Man appears free of HIV after stem cell transplant
Updated 4:51 p.m. EST, Wed February 11, 2009
By Jacquelyne Froeber
A 42-year-old HIV patient with leukemia appears to have no detectable HIV in his blood and no symptoms after a stem cell transplant from a donor carrying a gene mutation that confers natural resistance to the virus that causes AIDS, according to a report published Wednesday in the New England Journal of Medicine.
"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 mutation is known as CCR5 delta32 and is found in 1 percent to 3 percent of white populations of European descent.
HIV uses the CCR5 as a co-receptor (in addition to CD4 receptors) to latch on to and ultimately destroy immune system cells. Since the virus can't gain a foothold on cells that lack CCR5, people who have the mutation have natural protection. (There are other, less common HIV strains that use different co-receptors.)
People who inherit one copy of CCR5 delta32 take longer to get sick or develop AIDS if infected with HIV. People with two copies (one from each parent) may not become infected at all. The stem cell donor had two copies.
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.
Levy also said it's unlikely that the transplant truly cured the patient in this study. HIV can infect many other types of cells and may be hiding out in the patient's body to resurface at a later time, he said.
"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," he said. "It's not the kind of approach that you could say, 'I've cured you.' I've eliminated the virus from your body." Health.com: 10 questions to ask a new partner before having sex
Before undergoing the transplant, the patient was also found to be infected with low levels of a type of HIV known as X4, which does not use the CCR5 receptor to infect cells. So it would seem that this virus would still be able to grow and damage immune cells in his body. However, following the transplant, signs of leukemia and HIV were absent.
"There is no really conclusive explanation why we didn't observe any rebound of HIV," Hutter said. "This finding is very surprising."
Hutter noted that one year ago, the patient had a relapse of leukemia and a second transplant from the same donor. The patient experienced complications from the procedure, including temporary liver problems and kidney failure, but they were not unusual and may occur in HIV-negative patients, he said.
Researchers including Hutter agree that the technique should not be used to treat HIV alone. "Some people may say, 'I want to do it,'" said Levy. A more logical -- and potentially safer -- approach would be to develop some type of CCR5-disabling gene therapy or treatment that could be directly injected into the body, said Levy.
Less invasive options to alter CCR5 could be on the horizon within the next five years, said Levy. "It's definitely the wave of the future," he said. "As we continue to follow this one patient, we will learn a lot."
One drug that's currently on the market that blocks CCR5 is called maraviroc (Selzentry). It was first approved in 2007 and is used in combination with other antiretroviral drugs. Health.com: Who's most at risk for STDs?
In 2007, an estimated 2 million people died from AIDS, and 2.7 million people contracted HIV. More than 15 million women are infected worldwide. HIV/AIDS can be transmitted through sexual intercourse, sharing needles, pregnancy, breast-feeding, and/or blood transfusions with an infected person.
"For HIV patients, this report is an important flicker of hope that antiretroviral therapy like HAART [highly active antiretroviral therapy] is not the endpoint of medical research," Hutter said.
Not the cure for AIDS
November 14, 2008
By Miriam Falco
CNN Medical Managing Editor
A German hospital announced this week that a 42-year old American living in Berlin who did not want to be identified had come to them three years ago for treatment. It was determined that he had acute leukemia (blood cancer) and was HIV positive too.
After a bone marrow transplant, it appears that not only did the man’s cancer go away, so did the virus that causes AIDS. This has been reported worldwide as a “cure” for AIDS. But even the doctors involved in this case say they don’t know if they cured this man of HIV. So what’s all the fuss about? Should HIV patients be treated with a bone marrow transplant?
One of America’s top AIDS expert doesn’t think so. “This is interesting but not a practical application. It’s not feasible and has extraordinarily limited practical application” long-time AIDS researcher and Director of the National Institute of Allergy and Infectious Diseases Dr. Anthony Fauci told CNN. He and other researchers first learned of this case back in February. But this study of one patient has not yet been published or been reviewed by other AIDS experts. It didn’t get much attention back then because of the many limitations it has. Dr. Robert Gallo is one of the scientists who discovered HIV. “While this procedure might help a very small minority of people living with AIDS,” Gallo says, “it is by no means the answer to the world’s HIV/AIDS pandemic.”
Doctors first began treating the cancer with chemotherapy. They also gave him anti-retrovirals to contain the virus that causes AIDS. Doctors said at a press conference this week that the patient did go into remission, but eventually the cancer came back. The next step to treat the cancer was a bone marrow transplant, which is common for leukemia patients.
His doctors emphasized that without further treatment, without the bone marrow transplant, he would have died of cancer - not HIV or AIDS.
But the patient’s physician, Dr. Gero Huetter, wanted to combine the cancer treatment with something he had heard about in medical school 12 years ago. That’s when researchers found out that a certain genetic mutation prevents the virus from getting into a person’s cells. But to be resistant to HIV, one has to have inherited this mutation from both parents.
So when it came to looking for a bone marrow donor for his patient, Huetter decided to see if he could find a donor that not only was a marrow match for his patient, but one who also had these two copies of the genetic mutation to see if they would get the bonus of treating the HIV, while treating the more urgent need - cancer.
Here’s where the German doctors admit they were very lucky. They told reporters they normally find one to five qualified donors for their patients in need of a transplant. In this case they found 80 donors. So they systematically tested each donor for the mutation and when they came to the 61st potential donor they hit the jackpot. Nearly two years after the bone marrow transplant, the patient is still in remission from his cancer and he doesn’t seem to have any detectable HIV either.
This is probably why many newspaper headlines interpreted the success as being a cure.
However there are many caveats to this story.
1. Even though their tests do not show a presence of HIV in his system, doesn’t mean it’s not there. This virus is known for hiding well and popping up later. It’s been seen before in patients taking anti-retroviral drugs. It is possible that if more sophisticated tests were used on this patient, they would detect the virus that is still in his body. So it’s still not entirely clear that he is HIV-free.
2. The chances of finding a bone marrow donor with two copies of this genetic mutation for everyone one of the 33 million people worldwide living with HIV or AIDS is not realistic because only one percent of Caucasians and zero percent of African Americans or Asians have this particular genetic mutation.
3. Bone marrow transplants are dangerous for patients. Before they can get the donated stem cells that will replace their own, they have to take strong chemotherapy to destroy their own bone marrow — leaving them without an immune system to fight off any disease — until the transplanted bone marrow can make new blood cells. Plus patients run the risk of rejecting the new cells, which means they have to take immune-suppressing drugs for the rest of their life.
4. Bone marrow transplants are very expensive and not an option for many people living with this disease around the world.
Both the doctors in Berlin and AIDS experts we’ve spoken with say this is a “proof of principle.” “It’s an interesting case for researchers,” according to Dr. Rudolf Tauber, from the Charite hospital in Berlin, where the patient was treated. The hope is that this one case could lead to future treatments. Dr. Gallo says, “If patients living with HIV and AIDS have access and can adhere to today’s retroviral therapy, many will live longer, healthier lives, perhaps full length lives.”
Editor’s Note: Medical news is a popular but sensitive subject rooted in science. We receive many comments on this blog each day; not all are posted. Our hope is that much will be learned from the sharing of useful information and personal experiences based on the medical and health topics of the blog. We encourage you to focus your comments on those medical and health topics and we appreciate your input. Thank you for your participation.
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