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Ever Changing and ongoing research
Oct 20, 2009

Dr. Bob, I was diagnosed on April, 28, 2009 and within weeks after being diagnosed and many labs test started Atripla with a VL of 23K and CD4 of 678. My last VL count was 90 and CD4 was almost 900. I have an excellent ID physician and primary care physician. Their sence of humor reminds me of the MANY MANY responses of yours I have read. By the way they speak very highly of "the body.com" as a valid source of upto date information. However, as I digress! My question is basic in theory but loaded in principle. So the question to you is: With the multitide of research that has transpired and continuing to transpire do you beleive that a medication will be developed in the comming years that will allow for the eradication of HIV in the latent cells that cause reinfection? I often think of going a licking the bark and nibbling on the roots of a walnut tree, but for some reason I belive I shall wait for your medical opinion prior to exhibiting such drastic bevavior that will land me in the psyc institute...

Response from Dr. Frascino

Hi,

Do I believe a medication will be developed "in the coming years" to eradicate (cure) HIV??? Sure! However, please note "in the coming years" means essentially any time in the future and the future is a very, very long time (unless you're one of those doomsday Armageddon wackos who insist the world will end in 2012, in which case the future is really not all that long). What I can say is that the "cure" is not on even the distant horizon as of yet, but we all continue to hope. But for now, I agree you should hold off on the tree licking and root nibbling. (See below for information from the archives pertaining to a cure for HIV/AIDS.)

Dr. Bob

opinion (CURE 2009) Aug 13, 2009

hi Dr Rob,

i am newly diagnosed HIV1 positif, and i have a small question to ask, with all the technology and the increasing development in the medcation fieled do you think that one day their will be a cure to the HIV, if yes please explain for me the theory that you have in mind, and if no, what makes it impossible to find that cure, knowing that the hardest deseases were cured nowadaya. i know sounds like a stupid question, but according to the statistics in many diffrent field human race is developing very fast comparing to perviouse century. sorry to waste your time on this question maybe to you it sounds stupid but to me its not thank you very much for your time

Response from Dr. Frascino

Hi,

Check out the archives of this forum. We have a whole chapter devoted to "HIV cures." I'll reprint below some information from the archives.

Let's all be here for the cure, OK?

Dr. Bob

Cure for HIV/AIDS (CURE 2009) (CURE 2009) Feb 19, 2009

Hi, I have been wondering why it is so difficult for HIV/AIDS cure to be found especially for Americans who nothing is impossible for. I am from Africa living with HIV. Would there ever be a cure for this deadly disease and when?

Response from Dr. Frascino

Hello,

See below. I have nothing new to add at this time.

Dr. Bob

cure (CURE) Feb 6, 2009

what are the limitations in finding the cure for hiv

Response from Dr. Frascino

Hi,

Time for an HIV cure reality check, as this question comes up frequently. Care to guess how many viral disease we can cure today with medical therapy? One! That's right; only one: hepatitis C. And even hepatitis C is cured only very infrequently! Sure we can prevent some viral illnesses, like mumps, measles, rubella, etc. And some viral infections can subside but remain dormant in the body forever or have periodic flare-ups (herpes, EBV, for example). Many viral infections resolve spontaneously over time, such as the flu or common cold. And of course there are those viruses that can plant us six feet under very, very quickly, such as Ebola. HIV is a very clever and tricky virus indeed. It hides out in the genetic material (DNA) of some of our longest-lived human cells. This makes it extremely difficult to wipe out HIV without wiping out the human host at the same time.

Lots of folks get frustrated that a cure hasn't been found. Conspiracy theorist crackpots think that pharmaceutical companies or the government are withholding the cure to make money. This, of course, is pure lunacy. After all, there are loads of other chronic incurable diseases we haven't yet conquered, such as asthma, diabetes, Parkinson's, Alzheimer's, high blood pressure, arthritis, etc. Some of these illnesses, like HIV, are becoming more manageable as we learn more about them and develop new and novel therapies. Will there ultimately be a cure for HIV? I, for one, certainly remain hopeful.

Dr. Bob

In our life time (CURE, 2009) Feb 4, 2009

Hello Dr.Bob just wanted to tell u that u are doing a good job on here. My question is do u think that in our life time they well ever find a cure for HIV. I'm HIV+ for 2 years now and eveyday I'm praying and looking for a cure. Its like eveyday my hopes keep getting smaller and smaller. Should I be waiting or should we as HIV+ just let the cure fall into our laps someday.

Response from Dr. Frascino

Hi,

I strongly doubt a cure for HIV/AIDS will fall into our laps! The way to the cure is scientific research. This unfortunately requires significant funding as well as considerable talent and knowledge. And this type of basic science investigation takes considerable time. Should we be optimistic? Well I'm not only a "glass half full" kind of guy, but actually more of a "glass overflowing" type. I remain very optimistic we will eventually make HIV/AIDS nothing more than a bad memory. I'll reprint below some information from the archives that discusses progress toward "the cure"!

Dr. Bob

RESEARCH FOR A CURE... Apr 5, 2008

- Why does not the United States and other wealthy countries join up and spend their billions to find a cure meaning elimination of the virus ?

- A third of the money spent on PEPFAR could stroke up the research engine and a program of the dimensions of the moon shot could do it . Atleast even if we do not succeed the science spinnoffs would be enormous. - Why do the aids activists the US not pursue this goal ? Have they given up hope for a cure..

Response from Dr. Frascino

Hello,

Have we given up hope for a cure? Absolutely not! See below!

Dr. Bob

The Cure: Why, Whether, How and When

By Martin Delaney

April 2008

More than three years ago, Project Inform kicked off a campaign to refocus the attention of the patient, activist and research communities on the need for a true cure for HIV disease. The success of combination therapy and treatment simplification seemed to have created a wave of complacency and a sense that, except for side effects, HIV treatment was finally "good enough." Project Inform has challenged this view ever since. Though the effort was sometimes ridiculed as nave, a number of influential groups and researchers have now joined the campaign.

Today more people than ever agree that the current standard of lifetime maintenance therapy is not an adequate solution to the HIV epidemic. Several factors made this conclusion more obvious than ever. This article examines four issues about the notion of curing HIV disease: (1) why the goal of curing HIV disease has become so critically important; (2) whether a cure is feasible given current and near future technology; (3) what "cure" means and how it might be achieved; and, (4) when this might be possible. The article also closes with new information about efforts now underway toward reaching this goal.

1. Why Is a Cure so Important? This may seem obvious to just about anyone with HIV disease, but it has not always been so. Today's regimens offer dramatically better outcomes than what people typically faced earlier in the epidemic. It might be easy for some to think that the problem of HIV has largely been solved. Not quite. Not even close.

Thankfully, the days of a short-term death sentence are well behind us. With good care and treatment, it's fair for people with HIV to expect to live out a relatively normal lifespan. Missing from the greatly improved picture are the ways in which HIV disease still complicates the lives of those affected as well as its costs to both the individual and the public.

Today, HIV treatment means a lifetime of using multiple, expensive medications whose long-term side effects can't be known until they have actually been used long-term. Today's drugs are easier to use and appear far less toxic, but only a few have been used for 10 or more years. We have yet to learn what the consequences will be of 20 or 50 years of use.

Another thing typically overlooked is the lifetime cost of treatment which currently averages between $12,000-$25,000 a year for relatively healthy people with HIV, and much more for those in advanced stages of disease. While these costs have been met in the short-term, we're only beginning to look at the lifetime costs of being on regimens for up to 50 years. It's simple: do the math! And what about the developing world, where roughly 90% of the world's cases of HIV occur? Despite massive infusions of money, and despite reducing the costs of drugs to virtually that of their raw materials, efforts still only reach a modest percentage of the people worldwide who need treatment.

The US committed more than $15 billion to HIV treatment in developing countries over the last five years through the PEPFAR program. The World Health Organization, Global AIDS Fund, Clinton Foundation and many smaller groups along with support programs from the pharmaceutical industry have made enormous additional contributions. The reach is still too small and the amount of money needed must be increased many times over to reach even the most vulnerable parts of the infected population.

It has long been hoped that this would only be temporary; that we would have a vaccine and the numbers of people infected each year would finally begin to drop. Sad to say, but the search for a vaccine hit a wall in the last year. In many ways, we may now be no closer to a vaccine than we were 20 years ago. Some of the most prominent scientists in the world are warning us that a vaccine may never be possible due to HIV's unique properties.

At the very least, if there is to be an HIV vaccine, we currently have no idea how to make one. Similarly, great hope was invested in using microbicides -- gel-like compounds applied to the areas of sexual contact that hopefully block HIV infection. But so far these have proven about as effective as vaccines, which is to say "not at all."

Thus, when we take a sober look at the fight against HIV in the developing world, the prospects of lifetime therapy don't look so good either. First, the expenditures by wealthier nations will have to drastically increase, and then these sums must be sustained for the next 50-100 years, assuming there's no vaccine in the near future. We must ask: how likely will developed nations continue this level of support for as long as it's needed?

Sadly, the answer is not very likely. For one, there's little precedent for sustained medical effort in developing nations, let alone one as expensive, difficult and lasting as fighting HIV is. Secondly, the costs are so large they may not be sustainable at all. Even the great private funds like taht of Warren Buffet will be bankrupted over time by this fight.

In short, lifetime therapy is not a realistic solution for HIV disease even in the US and Europe let alone the developing world. The situation can only worsen if unexpected long-term side effects appear over time.

It should be abundantly clear: the only way to effectively conquer the epidemic is to cure the disease. We cannot coddle the virus with a lifetime of drugs. People with HIV should be enormously grateful to all those who have contributed to developing the drugs we have today. Millions more would have died without them. But their utility is limited and they're not a true long-term solution. The goal of fighting HIV for the first 25 years was to create and distribute effective anti-HIV drugs. The goal of the coming years must be to get people OFF the drugs and back to a state of normal health.

2. Is a Cure Feasible? It is one thing to conclude that a cure is needed, and perhaps it's the best and only real solution to the epidemic. It is quite another to say that it's possible to create one.

Many scientists argue a cure is unrealistic with any conceivable technology. They quickly insist that a cure requires the complete eradication of HIV. Every copy of it must be prevented from infecting a cell, and every cell that already contains HIV must die off or be destroyed. Otherwise, they believe, the infection will just start up all over again.

While this sounds reasonable at first, is it necessarily so? It is important to ask scientists, "Just what data support this? What study or observation concludes that you have to eliminate every last copy of HIV or infected cell to reach a point where it's no longer a problem?" There are no such data, no such studies. It is a belief, not a scientific fact.

The hints we have from data largely suggest that the opposite may be true. Many viruses peacefully co-exist in the human body, though in some cases they can be highly destructive. Two good examples are CMV and JCV. CMV can cause blindness and death; JCV can cause a horrible form of dementia that leads to death. Yet each is quietly present at low levels in most people and does little or no harm except in rare circumstances.

What about HIV? In primates, the equivalent of HIV is called SIV, and it often replicates freely yet does not cause harm or become AIDS. It's how the immune system reacts to it that causes the harm. Moreover, we know there are literally thousands of humans with HIV who, due to a combination of factors, either maintain only low levels of HIV or simply don't get sick from it. They may be a small minority, but they prove the point: HIV, even in the absence of treatment, is not always destructive.

The data simply do not support the notion that the only way to survive HIV is either through lifetime therapy or by complete eradication of virus. It would be ideal to rid the body of HIV, but an effective cure may NOT require this. If anything, the data suggests the opposite.

We see people repeatedly exposed to HIV who never become productively infected. We see that reducing, though not eliminating, virus in a pregnant woman almost completely eliminates the risk of her passing the infection onto her child. We know that true long-term non-progressors, or elite controllers, sustain some level of HIV infection but show little evidence of clinical illness.

Perhaps a harmful case of HIV requires a certain level of virus before it becomes destructive. Maybe treatment can push the level of virus low enough that it no longer matters. Possibly some of the new properties shown by drugs like CCR5 antagonists and integrase inhibitors may change the underlying conditions that make harmful HIV replication happen.

Dr. Steven Deeks, a key researcher from the University of California, summed it well at a recent Project Inform Update Town Meeting when he said, "Beware of grey haired scientists who tell you something is impossible." He is hardly alone.

There's a growing cadre of young investigators at universities, the NIH and drug companies who believe a cure is indeed feasible, and perhaps sooner than many think. It is instructive to remember that shortly after HIV was found to be the cause of AIDS, some researchers claimed, "It will be impossible to treat this disease at all." Within 21 months, the first drug was approved by the FDA. Little more than 20 years later, scientists claim that people with HIV and access to treatment could expect to live a normal life span. A cure is not only possible; it is the next step in HIV research.

3. How Can HIV Be Cured? It is admittedly premature to pronounce that one approach or another is the most likely avenue to curing HIV. Instead, there are a number of possibilities. What we need are some serious programs to develop and test them. So far, the most widely tested approach has used just antivirals, alone or together with another kind of drug to try to eradicate HIV.

Scientists back in 1996 thought it would be enough to simply give people the strongest antivirals for several years in a row and this would gradually eliminate even the last copies of HIV. They were wrong, but this led to the discovery that HIV was being sustained, in relatively small amounts, in "reservoirs." These were generally inactive cells, like memory T-cells, which the immune system only rarely activates and uses. They're largely unaffected by HIV drugs and the immune system. For some reason they can only be reached when they are activated.

This led to a second approach, one that was predicted in the 1980s. It also used the most potent antivirals and added a second type of drug to activate these reservoir cells. This ultimately proved dangerous, as it activated all the cells in the body. Still, some scientists believe we haven't given this approach a fair trial. They argue that perhaps we need to use this approach more slowly, but repeatedly, in hopes of reaching all the cells in the reservoirs, but not all at once.

Although neither approach succeeded, they showed that when patients were treated in this way, they would sometimes remain free of active replication for a month or longer without therapy. A similar early attempt used the immune modulator IL-2, which is T cell stimulator, to achieve this goal. This too seemed to delay the return of viral replication in people whose antiviral treatment was interrupted, but it eventually failed.

Thus, attempts at eradication have neither succeeded, nor completely failed. Several studies are now underway to further test eradication theories by using the new integrase inhibitor drugs. Their different mechanism of action offers some theoretical benefits compared to previous antivirals. Remember, though, that we really don't know whether a "cure" actually requires complete eradication.

A recently reported case study from Germany described what happened when a patient was given a stem cell transplant, for treating cancer, by using cells from a donor who lacked the genes that cause the body to make the CCR5 receptor favored by HIV. This case study is described in more detail on Project Inform's website in our coverage of CROI 2008.

More than 300 days after the transplant and any use of antivirals, the patient still shows no evidence of HIV replication, either by standard viral load testing or a more sensitive test that measures what's called pro-viral DNA. Though the investigators are not calling it a cure, they continue to follow the patient to see whether or when HIV replication might restart.

At the very least, it seems to prove the concept that when viral levels are greatly reduced, even if not eliminated completely, the body seems to keep HIV well in check for long periods without antivirals. It would be difficult to find enough donors who have this very special type of genetic mutation, so this exact procedure is not practical for large numbers of people. A similar goal could be achieved through gene therapy, something which eventually could be applied to large numbers. Other types of gene therapy also offer hope in the pursuit of a cure.

Yet another approach seems to offer hope, even if it proves necessary to go after every cell that has been infected by HIV. A German group revealed a new technology, on a laboratory level, which is able to extract viral genetic sequences that have been integrated into human cells. It's a long way from being a practical therapy, but again, it shows proof of the concept.

Other scientists are working on ways to suppress the inflammatory processes triggered by HIV infection. Some believe that it is inflammation rather than any unique activity of HIV that makes it harmful. They believe it causes harm primarily because it causes cells to release inflammatory proteins, which in turn harm the body. If this is correct, turning down or turning off the inflammation may be enough to change HIV into a harmless virus.

These and other approaches all rely on a simple definition of what curing HIV must mean. Cure, in this way of thinking, may not mean absolute elimination of the virus. Rather, it simply requires reaching a state where either there's no measurable HIV replication despite withdrawing therapy, or where the immune response to HIV is changed in ways that no longer harm the body or immune system.

A cure also cannot be expected to automatically repair any damage done to the immune system when HIV was active. It would be great if that could be achieved, but it's not a standard we demand of other cures. Sometimes a cured disease leaves damaged tissue or cells behind. Sometimes the body fixes them over time; sometimes it doesn't. Antiviral drugs aren't completely fixing the immune system now, so we cannot demand that a cure will do it either.

4. When Can a Cure Happen? This question is impossible to answer. At best, prediction is a tricky business. However, a number of the more enthusiastic researchers seeking a cure believe that the solution may be closer than most believe. Claims that it won't be possible until far in to the future are based on the false definition of cure, the one that demands absolute eradication. Once we realize that this is not required, the cure doesn't seem so very far away.

It's now routine to reach HIV levels below 50 copies. Studies with new drugs are now using a test that measures down to 5 or 10 copies, and there's evidence that the drugs are succeeding at this level. Researchers will need to retest various eradication approaches using these new therapies. We really don't know what happens when HIV is suppressed this low for long periods. Similarly, a few first generation gene therapy studies are well underway and near completion. These may not be the total solution but could well point us there, as does the German stem cell transplant program. The most optimistic researchers we have spoken to believe we will see the first evidence of a cure in as soon as 5 to 10 years.

A few argue that it has already happened, but our ability to see and measure it lags behind. It is even possible the immune system itself has done the job in some cases, but we just don't know it. Why? Because once a person gets truly well, they are seldom studied. We simply would not know if there have been people all along for whom the natural immune response has been sufficient.

We believe this process can and must be accelerated. It currently receives very little funding -- just a tiny fraction of the amount spent developing new antivirals. We are aware of only two pharmaceutical companies that are actively pursuing cure-based research. Merck has a lab dedicated to studying eradication in the same systematic way they develop a new drug. Tibotec/J&J is already engaged in a very interesting gene therapy study that may help point the way. We'd like to see every drug company invest in this area, if for no other reason than the fact that it might offer the last hope for big profits in the fight against AIDS.

There are now 24 antivirals on the market. Each gets only a modest portion of the revenue generated by only about 10% of people with HIV. If the lure of profits is what it takes to generate interest in the cure, so be it. While a cure would certainly end the drug companies' revenue stream from lifetime therapy, several have argued that there are far more profitable areas of medicine and drug development than HIV. They would make more money working in those areas once their patents in HIV expire.

Given the failure of vaccines and the difficulties faced in microbicide development, along with the prohibitive costs of lifetime therapy, we believe research funding must be redirected toward the kind that can result in a cure. This will require a large change in how research is funded, and it requires new insights from basic science as well as clinical research.

Efforts are underway to make this happen. In December 2007, more than 125 scientists from around the world came together in a meeting dedicated to unraveling the challenge of HIV persistence and eradication. These scientists, along with a few activists and foundation representatives, are committed to this type of research.

amfAR has already issued a series of program grants for work in this area. A collaboration of community groups is also organizing a scientific meeting that will take place in the fall to develop plans and strategies to enhance and support this research. TAG (Treatment Action Group), amfAR, FAIR, The Forum for Collaborative HIV Research and Project Inform have banded together to organize and help fund this meeting, which may be the first of several. amfAR is considering a second round of grants to support such work, and FAIR (the Linda Grinberg Foundation for AIDS and Immune Research) will fund another group of proposals.

Collectively, we hope to further influence the Division of AIDS at the National Institute of Allergy and Infectious Diseases to increase its commitment to this type of research.

As we shift our thinking in pursuit of a cure, we will not abandon interim needs. There is still a need for better and less toxic antivirals. There's a profound need to figure out how to make the best use of the new drugs we've recently gained. Project Inform is pursuing these needs on a separate but parallel track through another scientific conference we're organizing for the fall, called HAART 2.0. This meeting will help develop strategies for testing new paradigms of treatment with current drugs. These include such things as one- and two-drug regimens, eliminating the most toxic agents, and reducing the use of drugs that harm the liver or heart. Some of what we learn through that process will not only benefit patients in the short-term but will also contribute toward the final push for the cure.

A Personal Comment As many of you know, I (Martin Delaney) officially retired from my programmatic role at Project Inform in January, but I have not left AIDS work. I am committed to making this focus on a cure the core of my work in the final chapters of my life. Like others at Project Inform and many other organizations, I believe that we can and must find a real cure. There is no other real solution on the horizon. This is as true for the US and Europe as it is for the developing world. We won't have a cure unless we believe in it and pursue it as our primary goal. We're going to have a cure, and it will happen in our lifetimes.

Funtional Cure Jan 13, 2009

Hello

I would like to know what is a "funtional cure" for HIV? I've read before somewhere that a funtional cure my be possible before a total (eradication)cure of HIV from the body.

Response from Dr. Frascino

Hi,

Basically there are two types of potential "cures" for HIV: sterilizing and "functional." A sterilizing cure is synonymous with "viral eradication" (i.e. the elimination of every viral particle from an infected person). This has been achieved in some folks who had hepatitis C but never ion someone infected with HIV. Because of HIV's uncanny ability to persist and replicate, even after a decade or more of fully suppressive therapy with potent antiretroviral drugs, it was felt for some time now that a sterilizing (eradication) cure was the only real cure. Recently we've begun to discuss another type of "cure," a functional cure.

A "functional" cure would mean that even though HIV was not totally eliminated from the body, an HIV-infected person would be able to live and be healthy long-term without the need for antiretroviral drug treatment.

Dr. Fauci, the head of the National Institute of Allergies and Infectious Diseases at the National Institute of Health (NIH), discussed the potential of a functional cure for HIV at his presentation at the International AIDS Conference in Mexico City in August of last year. The potential model for a functional cure would involve very early and very aggressive HIV-drug treatment, possibly combined with HIV-specific immune-based therapies. This model would require diagnosis very soon after infection (days) and the access to very aggressive therapies. I should point out the concept of a "functional cure" is still experimental at this time. However, it is encouraging to hear someone of Dr. Fauci's status talking about a cure. Stay tuned to The Body. We'll keep you posted as this story evolves.

Dr. Bob

Funtional Cure Jan 13, 2009

Hello

I would like to know what is a "funtional cure" for HIV? I've read before somewhere that a funtional cure my be possible before a total (eradication)cure of HIV from the body.

Response from Dr. Frascino

Hi,

Basically there are two types of potential "cures" for HIV: sterilizing and "functional." A sterilizing cure is synonymous with "viral eradication" (i.e. the elimination of every viral particle from an infected person). This has been achieved in some folks who had hepatitis C but never ion someone infected with HIV. Because of HIV's uncanny ability to persist and replicate, even after a decade or more of fully suppressive therapy with potent antiretroviral drugs, it was felt for some time now that a sterilizing (eradication) cure was the only real cure. Recently we've begun to discuss another type of "cure," a functional cure.

A "functional" cure would mean that even though HIV was not totally eliminated from the body, an HIV-infected person would be able to live and be healthy long-term without the need for antiretroviral drug treatment.

Dr. Fauci, the head of the National Institute of Allergies and Infectious Diseases at the National Institute of Health (NIH), discussed the potential of a functional cure for HIV at his presentation at the International AIDS Conference in Mexico City in August of last year. The potential model for a functional cure would involve very early and very aggressive HIV-drug treatment, possibly combined with HIV-specific immune-based therapies. This model would require diagnosis very soon after infection (days) and the access to very aggressive therapies. I should point out the concept of a "functional cure" is still experimental at this time. However, it is encouraging to hear someone of Dr. Fauci's status talking about a cure. Stay tuned to The Body. We'll keep you posted as this story evolves.

Dr. Bob

lack of superinfection and 'cure' Feb 6, 2009

hi doc. it appears there's been some recent reevaluating regarding the topic of superinfection, written about on this very site.

a study lends credence to the theory that not only does superinfection not occur, but 2 poz partners become immune to the other's strain. Couple this with the study of the prostitutes who stayed healthy until they STOPPED exposing themselves with new HIV, and couple that with the fact that the initial natural immune response to hiv is very good,... we can come to a theory:

treatment for poz people should include perpetually re-exposing the patient to hiv.

Its like that Grindhouse movie where Bruce Wilis and the soliders are zombies, but they stay human as long as they continually intake the virus that causes zombi-ism. Thoughts?

Any studies exploring giving a patient HIV over and over? Are we on to somethign? Thank you, sir.

Response from Dr. Frascino

Hello,

You want to design a clinical trial in which an HIV-negative person is given repeated exposures to HIV based on a Bruce Willis Zombie movie in which he retains his humanness by continually exposing himself to the virus that causes "zombism"???? Oh my. That has as much chance of getting through an investigational review board as Dubya has of simultaneously winning Nobel prizes for peace, economics and rocket science.

I assume your theory is based somewhat on the intriguing and slowly evolving story about HIV-negative men in long-term relationships with HIV-positive men developing an antibody response in saliva that may inhibit HIV infection. Investigations are underway studying IgA1 antibodies in HIV-negative men in magnetic relationships. To jump from these preliminary reports to a clinical trial such as you suggest is, of course, a quantum leap of faith that no one in their right mind should take, even zombie-ized Bruce Willis. Stay tuned to The Body. We'll keep you updated as we unlock more mysteries related to the immune response to HIV and the potential of induced protective immunity.

Dr. Bob

Bone Marrow Transplant Feb 3, 2009

Hello Dr. Bob, I have a question. I read about a man in Germany who had a bone marrow transplant and hasn't needed HIV meds for 2 years now. He hasn't been cured obviously, but apparently the bone marrow transplant has helped him combat the virus somehow. Is this a possible treatment for HIV, or is this man a needle in a haystack? Have you heard anything about this, and what are you thoughts on it?

Response from Dr. Frascino

Hi,

As with so very many other questions (95% plus!), the answer to your question was already waiting for you in the archives. See below.

Dr. Bob

First claim of aids cure from the scientific community and qualified medical doctors! (BONE MARROW TRANSPLANT,"FUNCTIONAL CURE" Nov 14, 2008

Hi Dr. Bob,

While I dont have hiv nor have been at risk, I follow your posts just for your great sense of humour and expert knowledge.

Anyway, the news just broke that German doctors have had a breakthrough which might be a big step in finding a CURE for aids.

here are the links: http://ap.google.com/article/ALeqM5hwlpMzO2z0voECw2T4MfOPkOEXNAD94DSGLG0

http://www.dw-world.de/dw/article/0,2144,3787690,00.html

Am sure everyone would be eager to know your opinion.

Thanks,

Response from Dr. Frascino

Hi,

See below.

Dr. Bob

bone marrow transplant??? Nov 14, 2008

Hi Doctor,

My boyfriend just showed me this article http://www.usatoday.com/news/health/2008-11-12-aids-cure_N.htm Is this possible true? what do you think about it?

Response from Dr. Frascino

Hi,

The elusive search for an HIV/AIDS cure has been replete with disappointments over the past 27 years. However, the holy grail of viral eradication ("cure") must remain our ultimate goal. The case report of a 42-year-old American living in Berlin who appears to have had a "functional cure" of his HIV by undergoing a bone marrow transplant for his leukemia may well point the way to new avenues of research aimed at a cure. However, it's worth noting that in 2007 there was a case report of an HIV-positive French man who underwent bone marrow transplantation to treat leukemia and subsequently had an undetectable HIV plasma viral load. His HIV unfortunately rebounded when he briefly stopped taking his HIV meds after the transplant. The young man died when his body rejected the transplanted bone marrow one of the several serious risks associated with bone marrow transplantation. My take on all this is very cautious optimism: I'm hopeful that gene therapy will eventually become a safe and effective therapy.

Dr. Bob

Dr Bob,check this out!!! Nov 14, 2008

a german doctor cured hiv positive american living in berlin http://news.bbc.co.uk/1/hi/health/7726118.stm

Response from Dr. Frascino

Hi,

This really is a fascinating and highly unusual case. Hopefully it will lead to a resurgence of interest in gene therapy and other efforts aimed at a cure. The particular treatment the Berlin patient underwent would be appropriate for only very few highly selected individuals. The procedure also carries significant risks, including a 30% chance of death. Plus, there may well be unanticipated short- and long-term consequences from the treatment.

I'll print some additional information below. I'll also continue to follow this story as it evolves and report back any promising findings.

Be well.

Dr. Bob

NOVEMBER 7, 2008 A Doctor, a Mutation and a Potential Cure for AIDS A Bone Marrow Transplant to Treat a Leukemia Patient Also Gives Him Virus-Resistant Cells; Many Thanks, Sample 61By MARK SCHOOFSArticle Comments more in Health (See Corrections & Amplifications item below.) 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.

Sixten Koerper Dr. Gero Hütter isn't an AIDS specialist, but he 'functionally cured' a patient, who shows no sign of the disease. "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. Write to Mark Schoofs at mark.schoofs@wsj.com Corrections & Amplifications The Foundation for AIDS Research, which uses the acronym amFAR, is the name of the nonprofit group cited in this article. The name of the group was incorrectly given as the American Foundation for AIDS Research.



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