A cure for HIV?

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http://online.wsj.com/article/SB122602394113507555.html

Worth the read--text is below, diagrams are in the article.

The Wall Street Journal said:
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.

"I was very surprised," said the doctor, Gero Hütter.

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.

The development suggests a potential new therapeutic avenue and comes as the search for a cure has adopted new urgency. Many fear that current AIDS drugs aren't sustainable. Known as antiretrovirals, the medications prevent the virus from replicating but must be taken every day for life and are expensive for poor countries where the disease runs rampant. Last year, AIDS killed two million people; 2.7 million more contracted the virus, so treatment costs will keep ballooning.

While cautioning that the Berlin case could be a fluke, David Baltimore, who won a Nobel prize for his research on tumor viruses, deemed it "a very good sign" and a virtual "proof of principle" for gene-therapy approaches. Dr. Baltimore and his colleague, University of California at Los Angeles researcher Irvin Chen, have developed a gene therapy strategy against HIV that works in a similar way to the Berlin case. Drs. Baltimore and Chen have formed a private company to develop the therapy.

Back in 1996, when "cocktails" of antiretroviral drugs were proved effective, some researchers proposed that all cells harboring HIV might eventually die off, leading to eradication of HIV from the body -- in short, a cure. Those hopes foundered on the discovery that HIV, which integrates itself into a patient's own DNA, hides in so-called "sanctuary cells," where it lies dormant yet remains capable of reigniting an infection.

But that same year, researchers discovered that some gay men astonishingly remained uninfected despite engaging in very risky sex with as many as hundreds of partners. These men had inherited a mutation from both their parents that made them virtually immune to HIV.

The mutation prevents a molecule called CCR5 from appearing on the surface of cells. CCR5 acts as a kind of door for the virus. Since most HIV strains must bind to CCR5 to enter cells, the mutation bars the virus from entering. A new AIDS drug, Selzentry, made by Pfizer Inc., doesn't attack HIV itself but works by blocking CCR5.

About 1% of Europeans, and even more in northern Europe, inherit the CCR5 mutation from both parents. People of African, Asian and South American descent almost never carry it.

Dr. Hütter, 39, remembered this research when his American leukemia patient failed first-line chemotherapy in 2006. He was treating the patient at Berlin's Charité Medical University, the same institution where German physician Robert Koch performed some of his groundbreaking research on infectious diseases in the 19th century. Dr. Hütter scoured research on CCR5 and consulted with his superiors.

Finally, he recommended standard second-line treatment: a bone marrow transplant -- but from a donor who had inherited the CCR5 mutation from both parents. Bone marrow is where immune-system cells are generated, so transplanting mutant bone-marrow cells would render the patient immune to HIV into perpetuity, at least in theory.

There were a total of 80 compatible blood donors living in Germany. Luckily, on the 61st sample he tested, Dr. Hütter's colleague Daniel Nowak found one with the mutation from both parents.

To prepare for the transplant, Dr. Hütter first administered a standard regimen of powerful drugs and radiation to kill the patient's own bone marrow cells and many immune-system cells. This procedure, lethal to many cells that harbor HIV, may have helped the treatment succeed.

The transplant specialists ordered the patient to stop taking his AIDS drugs when they transfused the donor cells, because they feared the powerful drugs might undermine the cells' ability to survive in their new host. They planned to resume the drugs once HIV re-emerged in the blood.

But it never did. Nearly two years later, standard tests haven't detected virus in his blood, or in the brain and rectal tissues where it often hides.

The case was presented to scientists earlier this year at the Conference on Retroviruses and Opportunistic Infections. In September, the nonprofit Foundation for AIDS Research, or amFAR, convened a small scientific meeting on the case. Most researchers there believed some HIV still lurks in the patient but that it can't ignite a raging infection, most likely because its target cells are invulnerable mutants. The scientists agreed that the patient is "functionally cured."

Caveats are legion. If enough time passes, the extraordinarily protean HIV might evolve to overcome the mutant cells' invulnerability. Blocking CCR5 might have side effects: A study suggests that people with the mutation are more likely to die from West Nile virus. Most worrisome: The transplant treatment itself, given only to late-stage cancer patients, kills up to 30% of patients. While scientists are drawing up research protocols to try this approach on other leukemia and lymphoma patients, they know it will never be widely used to treat AIDS because of the mortality risk.

There is a potentially safer alternative: Re-engineering a patient's own cells through gene therapy. Due to some disastrous failures, gene therapy now "has a bad name," says Dr. Baltimore. In 1999, an 18-year-old patient died in a gene therapy trial. Even one of gene therapy's greatest successes -- curing children of the inherited "bubble boy" disease -- came at the high price of causing some patients to develop leukemia.

Gene therapy also faces daunting technical challenges. For example, the therapeutic genes are carried to cells by re-engineered viruses, and they must be made perfectly safe. Also, most gene therapy currently works by removing cells, genetically modifying them out of the body, then transfusing them back in -- a complicated procedure that would prove too expensive for the developing world. Dr. Baltimore and others are working on therapeutic viruses they could inject into a patient as easily as a flu vaccine. But, he says, "we're a long way from that."

Expecting that gene therapy will eventually play a major role in medicine, several research groups are testing different approaches for AIDS. At City of Hope cancer center in Duarte, Calif., John Rossi and colleagues actually use HIV itself, genetically engineered to be harmless, to deliver to patients' white blood cells three genes: one that inactivates CCR5 and two others that disable HIV. He has already completed the procedure on four patients and may perform it on another.

One big hurdle: doctors can't yet genetically modify all target cells. In theory, HIV would kill off the susceptible ones and, a victim of its own grim success, be left only with the genetically engineered cells that it can't infect. But so far that's just theory. All Dr. Rossi's patients remain on standard AIDS drugs, so it isn't yet known what would happen if they stopped taking them.

In 1989, Dr. Rossi had a case eerily similar to the one in Berlin. A 41-year-old patient with AIDS and lymphoma underwent radiation and drug therapy to ablate his bone marrow and received new cells from a donor. It is not known if those cells had the protective CCR5 mutation, because its relation to HIV hadn't been discovered yet. But after the transplant, HIV disappeared from the patient's blood. The patient died of his cancer 47 days after the procedure. Autopsy tests from eight organs and the tumor revealed no HIV.
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I think there was a similar case a few years back, too, where one guy became spontaneously HIV-free for reasons nobody could figure out. It was only a matter of time before some mutations started seriously resisting the disease.
 
Bono must read.

But in all seriousness, this is absolutely fantastic; it's an absolutely amazing development.
 
Brilliant, I'm so glad they are not getting flagged about this. Too often someone will find a radical new treatment and is banned from using it.

This treament has great potential and is being given the attention it needs.
 
shedinjask said:
Why would this be banned? It doesn't involve embryonic stem cells or illegal drugs.
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Sometimes it doesn't matter. People used to have to get perscriptions to get bananas.

But regardless, this is wonderful hopeful news!
 
HIV resistance has probably always been within the human genome. It's just our understanding of HIV has reached a point we would recognize that resistance.

This is awesome news and we might finally begin eliminating HIV and AIDS. Though, (if Polio is any indication) it could be a century before its completely eradicated.
 
Amazing.

But, about the genetic mutation, the CCR5-Δ32 strain is found in more than 'just' 1% of Europeans. More like 5% to 14% as the article says, with northern Europeans. But it's not resistant to HIV. It's only strongly protective, there's still a chance, however small, that someone with this gene could get infected – like said patient in the article, but would most likely recover in the duration of 2 years.

The CCR5-Δ32 was also linked to the Bubonic Plague of the 14th and 18th centuries as well as small pox epidemics throughout history, some people (again, like the very few percentage) were apparently resistant to the Black Death (ala Charles Darwin's natural selection theory). Though I'm sure scientists cannot verify claims and theories arising from some seven hundred years ago.

But I concur with Big Al, with the amount of people infected, to rid the world would take ages. And it's morbid to say, how many people will be affected along the way. The West Nile virus which makes people with the CCR5 gene highly susceptible to illness from said disease afflicts where HIV thrives — Africa.
 
Wow.

About damn time.

Hope this doesn't mean people start to carelessly be promiscuous.
 
What the hell? Nobody mentioned Autism.
 
First paragraph is all I needed to read.

Wonderful news, but there goes my ambition for finding the cure for AIDS :(
 
I think this is very good news!

This is a great first step for finding a cure, and hopefully, they will eventually.
 
Jigsaw said:
Wow.

About damn time.

Hope this doesn't mean people start to carelessly be promiscuous.
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I doubt it will have that effect on people. HIV/AIDs will continue to kill people. The science may be there, but it doesn't take into account the availability of a possible cure to those of lower incomes and no access to healthcare.

However, Magic Johnson will be elated.
 
I did a speech in speech class in college around '98 or so about this. At the time, and I apologize for forgetting the details, it wasn't so much the Plague scientists thought about, but the Greco-Roman ... uh ... promiscuity they thought helped bring about this mutation, which was later reinforced by the massive culling by the Plague.
 
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