon in the form of gene therapy.
Last November it was first reported that a a 42-year-old male HIV patient with leukemia had been given a transplant of bone marrow stem cells from a donor carrying a genetic mutation called CCR5-Δ32. Two years after the transplant, the patient continues to have no symptoms or a detectable presence of the HIV virus in his body.
From CNN:
"The patient is fine," said Dr. Gero Hutter of Charite Universitatsmedizin Berlin in Germany. "Today, two years after his transplantation, he is still without any signs of HIV disease and without antiretroviral medication."
The case was first reported in November, and the new report is the first official publication of the case in a medical journal. Hutter and a team of medical professionals performed the stem cell transplant on the patient, an American living in Germany, to treat the man's leukemia, not the HIV itself.
However, the team deliberately chose a compatible donor who has a naturally occurring gene mutation that confers resistance to HIV. The mutation cripples a receptor known as CCR5, which is normally found on the surface of T cells, the type of immune system cells attacked by HIV.
The way HIV-1 (the most common form of the HIV virus) attacks the human immune system is by binding onto T-cells at the CD4 & CCR5 receptors. With CCR5-Δ32 (chemokine receptor 5, 32 base-pair deletion), it's a deletion mutation that causes a non-functional receptor, preventing expression of the receptor on the cell surface. The HIV virus can't latch on, and thus can't infect the cells. If a person has one copy of the CCR5-Δ32 allele, it can offer some resistance to, or slow down the progression of the virus. If both copies are present (one from each parent), a person theoretically has a natural immunity to HIV-1.
The origin of the CCR5-Δ32 mutation has been studied and hypothesized about for a while. The mutation is largely found only in a very small percentage of people from European descent. This has led to theories the selective pressure in its development might of been Smallpox, and the mutation a product of its aftermath, since it's thought CCR5-Δ32 should offer protection from Smallpox as well (let's hope we never have to test that theory).
Now, why did I say this transplant is NOT a cure?
While promising, the treatment is unlikely to help the vast majority of people infected with HIV, said Dr. Jay Levy, a professor at the University of California San Francisco, who wrote an editorial accompanying the study. A stem cell transplant is too extreme and too dangerous to be used as a routine treatment, he said.
"About a third of the people die [during such transplants], so it's just too much of a risk," Levy said. To perform a stem cell transplant, doctors intentionally destroy a patient's immune system, leaving the patient vulnerable to infection, and then reintroduce a donor's stem cells (which are from either bone marrow or blood) in an effort to establish a new, healthy immune system.
Also.....
- While tests might not show the presence of the HIV virus in the transplant patient, that doesn't mean it's not there. "This type of virus can infect macrophages (another type of white blood cell that expresses CCR5) and other cells, like the brain cells, and it could live a lifetime. But if it can't spread, you never see it-- but it's there and it could do some damage,"
- Even if we could be sure the transplant would eliminate the HIV virus in its totality, the odds of finding compatible bone marrow donors with both copies of the mutation for the more than 30 million people infected with HIV are almost impossible. The mutation is almost non-existent in African & Asian populations.
So why might this be a "
flicker of hope"? It's more proof of concept that blocking the CCR5 receptor inhibits infection. Also, there are "
entry inhibitor" drugs that are coming into use to block the CCR5 receptor, like
Maraviroc (brand-named Selzentry), that will be taken in concert with anti-retrovirals.
Also, very smart people are working on the development of gene therapy to achieve the same effect as the transplant.
The results of the experiment may point researchers to a new way of controlling the AIDS virus HIV that doesn’t force patients to take drugs for the rest of their lives. Scientists will now intensify their search for therapies that achieve the same effect, predicted Jay Levy, a University of California, San Francisco, AIDS researcher.
"I think this article is going to stimulate a lot of companies to put more emphasis on gene therapy," Levy said yesterday in a telephone interview. He wasn’t involved in the research and wrote an editorial published today that accompanied the study.
One such trial sponsored by Sangamo Biosciences of Richmond, California, recently began at the University of Pennsylvania. It will test a gene therapy that aims to modify the immune cells in 12 patients infected with HIV so they lack the CCR5 receptor.