Doctors Claim Stem Cell Cure

posted: 14/12/2010

Doctors who transplanted stem cells with HIV resistance to an HIV-infected man with leukaemia in 2007 say they believe he has been cured of HIV. The man is very unusual and treating most people in the same way won't work. But it does suggest new things to study.

A very small proportion of people (under 1 in 100) have natural resistance to HIV. This man was given matching bone marrow from a donor who has natural resistance to HIV infection. The donor doesn’t have the CCR5 co-receptor that HIV uses to lock onto the CD4 cell. People with this genetric mutation are almost completely protected against HIV infection.
 

The case was first reported at the 2008 Conference on Retroviruses and Opportunistic Infections in Boston, and Berlin doctors subsequently published a detailed case history in the New England Journal of Medicine in February 2009.
 

‘Reasonable to conclude’ HIV was cured
They have now published a follow-up report in the journal Blood, arguing that based on the results of extensive tests, “It is reasonable to conclude that cure of HIV infection has been achieved in this patient.”
 

The man's treatment story 
The 'Berlin patient' is an HIV-positive man who developed acute myeloid leukaemia, received successful treatment and subsequently experienced a relapse in 2007 that required a transplant of stem cells.
 

Doctors chose stem cells from someone who has a very unusual genetic profile: a mutation inherited from both parents that resulted in CD4 cells without the CCR5 receptor. This mutation, called CCR5 delta 32 homozygosity, is present in less than 1% of Caucasians in northern and western Europe, and is associated with a reduced risk of becoming infected with HIV.
 

All new infecting viruses need to use the CCR5 receptor on CD4 cells when infecting an immune system. Later on in HIV infections the CXCR4 receptor can also be used by HIV as a route into the CD4 cell.
 

Complex, costly, lengthy treatment
Before the stem cell transplant the man received chemotherapy treatment to destroy most of his immune cells and total body irradiation, and was given immunosuppressive drugs to prevent rejection of the transplanted stem cells.
 

Antiretroviral therapy was halted on the day of the transplant, and the man had a second stem cell transplant 13 days after the first one, because his leukaemia got worse.
 

The man continued to have immunosuppressive treatment to prevent rejection for 38 months, and at 5, 24 and 29 months post-transplant colon biopsies were taken to investigate possible graft-versus-host disease in the intestine. At each investigation additional samples were taken to check for signs of HIV infection in the abundant immune cells of the gut wall.
 

During the 38 month follow-up period the donor CD4 cells repopulated the mucosal immune system of the gut, to such an extent that the frequency of CD4 cells was almost twice as high as in HIV-negative healthy controls, and this phenomenon was also seen in a control group of ten HIV-negative individuals who received stem cell transfers.
 

The repopulation of CD4 cells was accompanied by the complete disappearance of host CD4 cells, and after two years the patient had the CD4 count of a healthy adult of the same age.
 

Longer lived HIV cells disappear
One of the challenges for any approach to curing HIV infection is long-lived immune system cells, which need to be cleared before a patient can be cured. In the case of the Berlin patient CCR5-bearing macrophages could not be detected after 38 months, suggesting that chemotherapy had destroyed these longer-lived cells, and that they had also been replaced by donor cells.
The German researchers and San Francisco-based immunologist Professor Jay Levy believe that the findings point to the importance of suppressing the production of CCR5-bearing cells, either through transplants, or gene therapy.
 

The man did not restart anti-HIV treatment after the transplant.
 

Ultimate undetectable
Nevertheless HIV remained undetectable by both viral load testing (RNA) and tests for viral DNA within cells, and HIV antibody levels declined to the point that the patient has no antibody reactivity to HIV core antibodies, and only very low levels of antibodies to the HIV envelope proteins.
 

Seventeen months after the transplant the patient developed a neurological condition, which required a brain biopsy and lumbar puncture to sample the cerebrospinal fluid for diagnostic purposes. HIV was also undetectable in the brain and the CSF.

An additional indication that HIV is not present lies in the fact that the patient’s CD4 cells are vulnerable to infection with virus that targets the CXCR4 receptor. If any virus with this preference was still present, the researchers argue, it would be able to swiftly infect the large population of memory CD4 cells that has emerged.
 

The Berlin patient speaks to the press
The `Berlin patient`, Timothy Ray Brown, a US citizen who lives in Berlin, was interviewed this week by German news magazine Stern.
 

His treatment for leukaemia was gruelling and lengthy. Brown suffered two relapses and underwent two stem cell transplants, as well as a serious neurological disorder that flared up when he seemed to be on the road to recovery.
 

The neurological problem led to temporary blindness and memory problems. Brown is still undergoing physiotherapy to help restore his coordination and gait, as well as speech therapy.
 

Friends have noticed a personality change too: he is much more blunt, possibly related to the neurological problems.
 

On being asked if it would have been better to live with HIV than to have beaten it this gruelling and complex way he says “Perhaps. Perhaps it would have been better, but I don’t ask those sorts of questions anymore.”
 

Stern also interviewed Dr Gero Hütter, who was in charge of Timothy Brown’s treatment. Dr Hütter told Stern that as a scientist he was “in the right place, at the right time” and that “for me it is important to have overthrown the dogma that HIV can never be cured. Something like this is the greatest thing one can achieve in medical research”.
 

Implications for HIV treatment future

If a cure has been achieved, it suggests one way to a cure for HIV infection is through genetically engineered stem cells.
 

The German researchers and San Francisco-based immunologist Professor Jay Levy believe that the findings point to the importance of suppressing the production of CCR5-bearing cells, either through transplants, or gene therapy.
 

Finding donors or transforming stem cells
Scientists were sufficiently intrigued by the Berlin patient that they met in Berlin in 2009 to discuss how they could coordinate efforts to identify CCR5-delta32 homozygous donors and expand the supply of stem cells from these donors, for example through sampling blood cells from the umbilical cord of babies born to mothers who are homozygous for CCR5-delta32, in order to eventually facilitate stem-cell therapy.
 

Gene therapy techniques which transform stem cells – and all their descendents – into cells resistant to HIV entry may be more practical than looking for rare matching donors.
Several US research groups announced in October 2009 that they had received funding to explore techniques for engineering and introducing CCR5-deficient stem cells.
If these approaches prove successful they will be expensive, so in the early stages it is likely that they would be reserved for people with no remaining treatment options or a cancer requiring bone marrow or stem cell transfer.
 

As Timothy Brown’s experience shows, curing HIV infection through ablative chemotherapy, immunosuppressive drugs and stem cell transfer is not a course of treatment for the faint-hearted. It has required courage, determination and a lot of support to become the first person to be pronounced `cured` of HIV infection.
 

Source with references
 

Prayer or Medicine? leaflet

posted: 16/11/2009

Mildmay, the international HIV charity based in London, have a leaflet that may be useful for some Christians with HIV concerned about treatment.

It deals with prayer, HIV treatments, and praying for healing. It quotes from the bible to show that using HIV treatments fits with Christian belief.

'It doesn't show lack of faith when we use medicines. Medicines are not different from everything else in creation: God gave them to us to use.'

"For everything that God created was good, and nothing is to be rejected if it is received with thanksgiving, because it is consecrated by the word of God and prayer."

1 Timothy 4 v4. New International Bible

Prayer or Medicines for HIV  leaflet

Mildmay

Harmed by Vitamin Claims

posted: 20/04/2009

The lives of tens of thousands of people, especially in South Africa, were needlessly shortened by unscientific claims to cure HIV simply with vitamins.
 

Dr Ben Goldacre wrote a best seller called Bad Science and now you can read, free, the chapter about falsely peddling vitamins as if they are a cure for HIV.

This chapter couldn't be included when the book first came out because the vitamin pill plugger, Matthias Rath, was still suing the author and the Guardian newspaper.

Maathias Rath lost, has already paid almost a quarter million pounds in compensation and legal costs, and still owes another £300,000.  He is a man who claimed vitamins cure cancer, cardio-vascular heart disease as well as HIV. Worse, he tells people the conventional treatments for these various conditions are harmful and must be replaced with vitamins. He makes a great deal of money from selling vitamins to the vulnerable and credulous.

In the case of HIV he got the president of S Africa and the health minister on his side. Thabo Mbeki gave Rath's ideas credence and support, and Mbeki and his minister bear a heavy responsibility for the deaths of thousands of people living with HIV.

This chapter - The Doctor Will Sue You Now - is free and shared on a Creative Commons Licence.

Bad Science 

Eliminate HIV from the World?

posted: 20/02/2009

Getting rid of HIV from the world is a dream that is becoming more reasonable to have. It might sound like fantasy: HIV infection has no cure and no vaccine, after all.

Yet there is a way to completely wipe it out - at least in theory. What's more, it would take only existing medical technology to do the job.

This is the start of a long article, in the latest issue of the New Scientist , that looks at the issues, problems and solutions and how we could do it.

What would it take to rid S Africa of HIV?

The most interesting section is where they discuss how it could be done.

Researchers looked at the case for elimination in South Africa, which has the highest number of HIV cases in the world. They modelled what would happen if everyone over 15 were given annual tests, with all those who tested positive offered free antiretroviral treatment immediately, regardless of their CD4 count. They plugged in actual figures from a free treatment programme in Malawi, to take account of people who refuse treatment, or who stop because of side effects, or who change treatments because of resistance.

10 years action would see HIV start to disappear

The team found that within 10 years, the scheme would slash new HIV infections from the 1 in 50 people at present to less than 1 in 1000. Within 50 years, as people with HIV died (mainly from other causes), prevalence in the general population would fall from about 10 per cent to less than 1 per cent.

That all sounds great, but the cost of the scheme would initially be about $3.5 billion a year. That might sound prohibitive, but the key comparison to make is with the cost of alternative plans.

....

Or in the UK?

It might be easier to attempt universal treatment in a developed country. For example, the UK could, if it chose, afford to put every one of its estimated 73,000 HIV-positive residents on antiretroviral therapy. On the other hand with HIV only affecting 0.1 per cent of the UK population, so the universal testing this would need would be hard to justify.

read the full report

Gene Therapy - a HIV Cure?

posted: 16/02/2009

A bone marrow transplant seems to have rid one man of HIV – and the doctors claim this is the closest thing yet to a cure for HIV. The New England Journal of Medicine has just published the details.
 

This could lead to new efforts to develop gene therapy for HIV, and this might end the need to take anti-HIV drugs for life. A single bone marrow transplant might be enough to eliminate the virus completely and permanently.
 

Not for most

But this method is not going to be available generally anytime soon, even to people in developed countries like the UK which have the money and advanced healthcare systems. Personalised bone marrow transplants will not provide a cure for the vast numbers of people living with HIV across the world.

A 42-year-old USA man living in Germany was infected with HIV for 10 years. He was treated with antiretroviral drugs in Berlin for four years, but he then developed leukaemia. Leukaemia is a type of cancer that affects the white blood cells.
 

Bone marrow transplant two years ago
He was given a bone marrow transplant two years ago (a standard treatment for serious cases of leukaemia), and since then he has not taken any more anti-HIV drugs; and both his HIV and leukaemia seem to have disappeared. He is believed to be the person who has lived longest since stopping his HIV treatment, without showing any further signs of HIV infection.
 

Full details are published for the first time today in The New England Journal of Medicine. An editorial says it "places further emphasis on gene therapies" for HIV, adding: "The case paves the way for innovative approaches that provide long-lasting viral control with limited toxicities for persons with HIV infection."
 

First find your bone marrow donor with a HIV genetic resistance gene
The man's treatment began with a search by doctors at Berlin's Charité Hospital for a bone marrow donor with a genetic resistance to HIV. Some people who have been exposed to the virus on many occasions remain uninfected – there is a well known report that some women sex-workers in Nairobi remained uninfected despite exposure to the virus by many sexual partners.
 

Some people carry a rare mutation of a gene (CCR5) that helps protect those with the gene from HIV. In Western populations between 1 in 100 and 3 in 100 have this protective gene mutation.
 

The doctors tested 61 potential donors before they found one with the CCR5 genetic mutation, who agreed to the operation. Finding bone marrow donors is always difficult. Giving bone marrow is uncomfortable and has some risks.
 

Scale of the problem
Gene therapy as a possible HIV treatment or potential cure is not going to come soon for most people. With over 5000 people diagnosed in NorthWest England, simply finding enough donors may not be realistic. In Berlin it took tests on 61 people to find one person who had the right gene and who also agreed to the procedure. It is possible that in time scientists will work out how to grow a few donors' bone marrow cells in the laboratory to treat many people. But for now it seems we would need to repeat the Berlin search for donors to individually match everyone diagnosed. Just for the NW of England, we might need to find over 300,000 potential bone marrow donors - equivalent to everyone living in any of the cities and boroughs of Greater Manchester and Merseyside.

The American recipient of the transplant, who runs a holiday rentals business in the German capital, has undergone regular checks in the two years since the treatment. The doctors have tested his bone marrow, blood and tissues and found no sign of HIV. "For as long as the viral load remains undetectable, this patient will not require antiretroviral therapy," they say in the journal.

Two for one treatment
Speaking last week, Dr Hutter said there had been several previous reports of patients being virus-free following treatment but none to compare with the latest case. "The difference is that in our patient we had a plan. It was not an accident," he added. "It is the longest time someone who has had antiretroviral therapy and stopped has lasted without the virus rebounding. Normally it rebounds within weeks. It is the closest we have come to a cure."
He doesn't explain his treatment plan, but it seems to have been to pick as a donor someone who had matching bone marrow to the Berlin man's, to restore his body's ability to make cancer-free white blood cells, who also had the rare gene that seems to protect people from HIV transmission - a two for one treatment plan.

Bone marrow transplants too risky for most
Dr Hutter said a bone marrow transplant would be too risky as a routine treatment for HIV and too difficult to find donors with the right genetic make-up. But a modification of the approach using gene therapy to give a person HIV-resistance could work, he said.
 

Even costly treatment that worked permanently to remove HIV would be worthwhile. The Independent, in its report, claimed the price of treatment with antiretrovirals in Europe is €70,000 to €80,000 Euros (£63,000 to £72,000) a year compared with a one-off cost of €20,000 to €30,000 Euros for a bone marrow transplant. However these drug costings seem grossly inflated, AIDS Treatment Update (May 2006) quoted typical UK costs as just £16,000 a year. A single bone marrow transplant would therefore cost slightly more than about one years' HIV drugs. If it worked consistently and was practical, investing in this would pay the NHS from the second year. Over a lifetime that would save much money as well as potentially restoring people to health, free of HIV. But there is no prospect of this in the foreseeable future. Bone marrow transplants are just too risky and complex - attempting to cure HIV by bone marrow transplants could kill or cause serious harm. The risks were only worth it in the Berlin man's case because he would have died soon otherwise from leukaemia.
 

Dr Hutter said: "When I started in medicine, HIV was completely untreatable. Now the situation has changed completely. Perhaps our case is a glimpse of hope for the future."
 

Cure, or is HIV still in hiding?
Professor Jay Levy, an Aids specialist at the University of California, and author of the US journal's editorial, said claims that the patient had been cured of HIV would be premature because of the virus's capacity to hide in other parts of the body including the brain, gut, liver and lymphatic system, from which it could always re-emerge.
 

"Nevertheless, the results... provide further encouragement for those examining approaches to treatment that reduce CCR5 expression in persons with HIV infection," he writes. In 2007, an estimated two million people died from Aids and 2.7 million were newly infected with HIV.
 

25 years of research: The HIV virus
When the discovery of HIV was announced in 1984, US politicians predicted that a cure for Aids would be found within five years, but it is still a distant prospect. Over the past 10 years, cocktails of effective antiretroviral drugs have been developed to help keep HIV at bay. Eliminating it has proved far more difficult because of the virus's unique nature. HIV integrates itself into an infected person's DNA and attacks the cells the immune system sends to attack it. Once infected, these T-cells take the virus deeper into the body.

Gene therapy is a new approach that harnesses the natural resistance to HIV shared by 3 per cent of people. Experts hope that by tweaking a person's DNA, they can achieve "long-lasting viral control".

Gene genie
Stem cells and gene therapy are likely to be a major source of treatments for many conditions over the coming years. It is very much in its infancy but scientists, doctors and the people who may benefit, are excited about some of the potential treatments now being tested and planned. And Bush's ban on stem cell research has already been lifted by President Obama, who has also announced major funding for stem cell research.

For now we wait to see what progress is made in developing treatments based on the CCR5 gene that provides protection. Any drugs that emerge may be no better than the others we already have. But they would be a new class of drugs and there is hope that such drugs might be far more effective.

source
stem cell technology prospects 
New England Journal of Medicine article