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Author Topic: Technology Review Jul 2010 - Can AIDS Be Cured?  (Read 6107 times)

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Offline Boze

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Technology Review Jul 2010 - Can AIDS Be Cured?
« on: June 22, 2010, 01:23:59 AM »
http://www.technologyreview.com/biomedicine/25563/

July/August 2010

Can AIDS Be Cured?


By Jon Cohen

In an aging research building at the University of Southern California, a $14.5 million biomedical experiment is under way that until a few years ago would have made many AIDS researchers snicker at its ambition. Mice are the main research subjects (for now), and some 300 of them live in a room the size of a large walk-in closet. Signs plastered to the room's outer door include blaze-orange international biohazard symbols and a blunter warning that says, "This Room Contains: HIV-1 Infected Animals." Yet the hazard is accompanied by an astonishing hope. In some of the infected mice, the virus appears to have declined to such low levels that the animals need no further treatment.

This is a feat that medications have not accomplished in a single human, although daily doses of powerful anti-HIV drugs known as antiretrovirals can now control the virus and stave off AIDS for decades. Every person who stops taking the drugs sees levels of HIV skyrocket within weeks, and immune destruction follows inexorably. The lack of a cure--a way to eliminate HIV from an infected person or render it harmless--remains an intractable and perplexing problem.

"This doesn't look like a multimillion-dollar operation at all, does it?" jokes Paula Cannon, a lead researcher on the project, as she enters the ill-smelling room, which has shelves lined with mice living together in plastic cages that resemble large shoeboxes. As she leads a tour of the cramped space, Cannon wears a face mask, a hairnet, a gown over her clothes, latex gloves, and cloth shoe coverings over her stylish heeled boots. She takes these precautions not to protect herself but to ensure that she won't transmit a dangerous infection to this colony of mice--which is worth somewhere around $100,000.

The experiment costs so much in part because Cannon and her team had to purchase mice bred to have no immune systems of their own; the AIDS virus normally
cannot copy itself in mouse cells, making ordinary mice worthless as disease models. Human immune-system stem cells are transplanted into pups bred from these mice when they are two days old, and over the next few months, those cells mature and diversify into a working immune system. Then the mice are infected with HIV, which attacks the immune cells. But before transplanting the original human cells, the researchers introduce an enzyme that interferes with the gene for a protein the virus needs to stage the attack. This modification makes a small percentage of the mature immune cells highly resistant to HIV, and because the virus kills the cells it can infect, the modified cells are the only ones that survive over time. Thus, the HIV soon runs out of targets. If this strategy works, the virus will quickly become harmless and the mice will effectively be cured.

Results from the mouse experiments are encouraging so far, and Cannon hopes they will lay the groundwork to begin human studies soon. "I want to cure AIDS by my 50th birthday," she says; she is now 47. And though she says she is only half serious, her ambition is clear: "I'm looking for a home run."

In the HIV research community, "cure" has long been considered the dirtiest of four-letter
words: over the years, various promising approaches have failed, leaving overhyped headlines, crushed hopes, and dispirited scientists in their wake. HIV simply excels at dodging attack, both by mutating and by lying low in a latent, or inactive, form in which it still remains viable. In such a dormant state the virus can survive for decades, completely untouched by the drugs now on the market. Any attempt to flush this latent virus out of hiding risks doing more harm than good: the treatment itself could be toxic, or it could unwittingly strengthen the infection.

But over the past few years, leading AIDS researchers have begun speaking again of the prospects of a cure. For many, such as Cannon, the goal is a "functional" cure that would allow patients to stop taking antiretroviral drugs without risk of harm from the small amount of HIV left in their bodies. Other, more ambitious investigators want to eradicate the virus totally--what they call a "sterilizing" cure; they are buoyed by an improved understanding of what creates and maintains the reservoirs of latent virus. Either way, the goal is to get HIV-infected people off a lifetime course of drugs.

Douglas Richman, a virologist at the University of California, San Diego, who has cared

for HIV-infected people for years, now has patients who have kept the virus completely in check with drugs for up to 17 years. "They're going to outlive me," says Richman, who is 67 years old. "They're not going to die of AIDS. That's wonderful, but do we have to have tens of millions of people on lifetime treatment?"

Such treatment has rising costs, both monetary and medical. In wealthy countries, annual drug expenses run into the thousands of dollars per HIV-infected person. Much cheaper generic versions of the drugs have been given to four million patients in poor countries, but the rich governments footing most of that bill are now cash-strapped and worried about sustaining the charity. And an estimated five and a half million more people urgently need treatment but have no access.

What's more, living with HIV for decades can be medically problematic. Even low levels of the virus can leave patients more susceptible to diseases of aging: heart attacks, malignancies, disorders of the central nervous system. Some of these ailments are side effects of the drugs themselves. People on treatment can have damaging surges of virus, too, when they occasionally stop their drugs or develop resistance to the compounds. "There are five million new infections a year, and three million deaths," says Richman. "So we're just going to have more and more people living with HIV."

Cannon's gene therapy experiment is one of a dozen similar projects in the works that hold the promise of ending patients' dependence on antiretroviral drugs. It's an ambitious dream. But it's no longer as quixotic as it once seemed, and she is approaching her experiment with realistic expectations and the conviction that other researchers' progress will work in concert with her own. "I think in steps," says Cannon. "Will the first person on our treatment be the home run? No. But we may see some benefit. And if you have an imperfect success, it's still a success." Especially when the goal is so grand that it could
profoundly alter millions of individual lives--and the course of the AIDS epidemic itself.

TABOO
Talk of a cure began shortly after the epidemic surfaced in 1981, but for 15 years it was just talk. Even the best HIV treatments did little to hamper the virus. Then, in 1996, researchers reported a remarkable breakthrough using new combinations of antiretrovirals: they could suppress the amount of virus in the blood below the levels that standard tests could detect, allowing immune systems to rebound and people near death to resume normal, healthy lives. Small amounts of the virus could still be detected in these patients by running more sensitive blood tests and analyzing hideaways like lymph nodes or the gut, but the dramatic success of the treatment led prominent AIDS researchers to believe for the first time that the idea of curing HIV was truly realistic.

David Ho, head of the Aaron Diamond AIDS Research Center in New York City, became a media sensation after he spoke at the international AIDS conference held in Vancouver, British Columbia, in July 1996. Ho had done
mathematical calculations showing that if drugs could suppress the virus to this degree, it would take, at most, around three years to eradicate HIV from a patient. His clinical team had an ideal population in which to test the theory: eight patients who had started the powerful drug cocktails shortly after becoming infected, which presumably prevented the virus from ever multiplying to astronomical levels. If all went well for a few more years, these people would stop taking their treatments and, the investigators hoped, never see the virus return.

As much as the headlines celebrated Ho--Time magazine named him Man of the Year in 1996--many colleagues were deeply skeptical. "In every field--pancreatic cancer or brain cancer or Alzheimer's--it's okay to say 'I'm working on a cure,'  " Ho says. "For HIV/AIDS, it was a taboo."

In May 1997, when Ho and his collaborators published their calculations in Nature, they emphasized that surprises might be lurking around the corner. "Although significant progress has been made in the past year in the treatment of HIV-1 infection, it would be wrong to believe that we are close to a cure for AIDS," they wrote.

"However, the recent advances in treatment and pathogenesis do warrant a close examination of the feasibility of eradicating HIV-1 from an infected person."
As it turned out, the surprise was lurking in the same issue of Nature, which included a report by Robert Siliciano's group at Johns Hopkins University School of Medicine in Baltimore that used a sophisticated assay to identify a reservoir of cells in which HIV infection was latent. Ho's calculations had not included these cells. Siliciano's measurements, however, would show not only that they were detectable in all HIV-infected people, regardless of the virus levels found in their blood, but that they were, by nature, extremely long-lived.

HIV selectively infects and destroys CD4s, a type of white blood cell called a T cell that coördinates immune attacks. The cells are so named because of the receptor, CD4, on their surfaces--one of two that HIV needs to start the infection process. Once the virus successfully docks on the CD4 cells, it unloads its RNA, which is transformed into viral DNA that weaves itself into the human chromosomes in the cell's nucleus. In most cases, the virus makes millions of progeny within a day; they burst out of the infected cell, either killing it directly or marking it for destruction by the immune system. But in some CD4 cells, the viral DNA integrated into the chromosomes lies dormant.

The circumstances that cause this to happen are somewhat random, says Eric Verdin, a researcher into the molecular biology of HIV latency who is based at the Gladstone Institute of Immunology and Virology at the University of California, San Francisco. Perhaps the HIV has infected a CD4 cell that is in a "resting" phase of its life cycle, or perhaps the viral DNA has infiltrated an odd part of a chromosome that prevents its genes from operating. "Latency is not a biological property of the virus," says Verdin. "HIV couldn't care less whether it becomes latent." When it does, however, the virus can effectively hide from
the immune system--and from antiretroviral drugs. The trouble begins when a resting CD4 cell becomes active after infection or other events somehow activate the virus. Then this latent HIV can launch a new round of viral replication.

In 1999, Siliciano showed that a person on antiretrovirals who has otherwise undetectable viral levels in the blood will still harbor around a million latently infected cells. He calculates that it would take more than 50 years of fully suppressive treatment to clear these reservoirs as the latently infected cells slowly died or the dormant HIV came out of hiding on its own. Indeed, when the patients that Ho's team was studying stopped taking their drugs after their infection had been suppressed for an average of 3.2 years, the virus quickly came back in all cases. Every other research group that tried this experiment had the same dispiriting results. By the turn of the millennium, it was clear that curing an HIV infection would require a new line of attack. Siliciano says, "It's now well accepted that this latent reservoir is going to be a barrier to eradication, and that it's extremely stable and it's never going to decay significantly without specific interventions."

Some scientists argued that HIV returned
because the drugs were simply not keeping all of the active virus from copying itself, even in people whose infection was undetectable on standard tests--which can detect the virus if there are only 50 copies in a milliliter of blood. They speculated that a low level of viral replication was sufficient to refill the pool of latently infected cells faster than they could be eliminated. So in several studies these people received extra antiretrovirals, a strategy called intensification. "Absolutely nothing happens," Siliciano says. "The level of virus doesn't budge at all."

Ho and others still believe that the current drugs may be able to fully suppress the virus. But the question has largely become academic, because no intensification effort has yet reduced latent infection in any significant way. Siliciano thinks people should stop expecting more from anti-HIV drugs. He says, "We've reached the theoretical limit."

MAGIC FINGERS
In the spring of 2006, Gero Hütter, an oncologist then working at the Charité Medical University in Berlin, saw a 40-year-old patient who had been on anti-HIV drugs for four years. The virus was undetectable in his blood, and his immune system was reasonably intact. But he had another,

unrelated problem: acute myeloid leukemia, a blood cancer that threatened his life. Hütter, who now works at the Heidelberg Institute for Transfusion Medicine and Immunology in Mannheim, put the man on repeated rounds of chemotherapy, but after seven months, the leukemia returned. The next option was a stem-cell transplant, which would be preceded by a course of drugs to kill his immune cells--a dangerous procedure called ablation. Although the transplant would come from an immunologically matched donor, some of his own immune cells would probably remain viable, so rejection remained a risk; the physicians would try to reduce it with still other dangerous drugs. One-third of those in the man's condition don't survive the procedure.

Although Hütter was not an HIV specialist, he knew about a mutation found in about 1 percent of people of European descent that makes their CD4 cells highly resistant to HIV. The mutation cripples a second receptor, CCR5, that the virus uses in concert with CD4 to establish an infection. If doctors could find a stem-cell donor who had this CCR5 mutation, Hütter told his patient, the transplant could theoretically enable his body to control any remaining HIV without antiretroviral drugs. "I told him we don't know what will happen, but there might be a chance we'll get rid of HIV," Hütter recalls. "He said, 'I don't care about this--I have no problem with antiretrovirals.' He was scared from his leukemia."

The patient changed his mind, and in February 2007, Hütter and his colleagues performed the transplant with stems cells that had the mutant CCR5. The man then stopped his antiretrovirals. His HIV levels remained undetectable, and the doctors stopped finding evidence of

$$COL$$
latently infected cells after about two months. A year later, the leukemia recurred; he received ablation with whole-body irradiation and then a second stem-cell transplant. As of today, he remains healthy, and his HIV levels are undetectable by Hütter and his team. Even samples sent to Siliciano's lab and other U.S. facilities that have the most sensitive assays have come up empty. Says Siliciano: "I think he's cured."

The results are tantalizing, but what they mean for most infected people is uncertain. As Siliciano cautions, it could be that destroying his immune cells would have cured the man no matter what replaced them. And although a CCR5 mutation stymies the most common HIV strains, some can use different co-receptors; if they are lurking inside the Berlin patient in latent form, they could one day resurface. Even Hütter says he would like to see a few more years pass with no virus before declaring the patient HIV-free. But there's widespread agreement that he has, at least, been functionally cured. "The Berlin patient
stunned the whole field, because people didn't expect it would work that well," says Verdin. "It's obviously not replicable to the whole HIV population--the cost, the risk, is just incredible. But what it really shows is you can have a functional cure with no other side effects."

Paula Cannon is betting that the immune cells with the CCR5 mutation did cure the Berlin patient. If she could use gene therapy to knock out CCR5 in a person's own stem cells, Cannon would sidestep the thorny problems involved in finding matching donors with the mutation and then combating immune rejection after a transplant. Indeed, her interest in this strategy predates the Berlin transplant, but she says its apparent success has provided further encouragement. "I always thought CCR5 was an obvious target, and the whole thing with the Berlin patient has everyone on the same page," she says. Cannon believes that this case was part of the reason why, last October, the California Institute for Regenerative Medicine awarded her team's proposal more than $14.5 million. "I love the

Berlin patient," she says. "I'd like to take him out to dinner."

In trying to cripple CCR5, Cannon is building on the efforts of many others. Sangamo Biosciences, a biotech company in Richmond, CA, designed an enzyme called a zinc finger nuclease that can specifically target the CCR5 gene and disrupt its function. Working with Sangamo, Carl June, a gene therapy investigator at the University of Pennsylvania, now has a human study under way in which CD4 cells are pulled from HIV-infected people, infected with an adenovirus that carries the zinc finger nuclease, and then reinfused into the patients. But Cannon's work would take things one step further. By targeting the CCR5 gene in the stem cells that give rise to the CD4s, Cannon, who is also working with Sangamo, thinks she ultimately has a better chance of achieving an effective and durable cure.

To test the idea, Cannon's lab transplants human stem cells into one group of mice that serve as controls. A second group of mice receive human stem cells that have been modified with the zinc finger nuclease. The researchers then infect the mice with HIV. Experiments on numerous groups of mice show that the virus initially does equally well in all the animals, but after a few weeks, viral levels nosedive in the treated mice.

The zinc finger nucleases successfully mangle the CCR5 gene in only about 5 percent of the mouse immune cells. But HIV selectively kills the cells whose CCR5 receptors are intact. Thus, Cannon contends, the proportion of cells with a broken CCR5 receptor will increase over a few weeks, until the virus can no longer spread: even if a latently infected cell starts churning out HIV, it has nowhere to go. So the treated mice remain infected, but at such low levels that they suffer no ill effects. " 'Cure' doesn't mean you have to eliminate the virus," says Cannon. "You just have to eliminate the consequences of viruses. It's a Herculean task to remove every cell in the body that has HIV in it."

==========
Aug08 - Seroconversion
Mar10 - Diagnosis; cd4 690 - VL 19,000
Apr10 - cd4 600
May10 - VL 4,500
Jun10 - started Atripla ; VL 113
Jul 10 - UD vl, CD4 590
Aug 10 - UD, CD4 810, 52%
Nov 10 - UD, CD4 980

Offline Boze

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #1 on: June 22, 2010, 01:25:15 AM »
HERCULEAN TASK
Some AIDS researchers still find that Herculean task worth

$$COL$$
pursuing. To them, the functional cures that Cannon and others are pushing for have merit but do not ultimately solve the problem. After all, an HIV strain that does not need CCR5 may be hiding in the body. Or maybe a latent virus will pop out and somehow mutate in such a way that it does not need CCR5 either. History, of course, is not on the side of those who want to wipe out the virus completely. "It's incredibly heartening to see more people looking at eradication more carefully," says David Margolis, a clinician at the University of North Carolina in Chapel Hill, who has done some of the first drug studies in humans that seek to purge the reservoir of latent HIV. "But it's going to take a lot of hard work by a lot of people for a long time to really make progress. Who knows where the next real advance will come from?"

If current antiretrovirals do indeed completely stop HIV from copying itself, the remaining steps toward eradication will be to identify the location of the latent reservoirs and to flush the virus out of them and into the bloodstream, so the drugs can do their work. Researchers know that one place the latent virus hides is in resting CD4 cells, but Siliciano has

$$COL$$
published molecular evidence that this cannot be the only reservoir. One recent report from scientists at the University of Michigan suggests that inactive HIV can lurk in bone-marrow stem cells, and the virus could also be in the brain, gut, and lymph nodes. Checking for HIV in any of these tissues is much more difficult than analyzing a blood sample, so it won't be easy to determine how effective a therapy has been at wiping it out.

Regardless of where latent HIV is, the virus must be awakened before drugs can target it. In the late 1990s, David Ho and a few other research groups made a crude attempt to do this. They explored the idea of prodding resting CD4 cells to "activate" and start making copies of themselves; in the process, those latent cells that harbored HIV would transcribe their viral DNA and then die. Ho's group treated one patient with a monoclonal antibody that triggers activation. "He got pretty sick, and we just stopped it," Ho remembers. "It was too scary." A similar attempt almost killed another patient. "For the past decade, it's just been thought of as way too high risk," says Daria Hazuda, who does HIV drug discovery at Merck

Research Laboratories.

But safer methods of rousing latently infected cells could now be within reach. "In the last 10 years, there have been enormous new insights into transcriptional control mechanisms of HIV," says Jonathan Karn, who studies HIV gene expression at Case Western Reserve University in Cleveland. "That's been feeding indirectly into understanding latency and how you silence the virus and how it becomes reactivated."

Hazuda is now collaborating with Karn, Margolis, Richman, and other academic researchers to seek new drugs that can flush latent reservoirs. She's scouring Merck's shelves for promising experimental compounds as well as drugs that have already made it to market for other diseases. And she expects more companies to join in soon, partly because testing methods have lately made great strides. Powerful new drug screening assays have been introduced, and novel monkey and mouse models are available. New techniques in genomics and systems biology may also reveal biomarkers that allow researchers to gauge whether potential drugs have had an impact on transcription of the latent virus. "How do you show you've done something meaningful other than take people off drugs and pray the virus doesn't come back?" asks Hazuda. "That isn't a very scientific way to do things."

Even Siliciano, once a skeptic about eradication, now has his lab searching for antilatency drugs. "I've changed because I was really impressed by how easy it was to find compounds that would reverse latency in the test tube," he says.

TESTING HOPE
There is no cure for polio, hepatitis B, measles, chicken pox, influenza, and a long list of other viruses. Though the immune system and drugs can ultimately defeat many viruses, they are notoriously difficult to stop before they cause damage--especially a virus that integrates itself into

$$COL$$
chromosomes and can lie dormant for years. So it's no surprise that a cure still sounds far-fetched to many experts. Progress, if it occurs, will probably move in fits and starts, especially given the frequent disconnect between what happens in lab experiments and in humans. But the astonishing success of the Berlin transplant suggests that it's possible, and the limitations of the best available drugs show that it's necessary.

If Paula Cannon and collaborators at the City of Hope National Medical Center in Duarte, CA, receive a green light from the U.S. Food and Drug Administration, they plan to begin testing their gene therapy in a small number of HIV-infected adults who, like the Berlin patient, need ablation and a bone-marrow transplant to treat cancer--in this case, a B-cell lymphoma. The subjects' own stem cells will be modified with the zinc finger nucleases that disrupt the gene for the CCR5 receptor. The protocol will be extremely conservative. The patients' stem cells will be harvested four times, and as an insurance policy, the researchers will keep the first batch--the best ones--in reserve, untouched, in case something happens to the genetically engineered cells. Cannon also plans to stitch the zinc finger nuclease into an adenovirus to mimic a technique

$$COL$$
that has already received approval in Carl June's studies.

Cannon is confident that the human studies will prove the merits of the idea, even if it's only on a modest scale at first. "Our little piece of the puzzle is that we're trying to get zinc finger nucleases to work in stem cells and not do any harm," she says. If her research group can crack open the door, she predicts, colleagues will come rushing in to help find more effective, safer, cheaper ways to functionally cure HIV-infected people of all ages everywhere. "There's nothing like success to galvanize the community," she says. "If we can produce a one-shot treatment that basically means people don't have to take antiretrovirals, it's going to spread like wildfire."



Jon Cohen, a correspondent with Science, has written for the New Yorker, the Atlantic Monthly, and the New York Times Magazine. He is the author of Shots in the Dark: The Wayward Search for an AIDS Vaccine. His latest Book, Almost Chimpanzee, comes out in September.

Copyright Technology Review 2010
==========
Aug08 - Seroconversion
Mar10 - Diagnosis; cd4 690 - VL 19,000
Apr10 - cd4 600
May10 - VL 4,500
Jun10 - started Atripla ; VL 113
Jul 10 - UD vl, CD4 590
Aug 10 - UD, CD4 810, 52%
Nov 10 - UD, CD4 980

Offline Hellraiser

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #2 on: June 22, 2010, 01:48:12 AM »
Fantastic read here with interesting facts, hopefully some of this will pan out.  The latency activation was of particular interest, I'm wondering if the patients were suffering from some sort of cytokine storm or if it was something specific to the HIV.

Offline freewillie99

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #3 on: June 22, 2010, 11:02:43 AM »
What a great, great, article.  Thanks, Boze, for posting.  Made my month.
Beware Romanians bearing strange gifts

Offline Inchlingblue

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #4 on: June 22, 2010, 12:07:43 PM »
This is an excellent article, thanks for posting.

I love the part where they talk about Gero Hutter, the German doctor approaching the patient with HIV and Leukemia about doing the transplant with a CCR5-deficient donor:

"I told him we don't know what will happen, but there might be a chance we'll get rid of HIV," Hütter recalls. "He said, 'I don't care about this--I have no problem with antiretrovirals.' He was scared from his leukemia."
The patient changed his mind, and in February 2007, Hütter and his colleagues performed the transplant with stems cells that had the mutant CCR5.


Initially the guy didn't even want to try out this procedure, he did not mind having HIV! I guess if you live in a country where you have free access to health care and HAART, without having to sorry about insurance coverage, it's not that horrendous.

I also found it very interesting what one doctor said about the latent cells that harbor HIV:

"Latency is not a biological property of the virus," says Verdin. "HIV couldn't care less whether it becomes latent."

The latency does not happen because of the HIV, it's a biological mechanism separate from HIV. It was not clear to me before reading this; I used to think that maybe there was something HIV was doing to cause some of the cells to become latent.


I'm hoping that destroying the Berlin patient's immune system was not the reason he was cured and that it had more to do with the CCR5-deficient transplant.  Siciliano says,

As Siliciano cautions, it could be that destroying his immune cells would have cured the man no matter what replaced them.

There had been previous stem cell transplants performed on people with HIV that did not cure them. The big difference here was the CCR5-deficient donor. Siciliano must know this so it's strange he's saying that.
« Last Edit: June 22, 2010, 12:15:19 PM by Inchlingblue »

Offline tennisplayer56

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #5 on: June 22, 2010, 12:33:22 PM »
Well, according to this article:
http://www.haematologica.org/cgi/content/full/92/4/e56
there have been very few BMT's with regards to HIV in the past, and there are more than just the CCR5-deficient aspect. Many HIV patients who underwent BMT were only found to be HIV post-surgey, so were not on any kind of HAART, unlike this patient. Many other HIV patients who underwent BMT subsequently died, so the affect of the BMT on the HIV is unknown. There are also differences in procedure:
"Both patients had chronic GvHD and a non-myeloablative conditioning regimen was used. In our patient, we used a myeloablative conditioning regimen." 
I think this is why Sicillano believes it could be because of simply destroying the patients immune system that there the patient was cured, because there is real comparison that can act as a control for the CCR5-gene modification because all previous bone marrow transplants on HIV patients did not have a similar setting as to berlin patients (ie not being on HAART, patient dying, performing different BMT procedures, having a different form of cancer, etc).

BUT im still hopefuly and optimistic that it was the genetic therapy that cured him =).

Offline Inchlingblue

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #6 on: June 22, 2010, 12:55:25 PM »
The BMT could have bean part of the reason he was cured since he was shown to have dual-tropic virus before he was treated so it's a mystery why his CXCR4-tropic virus has not come back.

This doesn't necessarily mean that gene therapy alone can't do the trick. I guess only time will tell.
« Last Edit: June 22, 2010, 01:31:19 PM by Inchlingblue »

Offline tednlou2

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #7 on: June 23, 2010, 03:51:41 AM »
Very good read and thanks for posting.  About the guy in Germany functionally cured:  I've been surprised this hasn't made big news such as evening newscasts, 60 Minutes, The Today Show or something.  Has this guy and his doctors done interviews?  I would have thought this would have made big news, but I never heard about it until reading HIV websites.  Maybe I just missed it. 

I really hope this or other research comes to fruition.  When reading these things, I imagine the day when this happens.  I imagine the "Special Report" come across the TV.  I can invision that.  It would be like breaking news that we've found life on another planet.  Well, I hope the big HIV news is more likely than that. 

Offline mecch

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #8 on: June 23, 2010, 07:33:56 AM »
Maybe when we get it, we can call it the "Ho Vaccine" in honor of one of the first people to give us hope.

Plus a "ho vaccine" would just be too damn funny for the HIV cure.  :o ;D
“From each, according to his ability; to each, according to his need” 1875 K Marx

Offline Hellraiser

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #9 on: June 23, 2010, 08:48:01 AM »
Maybe when we get it, we can call it the "Ho Vaccine" in honor of one of the first people to give us hope.

Plus a "ho vaccine" would just be too damn funny for the HIV cure.  :o ;D

That's actually pretty damn funny.

Ted I was thinking the same thing, but it's really just a proof of concept that it CAN be done.  No one is under the impression that what happened with him is repeatable.  I doubt the guy really wants to talk about it either.

Offline stargate12

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #10 on: June 24, 2010, 04:20:30 AM »

I think this is why Sicillano believes it could be because of simply destroying the patients immune system that there the patient was cured, because there is real comparison that can act as a control for the CCR5-gene modification because all previous bone marrow transplants on HIV patients did not have a similar setting as to berlin patients (ie not being on HAART, patient dying, performing different BMT procedures, having a different form of cancer, etc).


As far as i know hiv was still detectable after  3/6  months from BMT...even his  CXCR4-tropic virus.

Offline Hellraiser

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #11 on: June 24, 2010, 08:45:05 AM »
As far as i know hiv was still detectable after  3/6  months from BMT...even his  CXCR4-tropic virus.

What they detected were antibodies.

Offline Inchlingblue

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #12 on: June 24, 2010, 11:08:31 AM »
What they detected were antibodies.

Yes, and even those they are finding fewer and fewer each time, they are expecting he will test HIV negative at some point since the antibodies are disappearing.

Offline ElZorro

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #13 on: June 24, 2010, 07:32:51 PM »
Wonderful post! Thanks! This made my day! I hope she gets her birthday wish!

Offline stargate12

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #14 on: June 25, 2010, 02:04:27 AM »
What they detected were antibodies.

I' m wrong and you are wrong too....on the 61st day after transplantation the semiquantitative assay showed  detectable proviral DNA.

Proviral DNA is created when the HIV virus enters a cell and uses the reverse transcriptase to make DNA copies of the RNA genome.  In few words.  : long-lasting hiv reservoirs, including  CXCR4-tropic virus.

New England Journal of Medicine February 2009.

Offline Hellraiser

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #15 on: June 25, 2010, 09:16:47 AM »
I' m wrong and you are wrong too....on the 61st day after transplantation the semiquantitative assay showed  detectable proviral DNA.

Proviral DNA is created when the HIV virus enters a cell and uses the reverse transcriptase to make DNA copies of the RNA genome.  In few words.  : long-lasting hiv reservoirs, including  CXCR4-tropic virus.

New England Journal of Medicine February 2009.

That was on day 61 after the procedure.  It's been 2 years.

Edit:  Here's a very good update article on thebody...
http://www.thebody.com/content/art53624.html

It details that they cannot find any virus and that his body is no longer producing new antibodies.
« Last Edit: June 25, 2010, 09:31:14 AM by Hellraiser »

Offline stargate12

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #16 on: June 25, 2010, 05:09:21 PM »
That was on day 61 after the procedure.  It's been 2 years.

Edit:  Here's a very good update article on thebody...
http://www.thebody.com/content/art53624.html

It details that they cannot find any virus and that his body is no longer producing new antibodies.

HIV dna detectable 61 days after BMT and chemio means that hiv reservoirs  were still in the body. Where did they go ? Simple vanish  including  CXCR4-tropic virus latent reservoirs ?


Offline Inchlingblue

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #17 on: June 25, 2010, 05:19:08 PM »
HIV dna detectable 61 days after BMT and chemio means that hiv reservoirs  were still in the body. Where did they go ? Simple vanish  including  CXCR4-tropic virus latent reservoirs ?




Do you have a link to where you read about detectable HIV after transplant? He did have two transplants, was this after the first one or the second one or both?

The whole point of trying this procedure is that if there was HIV after transplant it would not be able to take hold since his new T cells lack CCR5. What is a mystery is what about his CXCR4 virus? It's possible that the translant killed those off.

Have you read the updates on this case, including the link from thebody.com in Trey's post?

So he actually had a brain biopsy, in addition to biopsies of his intestines, liver, lymph nodes, bone marrow -- basically, every part of the body that can be biopsied. The best part in answering the Levy editorial was including his brain. All were negative for virus. There is no virus in this person's body out to two and a half years off of all anti-HIV drugs.

This is certainly a functional cure, in the sense that there is no need for anti-HIV drugs and no decline in the patient's immune system. But I would say that, at this point, with all the tests that have been done by scientists throughout the world that I've arranged to have samples sent to, that this patient is as close to a cure as anyone could possibly document -- apart from if the individual were to die and have every single part of every single body organ tested. There is no virus in this person's body.
« Last Edit: June 25, 2010, 05:22:14 PM by Inchlingblue »

Offline mpositive

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #18 on: June 27, 2010, 08:03:26 PM »
Great article.  Thanks for that! :)

Offline stargate12

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #19 on: June 28, 2010, 01:38:00 AM »

Do you have a link to where you read about detectable HIV after transplant? He did have two transplants, was this after the first one or the second one or both?


New England Journal of Medicine February 2009 ( it was after the second transplant )

Quote

There is no virus in this person's body.[/b][/color]

Only after months.

BMT and chemio were not strong enough to clear all hiv infected cells including  latent reservoirs with CXCR4-tropic virus.  Where is CXCR4 virus coming from latent reservoirs ?

Offline Inchlingblue

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #20 on: June 28, 2010, 11:20:03 AM »

BMT and chemio were not strong enough to clear all hiv infected cells including  latent reservoirs with CXCR4-tropic virus.  Where is CXCR4 virus coming from latent reservoirs ?

During the BMT many viruses are wiped out. It's possible the procedure was able to wipe out all the CXCR4 virus and only some of the CCR5-tropic virus was what was left. This virus was not able to take hold due to his new immune system lacking the CCR5 co-receptor. This is exactly what they were hoping would happen. This is the reason they went to the trouble of finding a donor with the delta-32 mutation, so that the remaining virus leftover would not be able to infect new cells.

The fact is he is still virus free and his levels of antibodies are getting lower and lower each time they check. As already mentioned, it's expected if he continues this way he will eventually test HIV-negative as the HIV antibodies continue to disappear.
« Last Edit: June 28, 2010, 11:24:23 AM by Inchlingblue »

Offline elf

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #21 on: June 29, 2010, 11:04:19 AM »
But we don't know, in some infections, antibodies are here to stay for good as a reminder of a past infection, although a person is disease-free.  ???
Let's have a Kiki!

Offline Inchlingblue

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #22 on: June 29, 2010, 11:15:59 AM »
But we don't know, in some infections, antibodies are here to stay for good as a reminder of a past infection, although a person is disease-free.  ???

True, but with HIV the antibodies are not enough to stop it so if this guy has no more virus there's no reason he would need those HIV antibodies so if they are going away then it sounds like a good thing to me.

Offline tennisplayer56

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #23 on: July 06, 2010, 03:38:28 PM »
hey this is may be a stupid question. but when they say this berlin patient was cured, can current technology detect whether the virus is completely whipped out? is he "undetectable"?

Offline Inchlingblue

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Re: Technology Review Jul 2010 - Can AIDS Be Cured?
« Reply #24 on: July 06, 2010, 05:11:51 PM »
hey this is may be a stupid question. but when they say this berlin patient was cured, can current technology detect whether the virus is completely whipped out? is he "undetectable"?

So he actually had a brain biopsy, in addition to biopsies of his intestines, liver, lymph nodes, bone marrow -- basically, every part of the body that can be biopsied. The best part in answering the Levy editorial was including his brain. All were negative for virus. There is no virus in this person's body out to two and a half years off of all anti-HIV drugs.

This is certainly a functional cure, in the sense that there is no need for anti-HIV drugs and no decline in the patient's immune system. But I would say that, at this point, with all the tests that have been done by scientists throughout the world that I've arranged to have samples sent to, that this patient is as close to a cure as anyone could possibly document -- apart from if the individual were to die and have every single part of every single body organ tested. There is no virus in this person's body.


LINK:

http://www.thebody.com/content/art53624.html

 


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