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Timothy Ray Brown has become the first known case of a person "cured" of the HIV virus. The cure came thanks to a chemotherapy treatment for a cancer he developed and a subsequent stem cell transplant.  (Source: Stern)

The success may eventually be able to replicated in others that suffer from HIV, but it will likely be very expensive.  (Source: South Park Studios/Comedy Central)

Timothy Brown shows no trace of HIV since his stem cell transplant in the summer of 2006.  (Source: www.peterrigaud.com)
Caustic cancer treatment regimen, combined with a clever genetic trick kicked the pesky HIV virus out for good

Timothy Ray Brown might seem very unfortunate if you knew some aspects of his medical story.  A U.S. citizen living abroad in Berlin, Mr. Brown was diagnosed with acute myeloid leukemia.  

As the disease spread through his bone marrow, he was forced to undergo grueling chemotherapy and then a stem cell transplant.  Then the disease flared up yet again, forcing yet another stem cell transplant. 

Finally recovering, he then suffered an unexpected neurological side effect, which left him forgetful and temporarily blind.  He had to undergo therapy just to be able to try to walk and talk normally.

But the treatment did something incredible, something that has never before been documented in the modern medical community -- it cured Mr. Brown of the human immunodeficiency virus -- better known as HIV.

Deadly, but Effective

Approximately 1 percent of Caucasians in northern and western Europe have a special mutation that virtually prevents them from being infected with the HIV virus.  The mutation, dubbed CCR5 delta 32 homozygosity, causes individuals to lack the CCR5 receptor, which the HIV lentivirus uses to accomplish its infection process.

Physicians treating Mr. Brown's cancer purposefully selected a donor who happened to have this beneficial mutation. 

Hopes of a cure seemed faint, though.  After all, if the HIV infection in Mr. Brown's former CD4 (T-cell) population had advanced enough, it would have developed the ability to infect using the CXCR4 receptor, rendering the protective mutation useless.  And even if the virus had not armed itself with this new ability, no one had ever been cured of the disease.

While Mr. Brown may have been unfortunate by and large medically, he apparently lucked out when it came to his HIV infection.  

Taken abruptly off antiretroviral drugs after the transplant, he showed no signs of HIV infection.  For the next 38 months he underwent immunosuppressive treatment to protect the graft as it repopulated his intestinal mucosa.

Tissue samples taken during this time period showed spiking levels of the donor T-cells and no trace of infection.  Weaning off immunosuppressants, the man's T-cell levels dropped to that of a healthy adult male.

Medical researchers concluded that it was unlikely that the man still had HIV -- after all if he had the disease, it would have likely evolved the CXCR4 infection ability and infected his immunotransplant.

Further evidence the disease was gone was shown by dropping levels of his body's HIV antibodies.  And viral load testing (RNA) and tests for viral DNA within cells -- two tests that typically reveal the presence of HIV -- came back negative.

Can Doctors Replicate This Unusual Success?

Mr. Brown's ordeal was chronicled in the German magazine Stern.

The results have also been published in an article in the peer-reviewed journal Blood and a study [PDF] in The New England Journal of Medicine.

As the magazine notes, past attempts to graft "immune" T-cells failed, due to the long lifespans of the victim's infected T-cells.  Those long lifespans bought the virus enough time to mutate and overcome the graft's immunity.  But in Mr. Brown's case, the chemotherapy killed enough of the infected cells that the mutation was not able to occur.

While the treatment regiment is extremely dangerous, chemotherapy -- long aimed at curing cancer -- may soon be used to cure HIV.

The key remaining obstacle is to develop ways to create CCR5 deficient T-cells. 

Mr. Brown was fortunate in that a donor was found who happened to have this mutation.  Most won't be that lucky.  But researchers are hoping to create stem cells from the patient's various cell lines, differentiate them into T-cells, and finally using gene therapy to knock out the CCR5 receptor DNA.

The resulting treatment may not be correct for everybody.  HIV is largely repressible with today's advanced drug regimens.  Some may decline to risk their lives to be pronounced "cured".

For those who may someday opt for this route, the resulting treatment will likely be very expensive.  Thus South Park's irreverent recent episode "Tonsil Trouble", which depicted NBA-great Magic Johnson being "cured" of HIV via a money transfusion may prove somewhat prophetic.



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CCR5
By jimhsu on 12/14/2010 10:07:03 PM , Rating: 3
It's long known that individuals with the CCR5-?32 mutation are long-term nonprogressors (i.e. they lack the proper receptor required for HIV (the R5 strain at least) to enter the cell). HOWEVER, this is not consistent with the assertion that individuals with the mutation have unaffected CXCR4 that can allow HIV in: in fact, there is a direct interaction between CCR5 and CXCR4 with CCR5?32 protein in CCR5-?32 mutations, suggesting that there is a direct interaction between the mutant protein and functional CCR5 and CXCR4 receptors, which results in resistance to a wide range of HIV viruses including X4 which uses the CXCR4 receptor [source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC369216... ].

In short, the article is not exactly correct when stating that defective CCR5 receptors cause HIV viruses to adapt and use CXCR4 instead.




RE: CCR5
By JasonMick (blog) on 12/15/2010 8:25:01 AM , Rating: 3
er... I specifically mention this...

quote:
Hopes of a cure seemed faint, though. After all, if the HIV infection in Mr. Brown's former CD4 (T-cell) population had advanced enough, it would have developed the ability to infect using the CXCR4 receptor, rendering the protective mutation useless. And even if the virus had not armed itself with this new ability, no one had ever been cured of the disease.


...and

quote:
Medical researchers concluded that it was unlikely that the man still had HIV -- after all if he had the disease, it would have likely evolved the CXCR4 infection ability and infected his immunotransplant.


My understanding is that the CCR5 variant of the virus is the primary one transmitted by infection. Thus newly infected persons could likely undergo this treatment, before their infection mutated, as I suggested...


RE: CCR5
By geddarkstorm on 12/15/2010 8:42:58 AM , Rating: 3
HIV is sadly pretty complex, with numerous subtypes. Only subtype B is obligate to use the CCR5 receptor from the start, so it's diminished in infectivity by at least 70% when this d32 mutation is heterozygous, and basically completely stopped when homozygous. Other subtypes use the CD4, and the CCR2 and CCR5 receptors in the beginning, which allows them to be somewhat resistant to this mutation.


RE: CCR5
By nstott on 12/15/2010 12:00:10 PM , Rating: 2
I watched a documentary many years ago where they traced a genetic mutation in modern people immune to HIV, showing them to be the descendants of Europeans who survived the bubonic plague during the Dark Ages.

As for the absence of HIV in this case, is it possible that the treatment reset the infection such that it is lying dormant like it typically does during the initial stages? Even so, assuming the immune system was not wiped out during the aggressive chemotherapy treatment, then HIV should not be able to build up sufficiently to push past equilibrium into full-blown AIDS when the immune system is put under stress from other non-HIV sources.


RE: CCR5
By Samus on 12/15/2010 8:28:31 PM , Rating: 2
CCR5 is the only strain spread sexually or through blood. CXCR4 is a mutation that occures once infected and does not leave the body. CCR5 and CXCR4 co-exist in those with CCR5 infections, and work together resulting in AIDS. If you lack CCR5 receptors, you can not be infected with HIV.

However, there are over 80 mutations of HIV and we are only talking about one.


RE: CCR5
By geddarkstorm on 12/15/2010 8:30:30 AM , Rating: 2
Yeah, there are actually two major strains of HIV, Type I and Type II, which behave differently in how they infect and respond to treatments. But that's a little known fact strangely enough.

Still, to actually cure this is a major breakthrough. And thanks for posting that important info for everyone.


RE: CCR5
By jimhsu on 12/15/2010 7:46:04 PM , Rating: 2
The weird thing is that HIV-2 is much less pathogenic than HIV-1; it stands to reason that if HIV ever becomes a significant selecting force (i.e. in sub-saharan Africa), HIV-2 could possibly outcompete HIV-1 by simply not causing the host to die -- a "successful (in an evolutionary sense)" virus is essentially one that causes mild symptoms, but has very high infectivity -- therefore, the largest possible number of people get and transmit it. Thus, if HIV-2 competes with HIV-1, we could possibly see more, but less severe HIV cases in the near future ("near" being hundreds to a few thousand years).


ummmm....
By Iketh on 12/14/2010 10:12:16 PM , Rating: 5
clearly the HIV thought this guy had too many problems and left on its own




RE: ummmm....
By AnnihilatorX on 12/15/2010 5:07:51 AM , Rating: 3
If viruses started to think and act despite being non-living biotoxins we too have a problem :)


RE: ummmm....
By Flahrydog on 12/15/2010 9:18:45 AM , Rating: 2
we may already have a problem :)

Virus-Infecting Virus Fuels Definition of Life Debate
http://news.nationalgeographic.com/news/2008/08/08...


Zombies
By asd1 on 12/15/2010 1:37:54 AM , Rating: 2
Wasn't T-cell something out of RESIDENT EVIL :D?




RE: Zombies
By AnnihilatorX on 12/15/2010 5:05:41 AM , Rating: 2
It's T-virus in the Resident Evil series.
T-cells are one type of cells of our immune system, along with B-cells and others.


RE: Zombies
By asd1 on 12/15/2010 5:16:58 AM , Rating: 2
mutated version


what about this other way, did it work?
By Silver2k7 on 12/15/2010 1:54:58 AM , Rating: 2
There was some doctor that did run the pasients blood through somekind of eletrical device, that supposedly killed off all of the virus that went through the machine. If this story is true all that was remaining was very low levels of virus in blood wich didnt go through the machine, from bloodveins in the ears etc.

IIRC this was done by a Doctor Bob Beck, if this device existed it would be better to use, way less dangerous for the patient than chemotherapy anyway. After killing off most of the virus I suppose this kind blood donation from an immune donor discussed in the article, could do its thing.




By mooty on 12/15/2010 9:04:26 AM , Rating: 2
Killing a virus in that sort of manner would involve killing all the cells that contain the virus. Even if a device like that would only kill the T-cells, a significant number of those does not circulate in the blood stream.

Rest assured, that if that kind of machine did exist, and it did work, it would be used.


Old news?
By UNCjigga on 12/14/2010 7:23:06 PM , Rating: 3
I thought this story came out in 2008? I guess it took 2 more years before it was *OFFICIAL* *CONFIRMED*??




It all makes sense now
By Lord 666 on 12/14/10, Rating: -1
RE: It all makes sense now
By Doc13 on 12/14/2010 7:26:20 PM , Rating: 5
Actually he banned the use of federal funds in embryonic stem cell research. States & corporations were free to research whatever they wanted as long as federal funds were not involved.

California prop 71 created a $3 billion fund to research potential uses of embryonic stem cells. I moved out of state just after this so I am not sure what sort of progress they have made.

As this procedure uses adult stem cells none of the restrictions applied.


RE: It all makes sense now
By torpor on 12/14/2010 9:00:59 PM , Rating: 5
Actually, Bush didn't even go that far.

He only stopped use of federal funds for new embryonic lines. The 21 lines which were already in existence were allowed ("where the life and death decision had already been made"), making Bush the first President to allow any funding of embryonic stem cell research.

Funding for any experimentation where embryos had been destroyed/harmed was completely banned under Clinton. Bush's action actually represented a significant loosening of the federal purse. But we don't talk about that in nice company.

I would add that the massive advances in our ability to create stem cells in non-destructive ways comes in large part from the public position Bush took on the issue. It is a complete vindication of his principled stand that we don't even need them anymore. Please notice that the advance in this article required the death of no humans whatsoever - the stem cells came from a living adult.


RE: It all makes sense now
By Lord 666 on 12/14/10, Rating: -1
RE: It all makes sense now
By twhittet on 12/15/2010 12:34:24 PM , Rating: 2
Apparently you need some practice at it.


RE: It all makes sense now
By guffwd13 on 12/15/2010 1:25:13 PM , Rating: 2
i agree. you seem to fail to realize that everything you wrote is a viewpoint shared by a large population of the US. wherever you're from, you seem to lack exposure to the other half of the argument if you think what you wrote was far fetched.

(off topic) but then again, I had the same issue with one of my first posts to DT:

quote:
Dear Canadian, I am American. We own the fscking world. We eat steak because its good for you. We start wars because we can. We smoke because its a God-given right, and we carry rifles in the backs of our pickups in case any illegal-ass alien canadians cross the border into the Promised Land. We even invented doctors and you're mouthin' off that our bullet-proof capitalistic health care system can even be equated to? I knew the rest of the world was still living in the stone age, but man, sometimes I just don't get.


i was really surprised when people thought i was serious.


RE: It all makes sense now
By Mudhen6 on 12/14/2010 9:00:25 PM , Rating: 4
To add to this, stem cell therapy didn't cure HIV. Nuking the patient's immune system with chemotherapy first before the virus developed the ability to use the CXCR5 co-receptor is arguably the key to the "cure" in this case.

If the chemo didn't take place, the HIV would reside within the patient's T-cells in their gut until they develop the ability to use CXCR5 and the ability to resist HAART therapy (atm machine).


RE: It all makes sense now
By Mudhen6 on 12/14/2010 9:06:05 PM , Rating: 2
CXCR4*

Wow, that was facepalm worthy.


RE: It all makes sense now
By jimhsu on 12/14/2010 10:16:20 PM , Rating: 2
Since CCR5-D32 is essentially a recessive allele, I would expect that the reason for "nuking" the patient first is to delete bone marrow stem cell populations, to a) reduce deleterious rejection reactions, and as a side effect b) get rid of normal CCR5 receptor populations so that only cells with defective CCR5s are made. They specifically transplanted homozygous D32/D32 stem cells for this reason. (skimmed the abstract of the paper linked)

Death of patient T-cell populations only decreases the population of normal CCR5 receptors so that the cells with defective ones can replace the original population.


RE: It all makes sense now
By Lord 666 on 12/14/2010 10:37:14 PM , Rating: 2
The true test is if he can be made HIV positive again.


RE: It all makes sense now
By Lord 666 on 12/14/10, Rating: 0
RE: It all makes sense now
By sleepeeg3 on 12/14/2010 10:49:22 PM , Rating: 3
The "pubonic" plague? Does that involve deadly itching? I think I have that...


RE: It all makes sense now
By Lord 666 on 12/15/2010 11:23:02 AM , Rating: 2
Sorry for the typo - http://en.wikipedia.org/wiki/Bubonic_plague

However, not sure why this post of mine was rated down. This German chap had leukemia as well and was treated with bone marrow containing the mutant gene.

Deeply and openly search the history of HIV and leukemia and you can see I am hinting at something.


RE: It all makes sense now
By amanojaku on 12/14/2010 7:27:21 PM , Rating: 2
WHAT? I don't love Bush, and think all politicians are scum, in general, but I think you're cracked. I'm pretty sure he banned it based on ethical grounds: he didn't want ANY stem cell source that wasn't adult, to rule out abortions as a potential source.

As to the business end, you think this guy's treatments were cheap? There is money to be made in all types of medicines.


RE: It all makes sense now
By hivsingle on 12/14/10, Rating: -1
RE: It all makes sense now
By ekv on 12/15/2010 4:14:30 AM , Rating: 1
If you happen to fall into the following category

http://www.buzzle.com/editorials/1-26-2003-34364.a...

http://en.wikipedia.org/wiki/Bugchasing_and_giftgi...

even though you are likely a decent person, albeit very confused, your behaviour is irresponsible. "Please" do not ask/force me to pay for your chemo....


RE: It all makes sense now
By robinthakur on 12/15/2010 7:02:41 AM , Rating: 2
Completely agree, although I would like to point out that this is not limited to gay men in its scope. In the UK the majority of new HIV infections are amongst heterosexual people nowadays, but the risk exists for anybody practicing unsafe sex. Knowingly giving HIV to somebody is classed as attempted murder in large parts of the world's justics systems.

This is a tiny infinitely small clique (gay or straight) and I have never encountered it personally, I have merely read about it in the media, and usually in the context that it originated in America. Whilst it's a terrifying thing for many reasons, the pyschology and group behaviour behind it is intensely fascinating.


RE: It all makes sense now
By wordsworm on 12/14/10, Rating: -1
It ALL makes sense now...
By ma2ree on 12/15/10, Rating: -1
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