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The Search for the Cure Heats Up! Part Three


Cure Strategies; Cure Realities

By Bob Frascino, M.D.

March 1, 2011

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As I mentioned in Part I of this three-part blog-a-thon, HIV is far more clever and cunning than any of us realized in the early days of the epidemic, when we all assumed that with the three Ts -- time, talent and treasure -- we could cure HIV in the not-too-distant future. Three decades later, despite billions of dollars and the best efforts of research scientists, HIV still has no cure and has prematurely snuffed out the lives of over 25,000,000 people.

So why don't we have a cure? At the July 1996 International AIDS Conference in Vancouver, scientific evidence was presented that definitively showed effective combination antiretroviral therapy, which included the recently developed protease inhibitors, could reduce HIV in the blood to undetectable levels. Many assumed we merely needed to administer ART for a period of time, perhaps three to five years, in order for the virus to burn itself out and thus for HIVers to be cured. Unfortunately that was not reality, because each time ART was stopped, the virus came roaring back, no matter how long the individual remained undetectable before interrupting ART.

The reason for the resurgence when ART was no longer on board is the same reason curing HIV has been so incredibly challenging: viral reservoirs. So what the heck are they? Let me try to explain. Viruses, such as HIV, are not self-sufficient organisms, like certain bacteria, parasites or other germy illness-causing invaders. A virus is, in essence, just a small package containing a tiny strand of genetic material called DNA. This DNA contains the genetic code for the virus itself. For HIV to cause infection it must find a host (like me, for instance), enter the host's cells (such as my immune system CD4 T cells), and deliver its DNA payload directly into the genetic core (the nucleus) of the host cell, which is where the host DNA is stored. OK so far? Good. Let's proceed.

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DNA is basically a long-chain chemical code that carries the genetic information that allows an organism to operate. It basically instructs the body's machinery, advising it to make proteins and other elements the organism needs to survive and thrive. Each of the trillions of cells in a human body contains a complete copy of its unique DNA. Cool eh? Most cells only use a small portion of the DNA strand. A human DNA strand is nearly six feet long when stretched out. That's several inches taller than me!

And so what does this have to do with HIV reservoirs? Glad you asked! HIV is an unusual virus, because it contains an enzyme (protein) called integrase. Integrase astonishingly "integrates" the small thread of viral DNA directly into the host DNA. Yeah I know, it sounds very sci-fi, doesn't it? The viral DNA then maliciously hijacks a small piece of the host cell's machinery and turns it into a crazed viral Xerox machine. The infected cell begins cranking out new HIV particles with amazing speed and efficiency. Each replication travels through the bloodstream in search of new cells to infect, transforming them into new manic viral copy machines. Frightening, eh?

So what about antiretrovirals? Effective combination ART can shut the copy machines off, halting the mass replication of the virus. But they unfortunately cannot excise the viral DNA from the host cell. The cell remains infected. Some viruses, even nasty ones like hepatitis C, can be eradicated ("cured") if viral replication is effectively turned off for a long enough period of time. But not HIV! As you may have guessed by now, HIV cunningly infects certain cells of the immune system, which are very, very long-lived. These are a subset of so-called memory cells. These memory cells help the body respond quickly to infections it has experienced in the past. It's a nifty immune mechanism, but a small portion of these remarkable memory cells (maybe only one in a million) become dormant sleeper cells. These can remain "asleep" and quiescent for decades. The dormant memory cells that are infected with HIV constitute the "latent HIV reservoir."

When these infected sleeper cells are awakened by a stimulus or immune challenge, they, too, become crazy HIV replication machines, spitting out new infectious HIV particles. Sure, if ART is on board, it can shut off viral replication and the awakened cell will eventually die. But due to the long life of some of these dormant sleeper memory cells, HIVers must stay on ART for decades and decades, essentially a lifetime. This is the crux of why a cure for HIV has been so elusive.

Of course those frustrated with the slow scientific pace toward curing HIV could turn to only one of the dozens of instant HIV cures (for a hefty fee) that are readily available on the Internet. There are a wide variety to choose from. These bogus products claim to immediately cure HIV with a zap of electricity, whiff of ozone or secret mixture of herbs. (See my blog on this topic: "Hocus-Pocus: Quantum Quackery, aka Alternative Medicines for HIV/AIDS, A View From the Reality-Based Universe"). By the way, these same products also cure cancer, diabetes, hemorrhoids, halitosis and the heartbreak of psoriasis. So you really get quite a bang for your buck.

Returning to a reality-based universe, although we still can't eradicate HIV, we are indeed closing in on a cure from several different paths. The simplest and most direct strategy for eradicating the virus involves administering a treatment to the HIVer that would wake up all the infected cells in the latent HIV reservoir so that they would start producing virus. ART would shut down viral replication, and the cell would eventually die, as it would no longer be dormant (asleep). This proposed scenario was attempted most notably with interleukin-2 and with valproic acid.

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See Also
The Search for the Cure Heats Up! Part One
The Search for the Cure Heats Up! Part Two
Eliminating HIV/AIDS: How We'll Get to Zero
Can HIV Infection Be Cured?
More Research on a Cure for HIV/AIDS
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Reader Comments:

Comment by: Carles (Barcelona) Wed., Jun. 1, 2011 at 6:38 am EDT
You begin your article saying "HIV is more clever..." I guess that you are wrong, HIV is a dumb son of bitch who no one can understand due to it's stupidity and so no one finds how to kill it.
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Comment by: Marc (beirut-lebanon) Sun., Apr. 17, 2011 at 7:33 am EDT
Another functional cure on the horizon, lets hope it will be here soon.

Budapest, Hungary (SERIOUS SPECULATOR – 4/11/11) Genetic Immunity, a US/Hungarian biotech company today announced significant results in its Phase II testing of its flagship product, DermaVir, the world’s first dendritic cell-targeting HIV vaccine candidate, that offers the potential of a “functional cure” for HIV/AIDS infected patients.
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Comment by: David (Iowa City, IA) Wed., Apr. 20, 2011 at 8:29 pm EDT
This is a great news! I never heard the related news before. Do you have more detailed information for the result and research. I hope a cure for HIV coming as soon as possible!


Comment by: J (S.C.) Thu., Mar. 31, 2011 at 6:06 pm EDT
I pray that a cure for HIV will be found soon living with this disease has cost me my career, I don't want to have to be on drugs for the rest of my life and having to deal with knowing I can do more things in life if only I didn't have this disease to worry about, My prayers go out to the scientist that are working diligently on getting a cure out there for everyone living with this illness, I just pray that a break through a real serious breakthrough will be found soon so myself and others will be able to live a normal well healthy life again. I know that God is merciful and gives second chances I pray that we all will get that second chance to live happy again and not have to deal with this illness. Thanks again to all the researchers, scientists, and doctors that are doing all they can to end this epidemic.
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Comment by: Lorena (Macomb, IL) Wed., Apr. 6, 2011 at 11:21 pm EDT
God helps those who help themselves. What can we do to help a cure materialize?


Comment by: Pierre (AD) Fri., Mar. 25, 2011 at 5:39 am EDT
What Do you Think about Abzymes? Studies done in animals proved abzymes to be effective against HIV.
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Comment by: stanley chelang'a (taveta ,kenya) Thu., Mar. 24, 2011 at 3:08 pm EDT
hi all.i am an HIV cordinator in a Taveta sub county.recently there has been an event which brings hope and wonderment. there is a retired priest who gives people boiled herbs. HIV clients i know have stopped taking ARV's after takjing the herb.
i am in the crossroad trying to advice them against stopping
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Comment by: nick mark (atlanta, GA) Thu., Mar. 24, 2011 at 11:33 am EDT
What an insightful article! Thank you Dr for allowing us to peer through the effort that's been undertaken by heroes like you around the world. I sure hope we get a cure for this nasty disease SOON keep up the great work and effort. Thank you
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Comment by: Mac (New York) Wed., Mar. 23, 2011 at 8:18 pm EDT
HIV cannot kill our hope and our faith. There will be a cure. There were times when a cure for syphilis or TB was unthinkable. Think of what a diagnosis of HIV was in the 80s and what it is now. The medications work, they keep getting better, HIVers are living longer and healthier lives. Let's not give in to despair and to the nay sayers. Lots of new treatments in the pipeline. Many good things to come. Live well, stay strong, keep up the faith. And love.
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Comment by: Anonymous Fri., Mar. 18, 2011 at 10:26 am EDT
Many Thanks Dr. Bob - one of the most concise and lay-understandable summaries I have read on the subject!
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Comment by: Kary Frank (New Delhi) Fri., Mar. 18, 2011 at 2:29 am EDT
Really good news, millions of people are awaiting for this, great and keep it up, hope the day (cure of HIV) is very near….
Thank you Dr Bob
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Comment by: Arthur G. (Bella Vista, AR) Thu., Mar. 17, 2011 at 3:52 pm EDT
In study in France it took only a small amount to virus to have the disease bounce back, so it is not likely there will be any functional cure. All the virus will have to be removed. Of cause some people that do not advance to AIDS.

The other problem is that Haart only works for a certain amount of time. As the patient will premature age. I noted that you can have normal CBC counts but endup with cancer. We don't have a tissue test to see damage done there. Sure enough we are seeing diabetes, heart disease and cancer in HIV people in there 50's and 60's.

I would not hold breath on drug companies putting themselves out of business. Nor do I think our government research is going to make much progress as these people other job option is working for the drug companies. Besides we believe in the capitalist system will solve anything as long as we throw enough money at it. If only the virus bug would follow our bias. I look forward to curing cancer in the year 3,000!
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Comment by: Paul (Dayton, OH) Wed., Mar. 23, 2011 at 2:44 pm EDT
This comment illustrates everything that is wrong with the poz community's relationship with the idea of curing HIV. "The drugs we have will kill us, and if they don't the lingering effects of the virus will finish us off early. It'd be nice if there was a cure, but no one is going to put themself out of business. Sucks to be us." Obviously all of that is true, but its stated more to terminate hope than frame the scope of the problem. So what we need to do is MAKE SOMEONE FIND A CURE. You're right, the drug companies don't want to find a cure, and the government couldn't care less. So scream. Protest, donate, demand, support...do EVERYTHING you can to find a cure. Becuase you're right Arthur, there is no political or economic mechanism which will automatically lead to a cure. Let's make one.


Comment by: Dr Andre Hill ( Montego BayJamaica) Thu., Mar. 17, 2011 at 2:15 pm EDT
This is all very interesting!!!

And I do hope that a cure is just around the corner.What a thing that would be.Indeed HIV seems to be running out of time.Keep up the good work.

Best regards
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Comment by: Greg R. (Corydon,In.) Thu., Mar. 17, 2011 at 1:30 pm EDT
Hello Dr. Bob, thank you once again for bringing 'clarity' to subject matter.I can not begin to tell you how you have made my day by stepping up and giving your interpretation and evaluation of this promising news.After taking meds for 22 years now I am so looking forward to 'The Cure"---Surely this time we all won't be getting our hopes up only to be disappointed later on down the line.---Hangin in there....Greg
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Comment by: River Sun., Mar. 13, 2011 at 4:26 pm EDT
It all sounds very promising and we certainly know a lot more about HIV than 10 years ago. The research seems to be focusing on very specific aspects of the HIV behavior and the Berlin patient actually shows that technically a cure is possible.
We HIVers just need to stay strong and continue our fight. I'm very healthy without any therapy and this also is probably affecting my optimism but I personally feel I became a much better person since I found out (5 years ago). I'm a lot wiser and a better friend, son and brother then I used to. Life challenges such as HIV either kill you or make you stronger (and I don't mean physically). I agree that if a cure will be found it will not erase stigma and fear. Unfortunately such issues won't be healed with a vaccine or a therapy. If one day we'll be cured let's not forget what it means to feel different, what it means to feel and be excluded and let's teach and help future generation to act differently.
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Comment by: Roland (Columbus, OH) Mon., Mar. 14, 2011 at 7:09 pm EDT
So true about the last sentence. So true. Thank you for sharing.


Comment by: patrick (boston) Sat., Mar. 12, 2011 at 5:35 am EST
a functional cure would not work since it won't erase the stigma, those scarlet letters....HIV. and total eradication of the virus and truly cure hiv patients because not only will it cure the hate and the ignorance, but it will give them peace of mind to know that they can now wake up and not be judged anymore. furthermore, a functional cure will only delay the search for a true cure because of the mentality of "it's good enough" and so the research will plateau again.
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Comment by: Roland (Columbus, OH) Sat., Mar. 12, 2011 at 5:29 pm EST
Well, we're getting into some cerebral stuff here Patrick. You're rightfully concerned about whether or not a "functional cure" would address the stigma. The short answer is that if we can't infect anyone, if we don't require further treatment and we don't progress, does anyone really need to know whether or not we have the disease? At some point, the stigma could become as irrellevant as we choose to make it. Your final sentence belies an immensity of wisdom which may answer this question. "Research will plateau again". The only reason we'd be concerned about that is because there might be a need for further research. I think a lot of us who favor an actual cure are on the same page with this concern. The phrase "functional cure" would quickly be replaced by "treatment". This disease f**ks us up. Every single time we think we've made progress against it, we find out some new way that it f**ks us up. People talk of having relationships with their HIV. They compare it to a pet, and go on about how they hold long conversations with it. This isn't a cat, its a monster. I want every pozzie to understand this: Your HIV is not a cold. Its not a parasite. Its not a companion. It wants you to die. It wants to precede your death with profound misery. There can be no cohabitation with this thing. It doesn't want to "snack on our T cells". It will move on and cause damage to anything it can. Already, researchers hypothesize that it infects other cells, like brain cells. Its not "just a virus". It wants to f**king kill us all. Employ whatever conspiracy theory you want to explain this, but understand this, HIV is not going to stop, be contained, or shut up. Eradication is the only answer. Anything short of that is just providing it with another openeing to f**k us up further down the road. Save cohabitation for your roomate. HIV needs to be thrown out at almost any cost.
Comment by: Eugene (Moscow, Russia) Tue., Mar. 15, 2011 at 5:18 pm EDT
No doubt you are right about the point of delaying in searching the cure in a miracle case if the functional one is currently on board, but for decades we still have nothing just a poison that takes our life quality for the one and, in general, a whole lives for the others in order to make their lives just longer till no one knows. So let it just be. Even like a sign of hope for the first relief. I would be appreciate to have good news related some "new Berlin patients". Then millions will follow...
Comment by: ethan w. (nashville, tn.) Thu., Mar. 17, 2011 at 10:35 am EDT
Bravo, Roland!!! I could not agree more with you. This is exactly how i feel as well. We've become so comfortable with hiv, and for what reason? Why? There is nothing "cute" about this virus. And we shouldn't put out the message that it can be "cute" to live with it. We desperately need a cure because it has killed millions, will continue to kill millions and has ruined lives. What are we going to do about this? We need to be more serious about this.
Comment by: Sven (Norway) Sun., Mar. 20, 2011 at 8:25 am EDT
Roland you have stated the truth very powerfully. I shrink with disbelief when I read that someone with HIV has written about "My Beautiful HIV" or "HIV: My Wonderful Companion". It is indeed total nonsense. Only by facing the reality that HIV is a monstrous disease will all of us, together, finally overcome it. Thank goodness there are so many scientists who are NOT going around talking about HIV as if it were a fabulous friend. They KNOW how pernicious it is, and only by acknowledging its true nature will they inch towards a cure.
Comment by: River (Italy) Thu., Mar. 24, 2011 at 6:11 pm EDT
I agree with Roland but only to a certain extent. Of course HIV is the enemy and our final goal is and always will be defeating it. Other incurable diseases have taken a lot of time before a cure was finally found. In the meantime I do think it's right to embrace your status and make the best out this challenge. We don't know when and if a final cure would be found and we can't just spend our days hoping and praying and acting as victims. I am part of this society, I work, I have a career and I haven't given up any of my dreams. I don't know if I will be cured one day but in the meantime I still want and deserve a freaking good and satisfying life!


Comment by: ethanwilson (nashville, tn.) Thu., Mar. 10, 2011 at 3:52 am EST
Thank you for the information. I am positive and really concerned, as is ALL people infected. Please continue to give us information on an hiv cure. I just wish that more people believed in it. So many people i have talked to believe in the conspiracy theories, ex: pharmacies making millions off the drugs. I wish that people weren't so cynical. How will we ever make progress if we stay in this mindset. Please continue to let the readers know about the lastest information. Thanks again.
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Comment by: michael (los angeles) Sat., Mar. 12, 2011 at 5:27 am EST
there is good reason....why would you patent a life saving drug? what good would it do to hiv patients if medicines like truvada is patented for ten years, preventing it from being made cheaply and available to those who need it? so instead of being able to afford the medicine, it will cost 1000 dollars....if the government wants to help, it will partner with organizations to buy the patents to these medicines off these bastards hands and distribute it to those who need them at a cheaper price...but guess who makes the laws and who stuffs their pockets? lobbyists in congress.
Comment by: Sacha (Paris (France)) Sun., Mar. 20, 2011 at 8:19 am EDT
Remember that the good guys nearly always win. Adolf Hitler did not succeed in gaining control of all of Europe and then the rest of the world. Gaddafi is not going to succeed in his quest to hold onto Libya. Humankind has conquered so many of the world's terrible diseases. There are hundreds of scientists and organizations on earth who really seek the prize of beating HIV. Whoever finds the cure will be "immortal" in human memory for all eternity.


Comment by: Anonymous Mon., Mar. 7, 2011 at 1:35 pm EST
How can somebody donate to the reseach going on? Here in the UK it's easy to donate to THT and other organisations that support people living with HIV (extremely worthwhile) but is there an equivelent of the cancer research trust?
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Comment by: mario (barcelona) Sun., Mar. 6, 2011 at 11:05 am EST
I remember Dr.Bob in his posts always being critical towards reaching a cure in our lifetime. It really makes me hopeful reading that from him now. Something must have dramatically changed.
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Comment by: Jay ( S.C.) Thu., Mar. 31, 2011 at 6:24 pm EDT
Well if he was against a cure and now is on board then the cure must really be on the horizon, people usually don't just change their stance on something like that, unless something really opened their eyes to see that change is truly coming.
Comment by: farai (australia) Fri., Apr. 8, 2011 at 8:41 pm EDT
I think it just confirms the confusion surrounding the subject, even among our so-called experts and worse among us sufferers.


Comment by: Tim ( Sydney Australia) Sun., Mar. 6, 2011 at 8:20 am EST
You give firm and informative information Dr Bob and more importantly hope! ThankYou x
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Comment by: Anonymous Wed., Mar. 2, 2011 at 1:24 pm EST
I was wondering where you would feel donations would have the greatest impact: Cure or Service Orginizations?
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Comment by: emily (London UK) Wed., Mar. 2, 2011 at 9:09 am EST
I hope they CURE HIV or at least have a functional cure soon! I hope science and medical people are working hard to CURE this!

Thanks Dr bob you give me hope that a cure for HIV will happen soon.
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Comment by: Szelenski (Chicago, IL) Tue., Mar. 1, 2011 at 12:58 pm EST
Looks very promising.I was able to understand ( you see I am ignorant about the medical technicality. I am basically who screw the silicon chips and get some software done to screw some jobs what they called automation ). Why the hell, human race is in race fighting each other for supremacy forgetting the co-existing biological killers. First the plague,TB,malaria alright I agree, they had find the cure! but after how long after? Had been more creative and tactical in research, than in wars, we would have said cheers for the beer on Moon many decades back!!!!
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Bob Frascino, M.D., was President and Founder of The Robert James Frascino AIDS Foundation. He had been an outspoken, popular expert in TheBody.com's "Ask the Experts" forums on safe sex and fatigue/anemia since 2000. Once a Fellow of the American Academy of Allergy, Asthma, and Immunology, and the American Academy of Pediatrics, Dr. Frascino served as Associate Clinical Professor of Medicine, Division of Immunology, Rheumatology, and Allergy, at Stanford University Medical Center from 1983 until 2001. He was a member of the American Academy of HIV Medicine and had also been a distinguished member of the executive boards of numerous state and regional associations.

We're inexpressibly saddened to share the news that Dr. Frascino passed away unexpectedly on Saturday, Sept. 17, 2011. Click here to read more and to share your thoughts.


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