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HIV infection cure? Was told on CNN. What do you think? Mommy of three. (BERLIN PATIENT, 2010) (TIMOTHY BROWN, THE BERLIN PATIENT, 2010)
Dec 18, 2010

Hello my beloved Dr. Bob. I hope you are feeling wonderfully. I am writing because I came upon this article today on CNN's news page. I think I know you enough to figure out what you think about it, but truly want to hear all you have to say about it. I send you now as always, much love from your sister,

MOMMY OF THREE.

HIV infection cure? Sorry. Forgot to attach article. Mommy of three. (Submitted Dec 15, 2010)

Researchers report possible HIV infection cure; others cite dangersBy Tom Watkins, CNN December 14, 2010 10:46 p.m. EST

Demonstrators march in Vienna, Austria, as part of the 18th International AIDS Conference on July 20, 2010.STORY HIGHLIGHTS A Berlin man has been off anti-AIDS medication for 3-1/2 years But the stem-cell transplant credited for ridding him of HIV is costly, dangerous "This is probably a cure, but it comes at a bit of a price," says one AIDS doctor (CNN) -- Researchers in Germany are reporting that they may have cured a man of HIV infection. If true, that would represent a scientific advance, but not necessarily a treatment advance, said researchers familiar with the work.

In the study, published last week online in the journal Blood, researchers at Charite-University Medicine Berlin treated an HIV-infected man who also had acute myeloid leukemia -- a cancer of the immune system -- by wiping out his own immune system with high-dose chemotherapy and radiation and giving him a stem-cell transplant. Stem cells are immature cells that can mature into blood cells.

At the time of the transplant, which occurred in February 2007, he stopped taking anti-HIV medications.

Thirteen months later, after a relapse of the leukemia, he underwent a second round of treatment followed by another stem-cell transplant from the same donor.

The donor's stem cells contained a rare, inherited gene mutation that made them naturally resistant to infection with HIV, according to the authors, led by Kristina Allers, who hypothesized that HIV would nevertheless rebound over time. But that has not happened.

After three-and-a-half years off of anti-HIV drugs, the patient shows no sign of either leukemia or HIV replication and his immune system has been restored to normal health, the researchers reported, concluding, "our results strongly suggest that cure of HIV has been achieved in this patient."

But AIDS researchers predicted the report will have little impact on practice.

"This probably is a cure, but it comes at a bit of a price," said Dr. Michael Saag, professor of medicine and director of the University of Alabama at Birmingham AIDS Center.

"For him to receive the donor cells, his body had to have all of his immune system wiped out" and then receive a bone marrow transplant, Saag noted. "The Catch-22 here is that the best candidates for a cure, ideally, are people who are healthy" and don't have leukemia.

The treatment associated with wiping out the immune system "is very hazardous," he said in a telephone interview.

"Even if somebody doesn't die from a transplant, there are complications that make it very unpleasant for people to live with," he said, citing graft-versus-host disease, where the infused donor cells attack the body. In a number of cases, the transplant proves fatal.

The study is a proof of the concept "that our understanding of HIV biology is correct, and that if you eliminate -- not just in theory but in practice -- all of the cells in the body that are producing HIV and replace them with uninfected cells, you have a cure," Saag said.

But remaining infected with HIV is not always associated with the same grim outcome that was the norm prior to the mid-1990s, when more effective anti-HIV drugs were developed, he said.

"We can keep people alive for a normal life span," he said. "That means a 25-year-old diagnosed today with HIV has a reasonably good chance of living to 80, 85, 90."

Further limiting the treatment's potential appeal is the fact that it could cost hundreds of thousands of dollars for each patient who gets it, he said.

"It's not going to be applicable unless they develop leukemia or lymphoma and need a bone-marrow transplant,"Saag said.

Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, called it impractical. "It's hard enough to get a good compatible match for a transplant like this," he said in a statement. "But you also have to find (a) compatible donor that has this genetic defect, and this defect is only found in 1% of the Caucasian population and 0% of the black population. This is very rare."

But HIV itself is not. According to the World Health Organization, 33.4 million people worldwide have the virus that causes AIDS.

Response from Dr. Frascino

Hi,

See below!

Happy Healthy Holidays to you and yours.

Dr. Bob

Doctors in Berlin claim to have found a "cure" for HIV (BERLIN PATIENT, 2010) (TIMOTHY BROWN, THE BERLIN PATIENT, 2010) Dec 18, 2010

Hi Dr. Bob.

I was on the internet and ran across this article:http://www.aidsmap.com/page/1577949/ I was wondering what you think about its potential and whether you think it holds up scientifically. I'm currently in medical school and am amazed by HIV. This also makes me hopeful because I exposed myself to HIV through unprotected heterosexual vaginal sex (I'm the guy) and am getting tested today. I have a very bad feeling but this has made me hopeful that even if I am infected a cure may be found in my lifetime.

Take care and hope you are in good health!!

Response from Dr. Frascino

Hello,

We have been following the story of "The Berlin Patient" for a number of years. Due to a recent publication in the medical journal "Blood," the story has resurfaced with great fanfare. So it's time for an update on not only what happened, but also on what it all means. You asked if I thought the story "holds up scientifically." Yes, it does, but most people don't understand the whole story or it's potential relevance. Consequently, let me recap briefly.

Timothy Brown is an American with acute myeloid leukemia (AML) who was treated at the Charite-University Medicine Berlin in 2007. Mr. Brown developed leukemia after having been diagnosed HIV positive. Talk about bad luck! But his luck then changed big time! The treatment for AML involves chemotherapy, radiation therapy and stem-cell transplants. In essence the doctors needed to completely wipe out Mr. Brown's existing immune system and attempt to reconstitute it from scratch using donor stem cells. This is a very dangerous procedure with a significant morbidity and mortality rate. It's also incredibly expensive -- hundreds of thousands of dollars! (And that's if all goes well).

So how does this relate to an HIV "cure"? Glad you asked. This part gets a bit confusing, so pay attention. HIV needs certain receptors on cells in order to gain access to and infect immune cells. The most common type of receptor is termed "CCR5." If a cell doesn't have a CCR5 receptor, HIV viruses that require this receptor are essentially locked out. Put another way, the person lacking CCR5 receptor is immune to HIV virus requiring CCR5 to gain access and infect immune cells. A very small portion of the general population is lucky enough to have a mutation of the CCR5 gene that they inherited from both their parents (homozygous). Timothy Brown received a stem-cell donation from a donor who had the mutation and luckily his stem-cell transplant was eventually successful. (He had a relapse of his leukemia 13 months after the initial treatment and required a second round of treatment including another stem-cell transplant from the same donor.) As his new immune system grew, it too had the CCR5 mutation. Consequently, HIV-requiring CCR5 couldn't enter or infect new cells. Mr. Brown has now been off antiretroviral drugs for 3.5 years and shows no sign of HIV. It's an amazing story. But before you decide to fly to Berlin and ask for the same treatment, it's important to realize the following:

1. Not all HIV viruses require CCR5 to infect cells. Some viruses use an entirely different receptor (CXCR4).

2. Wiping out your immune system is extremely dangerous carries a significant risk that you could wind up dead as a doornail. It only makes sense when you have a disease like acute myeloid leukemia, which is already killing you quite rapidly.

3. Most folks do not have several hundred thousand dollars lying around, unless they're among the top 1% of Americans who will benefit from extending the Bush tax breaks for gazillionaires.

4. Finding someone with the delta 32 mutation that blocks CCR5 viruses from entering cells is extremely difficult. According to Tony Fauci, the head of the National Institute of Allergy and Infectious Diseases, only 1% of Caucasians and 0% of blacks have the mutation. Plus, you would need to find not only a donor with the mutation, but also a donor that was a "match" for you (immunologically compatible).

The bottom line is that this treatment will never be ready for prime time. It may, however, open new doors into research toward a cure that could. As always, we'll keep you posted as this story continues to evolve.

Dr. Bob

Possibility of a Cure? Dec 31, 2008

Greetings Dr. Bob!

I am a long time reader and I so much enjoy your creative literary style as much as the wealth of information that you provide. Through your efforts, I personally graduated from being a worried well to an informed and confident person. I did wish to ask a question, and I know that you have undoubtedly been inundated with emails (as usual) with this topic especially. I read about the discovery buy the German Oncologist back in November, that some have called a cure for AIDS. I was overwhelmed with joy to hear this extremely promising news. From what I read in all the reports (if you can believe them all) have indicated that proper scientific methods were observed throughout this process.

I understand that this does not constitute a cure; however, it does appear to be very promising.

I would love to hear your wisdom and insight into this particular issue, and I would like to understand what we know about this particular genetic resistance to HIV?

Warmest Regards, Tom

Response from Dr. Frascino

Hi Tom,

I've discussed both the delta 32 mutation (genetic mutation that leads to some degree of HIV immunity) and the recent bone marrow transplantation "cure" multiple times in this forum. Check the archives! I'll reprint below a sample of what can be found in the archives.

Happy Holidays.

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.

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

Had unprotected sex with a guy who has ccr5 delta 32 (DELTA 32) Oct 13, 2008

Last night I had unprotected sex with a guy who claims that he has ccr5 delta 32 and got a negative HIV test recently. I'm worried about it as his ex is positive. My question is do people who have ccr5 delta32 carry HIV? Is the risk of me getting HIV low? Shall I take pep or go to get a test? Thanks a lot!!

Response from Dr. Frascino

Hello,

Even if a guy strapped a lie detector on his Mr. Happy, I wouldn't believe claims that unsafe sex is not risky, because your partner states he's "delta 32." I'll reprint below some information from the archives pertaining to delta 32.

Your HIV-acquisition risk should be considered the same as that of anyone else who elected to have unprotected sex. PEP would only be recommended if your partner was confirmed to be HIV positive (or strongly suspected of being HIV positive) and if you had a significant exposure. I can't tell from your question what type of "unprotected sex" you had with Delta-Dude, but I doubt PEP would be warranted. Testing, however, at the three-month mark is warranted. I urge you to reconsider your decision to place yourself at risk for STDs, including HIV, by barebacking.

Be safe. Be well.

Dr. Bob

No HIV in 8 years (DELTA 32) Nov 1, 2007

To Whom It May Concern:

Thank you for your time in reading this. I am writing to ask a question. A good friend of mine is a homosexual male. I have personal knowledge that my friend has had receptive anal sex with over 1,500 men over the past 8 years. My friend frequents hot spots in local parks and public restrooms, and finds sexual partners on the internet. According to my friend (and I find this information credible), over 90% of his sexual encounters were unprotected and most of these men have ejaculated into his rectum. Some of the men who have ejaculated in my friends rectum are HIV positive.

Notwithstanding the fact that my friend has had unprotected sex with this many men, a recent HIV test was negative.

Having had unprotected anal sex this many times and with some known HIV-positive men, why hasnt my friend become HIV positive? Is there anyone, perhaps a research institute, who would be interested in a blood sample of my friend for further analysis? It seems like somebody would be collecting this type of data.

Thank you so much in advance for your response,

Concerned with finding a cure as fast as possible

Response from Dr. Frascino

Hello,

Thanks for your post and interest in helping to find a cure as fast as possible.

If your story about your friend is indeed accurate, he is one lucky boy. He's also a boy with significant psychological issues who is courting disaster with his self-destructive and irresponsible behavior. I'm quite amazed he found 1,350 guys (90% of 1,500) willing to have unprotected anal sex with him. Is he a closeted Republican Congressman or clueless rightwing religious zealot perchance? Oh, never mind. Is it possible he could have avoided infection, despite his activities at the hot spots? Yes, it is. Not every HIV exposure leads to HIV infection. Thankfully! Your friend might even have some genetic predisposition against HIV infection. (See below.) The bottom line, however, is that he's putting his bottom at risk with every unprotected poke he gets and sooner or later he's going to lose the STD/HIV sexual Russian roulette game big time. My advice is that you try to convince your good friend he needs help. We don't need his blood, but he definitely needs counseling and a change in behavior ASAP.

Dr. Bob

HIV+ Resistant Sep 12, 2007

Dear Bob,

Six month after he left me, My boyfriend send me a letter to tell me he had been tested positive and had developped aids. We had been together for two and a half years. We had unprotected sex many times, almost daly. He thinks he was infected throughout our relationship. I received loads from him in my mouth as much as in my ass. I got tested when I received his letter and was diagnosed negative. I got tested every year since then and still negative. It has been five years now and I have had other relationship with many partners. Is it possible that I am immune against the virus. That my body is protected against it. Is there a test we can take to see if our immune system can fight the virus on its own. If so where can I take such a test. I live near Montreal in Quebec, Canada. Thanks for your time. Cheers, Eric

Response from Dr. Frascino

Hello Eric,

Are you immune to HIV? No, most likely not. What you are is damn lucky! I urge you not to push your luck by assuming you are immune. That's playing sexual Russian roulette and ultimately you will lose.

I will reprint below some information from the archives concerning the Delta 32 mutation. This is an evolving story. Even with the mutation you would not be immune to all types of HIV.

Stay safe. Stay well.

Dr. Bob

delta 32 Mar 17, 2007

Dr. Bob ...

I think I may have heard everything now! So, I'm on Craigslist just 'poking' around and I see this guy who wants to have sex - but, he only does it bb. Now, here is where it gets wacky! He's HIV Negative and says, "I just got tested in January, but, I just do that so guys will know the right answer. I don't worry about HIV ... I'm delta 32."

What does that mean? I went to a link, that he provided, and it talked about smallpox, and the plague.

What gives? Is this guy a bit crazy or is he really "safe?"

Can you shed some light, my friend?? :)

Thanks!! Oh and P.S., I thought I found Prince Charming ... But, it wasn't him! I'm still looking! You have any cute friends in Orange County?

QS

Response from Dr. Frascino

Hey QS,

So you were poking around Craigslist looking for some poking?

Delta 32 is a bit complex to explain, but I'll give it a shot. First, some background. HIV can only infect certain cells that have specific "receptors" on their surface that allow HIV to enter. HIV attaches to CD4 receptors. However, CD4 alone isn't enough for viral entry. Another protein called CCR5 is also needed. CCR5 is called a co-receptor. Some folks have a mutation in the CCR5 gene called CCR5-delta 32 mutation. This mutation changes the configuration of the CCR5 protein such that HIV cannot bind to it. Genes, of course, are inherited. If you inherit a CCR5-delta 32 gene mutation from both parents, your chances of becoming HIV infected are dramatically reduced. This occurs in about 1-3% of Caucasians. If you inherit one CCR5-delta 32 mutation (from just one parent), it will confer some protection against acquiring HIV and may make HIV disease less severe if you do become infected. Current estimates are that 10-25% of Caucasians may have a single CCR5-delta 32 mutation.

So should Craigslist Delta-32 Boy "not worry" about HIV? Absofrickinlutely NOT! It is downright dangerous to assume you are safe if you have the CCR5-delta 32 mutation. It is not a guarantee of HIV immunity. HIV is much too smart for that. Some strains of HIV use proteins other than CCR5 as co-receptors to enter CD4 cells.

As for the bubonic plague (Black Death) and smallpox link, it appears that the CCR5-delta 32 mutation may have arisen to protect folks in Europe from these illnesses. The mutation affords protection from these ailments and could have arisen via an evolutionary process. (Yes, right-wing religious wing-nuts, evolution does indeed exist!)

So if you happen to hook up with Delta-32 Boy, you might want to give him a science lesson along with his poke.

Finally, hotties in Orange County? Sure, I know some Prince Charmings in that zip code, but unfortunately none are currently single. So I guess you'll just have to continue kissing those toads until your prince arrives.

Good luck.

Dr. Bob



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