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Author Topic: Closing in on an Aids vaccine  (Read 3104 times)

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Offline Boze

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Closing in on an Aids vaccine
« on: May 22, 2010, 07:39:44 AM »
http://www.guardian.co.uk/society/sarah-boseley-global-health/2010/may/18/hiv-infection-vaccines

Closing in on an Aids vaccine
Seth Berkley, president, CEO and founder of IAVI, the Aids vaccine initiative, explains in a guest blog how these are exciting times for scientists engaged in one of the most important quests of our age.



Today is World AIDS Vaccine Day. It marks the day, 13 years ago, when U.S. President Bill Clinton challenged the world to develop an AIDS vaccine within a decade.

The timeframe may in hindsight seem overly optimistic but most of us could not have conceived how difficult the task would prove to be. We found out soon enough. A year after Clinton's speech, the first large-scale AIDS vaccine study was launched, and the experimental vaccine failed to show efficacy.  So did the second AIDS vaccine candidate targeting a different arm of the immune system and thought to be promising and tested in an efficacy trial. By late 2008, many of the champions of the global AIDS vaccine effort had gone from being cautiously optimistic to grimly determined?what alternative was there? No number of failures can change the fact that vaccines hold the greatest promise for ending the AIDS pandemic.
Then came RV144.

A joint project of the US and Thai governments, this study in Thailand evaluating a two-step regimen of two different AIDS vaccine candidates came up positive late last year. This is not to say that we now have a vaccine ready for market. The regimen provided about 30% protection from HIV, not enough to satisfy public health authorities. What it has given us, however, is the first demonstration that a vaccine can indeed protect humans from HIV infection. That affirmation sent ripples of excitement radiating out across a field in need of a morale-booster.

Because the Thai trial results were a surprise?many researchers had predicted no protective effect against HIV infection--there is renewed interest in the efficacy testing of other existing or newly modified experimental AIDS vaccines. The RV144 results illustrate that HIV vaccine candidates with sound hypotheses must be evaluated in humans before conclusions can be drawn about their effectiveness. After all, earlier studies (including with individual vaccine components) had suggested that the RV144 regimen did not hold much promise.

At the same time, the HIV vaccine field could do with some new approaches. New approaches are coming. Those targeting the cellular immunity arm of the immune system look far better than the first generation candidates in the best of the animal models; these will be going into human trials in the next few years.  However, even more important, is the quest to design vaccines that harness the antibody response, a vital aspect of vaccine-induced immunity that has long been stymied by the extreme mutability of HIV: every time the body figures out how to target and neutralize HIV, it simply changes it structure to evade the antibody response. But a subset of antibodies, known as broadly neutralizing antibodies (bNAbs), which are capable of preventing a wide range of HIV variants from infecting cells, hold clues to the design of potentially powerful HIV vaccines. Until recently, only four antibodies widely regarded as broadly neutralizing had been isolated from HIV-positive individuals in the developed world and these were relatively weak.

That, too, changed last year when researchers at and affiliated with the International AIDS Vaccine Initiative discovered two new and highly potent ones from a volunteer in Africa as well as the site on HIV to which they attach. This site provides researchers with a promising model to use to design a vaccine against AIDS. Since then, still more bNAbs have been discovered by researchers affiliated with IAVI and the U.S. National Institutes of Health?and more are coming each month.  In combination, these antibodies neutralize virtually all strains.

With these discoveries, HIV vaccine researchers are gearing up for an exciting decade. Of course, considerable work remains to be done to convert these discoveries into vaccines that can be widely used, and resources must be mobilized to fund it. The feasibility of financing mechanisms for the development of new health tools and technologies to combat the diseases of poverty are being discussed this week at the World Health Assembly in Geneva.  Such mechanisms are needed to help ensure that investments in the health of vulnerable populations are not subject to the vicissitudes of the market or the sour politics of economic downturns. However, we now see that investments in HIV vaccine development are paying off (including long term support from the UK DFID), as illustrated by the scientific advances of recent months. This hard-won momentum must be sustained.

If we do not sustain it, we may never rid the world of the unspeakable misery of AIDS.
==========
Aug08 - Seroconversion
Mar10 - Diagnosis; cd4 690 - VL 19,000
Apr10 - cd4 600
May10 - VL 4,500
Jun10 - started Atripla ; VL 113
Jul 10 - UD vl, CD4 590
Aug 10 - UD, CD4 810, 52%
Nov 10 - UD, CD4 980

Offline Hellraiser

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Re: Closing in on an Aids vaccine
« Reply #1 on: May 22, 2010, 10:32:32 AM »
I appreciate your interest in a vaccine, but you better hope that if a vaccine is found it has massive therapeutic value for those of us who are already infected, because if they find a way to stop the infection from spreading I have no doubt in my mind that the remaining interest in us will be long gone.

Offline Boze

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Re: Closing in on an Aids vaccine
« Reply #2 on: May 22, 2010, 11:11:44 AM »
Hellraiser,

I don't think so. Today HIV / AIDS cost is about $55 Bn a year, 5 of which is on research. The rest is on 'us'. It's a very expensive disease for societies.
==========
Aug08 - Seroconversion
Mar10 - Diagnosis; cd4 690 - VL 19,000
Apr10 - cd4 600
May10 - VL 4,500
Jun10 - started Atripla ; VL 113
Jul 10 - UD vl, CD4 590
Aug 10 - UD, CD4 810, 52%
Nov 10 - UD, CD4 980

Offline Hellraiser

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  • Semi-misanthropic
Re: Closing in on an Aids vaccine
« Reply #3 on: May 22, 2010, 11:22:47 AM »
Hellraiser,

I don't think so. Today HIV / AIDS cost is about $55 Bn a year, 5 of which is on research. The rest is on 'us'. It's a very expensive disease for societies.

You mean it is a veritable cash cow for pharmaceutical companies.

Offline Boze

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  • Posts: 477
Re: Closing in on an Aids vaccine
« Reply #4 on: May 22, 2010, 11:43:22 AM »
no,

1) Pharmaceutical companies only get about $12bn a year now
2) That is still a large number - that is paid by governments / insurance co. So they are just as interested  in finding a solution (as you imply pharma is interested in keeping the cash cow going).
Who footed the $100mio bill for the Thai vaccine trial - US military. 
==========
Aug08 - Seroconversion
Mar10 - Diagnosis; cd4 690 - VL 19,000
Apr10 - cd4 600
May10 - VL 4,500
Jun10 - started Atripla ; VL 113
Jul 10 - UD vl, CD4 590
Aug 10 - UD, CD4 810, 52%
Nov 10 - UD, CD4 980

Offline jcelvis

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Re: Closing in on an Aids vaccine
« Reply #5 on: May 23, 2010, 01:02:08 AM »
I appreciate your interest in a vaccine, but you better hope that if a vaccine is found it has massive therapeutic value for those of us who are already infected, because if they find a way to stop the infection from spreading I have no doubt in my mind that the remaining interest in us will be long gone.


Such a pessimistic outlook, and not very likely at all just look at history. We found a way to treat syphilis, we have vaccines for Hep A and Hep B, and all of those diseases are still with us and still being researched. Heck a vaccine just came out for HPV and parents refuse to get their kids vaccinated because they don't want to talk to them about sex.

I believe is a vaccine is found it will be much like Hep A and Hep B, targeted to high risks groups, and only to adults. That will drastically lower the rate of infection, but it wont mean there are no new infections.

There 34K new cases of Hep B alone in the United States each year for a disease which can be prevent through vaccination. The vaccine for Hep A was approved in 1995, and infection rate has dropped 89% from the 1995, but it's still not 100%.

Change the way you view the world, and the world around you changes.

Offline WhySoUnfair

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Re: Closing in on an Aids vaccine
« Reply #6 on: May 23, 2010, 01:57:07 AM »

Such a pessimistic outlook, and not very likely at all just look at history. We found a way to treat syphilis, we have vaccines for Hep A and Hep B, and all of those diseases are still with us and still being researched. Heck a vaccine just came out for HPV and parents refuse to get their kids vaccinated because they don't want to talk to them about sex.


how long did it take for us to find a cure for syphilis? I think it's a few hundred years!  I often wonder whether our current HIV meds will become resistant like antibiotics do. While the priest climbs a post, the devil climbs ten -- HIV virus mutates too fast.

Offline leatherman

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Re: Closing in on an Aids vaccine
« Reply #7 on: May 23, 2010, 02:09:42 AM »
I often wonder whether our current HIV meds will become resistant like antibiotics do. .... HIV virus mutates too fast.
HIV is not some wildly mutating strain of virus.

Resistance happens when people do not keep the proper level of medication in their system. When the amount of meds in a patient's system drops below the proper threshold, hiv is able to mutate (it learns to overcome the weakened drug), become resistant to the med, and the med is no longer effective against the mutated strain of virus.

Many people have been on the same meds for 10 to even 15 years with no resistance issues whatsoever.

Sometimes med switches are often made for reasons other than resistance. Sometimes meds are switched to overcome a side effect; sometimes for ease of dosing; and sometimes for cost benefits.

I just recently switched off one med that I've been taking for 15 years. Not because of side effects or because I had allowed the med to become resistant to it; but because it cut down the number of pills I took each day, it simplified my regimen to taking pills at only one time each dinner, and it cost nearly $300 less.
leatherman (aka mIkIE)


chart from 1992-2013; updated 2/09/13  Reyataz/Norvir/Truvada

Offline tednlou2

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Re: Closing in on an Aids vaccine
« Reply #8 on: May 23, 2010, 03:04:34 AM »
I can see what Trey is saying.  If a vaccine came out tomorrow and most people got vaccinated, I think there would be a fear in those of us already infected that there was no longer a need to seek a cure for us.  I think the fear would be that researchers would now say it can be prevented and those already infected could live the rest of their lives on current meds.

Also, I think the interest in an HIV vaccine would be much different than Hep B or HPV.  I think many don't feel the same fear of those as they do HIV.  I know, we are all infected so we must not have felt that fear to HIV.  I can see where many would think they aren't at risk, so why get the vaccine.  Or, there would be fear of this new vaccine for years.  I'm sure FOX News would spread fear that it could cause AIDS.  So, I could see where there would still be many infections even with the vaccine for years.

I would think with an amazing new HIV vaccine, there would be a huge campaign to get people vaccinated.  The gov't may even make the case that it should be mandatory due to the huge cost of all the HIV cases and effects on national security. 

Offline jcelvis

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Re: Closing in on an Aids vaccine
« Reply #9 on: May 23, 2010, 02:59:31 PM »
I can see what Trey is saying.  If a vaccine came out tomorrow and most people got vaccinated, I think there would be a fear in those of us already infected that there was no longer a need to seek a cure for us.  I think the fear would be that researchers would now say it can be prevented and those already infected could live the rest of their lives on current meds.

Also, I think the interest in an HIV vaccine would be much different than Hep B or HPV.  I think many don't feel the same fear of those as they do HIV.  I know, we are all infected so we must not have felt that fear to HIV.  I can see where many would think they aren't at risk, so why get the vaccine.  Or, there would be fear of this new vaccine for years.  I'm sure FOX News would spread fear that it could cause AIDS.  So, I could see where there would still be many infections even with the vaccine for years.

I would think with an amazing new HIV vaccine, there would be a huge campaign to get people vaccinated.  The gov't may even make the case that it should be mandatory due to the huge cost of all the HIV cases and effects on national security. 

First off you need to stop fallacy of just because it's important to me it's important to everyone else. Large groups of people are not concerned with HIV infection. It makes it more difficult to vaccinate people who don't believe they are at risk. It's much easier to contract Heb B,  and we still don't vaccinate everyone in the United state. 350 million people are infected with  chronic Hep B, and only 50 million infected with hiv.

Only one disease has been eradicated and that's smallpox. Polio vaccine was discovered in the 1950, it wasn't until 1988 that they attempted global eradication, and we are now in 2010 and it still has about 1000 cases a year. Even if a vaccine was found you'd ability to co-ordinate a global eradication plan would take years if not decades. In the meantime more people would still be infected with the disease.

Change the way you view the world, and the world around you changes.

Offline sam66

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Re: Closing in on an Aids vaccine
« Reply #10 on: May 24, 2010, 03:16:34 PM »
Leatherman,

   
HIV is not some wildly mutating strain of virus.

            Is this 100% correct leatherman, I seem to recall reading HIV was a fast mutating virus.

    " HIV-1, even within subtypes, has a high rate of variation or mutation. In drug treatment programs, virus mutation can result in virus escape rendering drug therapy ineffective."

      http://www.geovax.com/technologyandproducts/hiv.php
december 2007 diagnosed +ve ,

Offline leatherman

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Re: Closing in on an Aids vaccine
« Reply #11 on: May 24, 2010, 04:13:41 PM »
Is this 100% correct leatherman, I seem to recall reading HIV was a fast mutating virus.

"HIV-1, even within subtypes, has a high rate of variation or mutation. In drug treatment programs, virus mutation can result in virus escape rendering drug therapy ineffective."
you needed to continue reading in that passage to understand what I was saying to a scared newly-diagnosed person who, in searching the net and finding false, out-dated information, believes that today's meds are not effective enough and that his life is in jeopardy.

Quote
HIV-1, even within subtypes, has a high rate of variation or mutation. In drug treatment programs, virus mutation can result in virus escape rendering drug therapy ineffective. Hence, multi-drug therapy is very important. If several drugs are active against virus replication, the virus must undergo multiple simultaneous mutations to escape. An action which is very unlikely. The same is true for immune responses. HIV-1 can escape simple immune responses. However, if an immune response is directed against multiple targets (epitopes), virus escape is much less frequent. Vaccination against more that one of the proteins found in HIV-1 virus maximizes the number of targets for the immune response and increases the chance HIV will not escape the vaccine-stimulated immune response, thus resulting in protection against clinical AIDS
HIV is fast-mutating against mono-therapy, and that's why no one uses mono-therapy any longer against HIV (this isn't the 1990s) as it was ineffective and allowed the virus to mutate. However current treatments, HAART, use an array of meds to attack the virus, giving it virtually no chance to mutate. Currently there is no maximum amount of years HAART reigmens can be taken before they are ineffective against HIV.

So for all intents and purposes HIV is NOT able to be fast mutating against today's medications. Theoretically (because it was only approved a few years ago and no one has lived long enough staying adherent) a person could start today on Atripla and continue using Atripla till their death of old age with no mutation/resistance issues. Although, it is possible for the reservoirs of HIV in a person with an undetectable viral load to mutate, most of these mutations actually make the virus less-viable and unable to reproduce progeny that would be able to thwart someone's HIV regimen.

as an example about a decade ago my HIV strain mutated causing Epivir to be ineffective. The drug Emtriva is also non-effective when that mutation is present. However, that mutation causes the HIV to be "defective" and unable to reproduce itself. After nearly 10 yrs of meds, and approx 6 years at undetectable, my mutant strain of HIV has for all intents died out and I am now able to use Truvada (which contains Emtriva) and have the drug be effective once again against the HIV in my system.

So today, I would not explain to someone that HIV was a fast mutating virus per se. If HIV was fast-mutating against HAART, we would have all been doomed a decade ago.
leatherman (aka mIkIE)


chart from 1992-2013; updated 2/09/13  Reyataz/Norvir/Truvada

Offline stargate12

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Re: Closing in on an Aids vaccine
« Reply #12 on: May 25, 2010, 01:46:14 AM »

. However, that mutation causes the HIV to be "defective" and unable to reproduce itself. After nearly 10 yrs of meds, and approx 6 years at undetectable, my mutant strain of HIV has for all intents died out and I am now able to use Truvada (which contains Emtriva) and have the drug be effective once again against the HIV in my system.

So today, I would not explain to someone that HIV was a fast mutating virus per se. If HIV was fast-mutating against HAART, we would have all been doomed a decade ago.

Very strange indeed how it was possible for your defective hiv virus to remain inside your body for so long time without entering latent reservoir  sanctuary, that should last forever ?  

Offline tednlou2

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Re: Closing in on an Aids vaccine
« Reply #13 on: May 25, 2010, 03:12:51 AM »
First off you need to stop fallacy of just because it's important to me it's important to everyone else. Large groups of people are not concerned with HIV infection. It makes it more difficult to vaccinate people who don't believe they are at risk. It's much easier to contract Heb B,  and we still don't vaccinate everyone in the United state. 350 million people are infected with  chronic Hep B, and only 50 million infected with hiv.

Only one disease has been eradicated and that's smallpox. Polio vaccine was discovered in the 1950, it wasn't until 1988 that they attempted global eradication, and we are now in 2010 and it still has about 1000 cases a year. Even if a vaccine was found you'd ability to co-ordinate a global eradication plan would take years if not decades. In the meantime more people would still be infected with the disease.



I think I agreed it would probably take years to get people vaccinated due to fears or the thinking they aren't at risk.  I thought someone told me Hep B is now part of a child's vaccination program.  Is that not true?  I could be mistaken. 

As I said, I could invision where the gov't could make it mandatory.  I read all the time that governments aren't going to be able to keep up with the growing infections and the cost and the effect to national security.  If this happened, we would see infection rates drop dramatically. 

Offline tednlou2

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Re: Closing in on an Aids vaccine
« Reply #14 on: May 25, 2010, 03:21:27 AM »
you needed to continue reading in that passage to understand what I was saying to a scared newly-diagnosed person who, in searching the net and finding false, out-dated information, believes that today's meds are not effective enough and that his life is in jeopardy.
HIV is fast-mutating against mono-therapy, and that's why no one uses mono-therapy any longer against HIV (this isn't the 1990s) as it was ineffective and allowed the virus to mutate. However current treatments, HAART, use an array of meds to attack the virus, giving it virtually no chance to mutate. Currently there is no maximum amount of years HAART reigmens can be taken before they are ineffective against HIV.

So for all intents and purposes HIV is NOT able to be fast mutating against today's medications. Theoretically (because it was only approved a few years ago and no one has lived long enough staying adherent) a person could start today on Atripla and continue using Atripla till their death of old age with no mutation/resistance issues. Although, it is possible for the reservoirs of HIV in a person with an undetectable viral load to mutate, most of these mutations actually make the virus less-viable and unable to reproduce progeny that would be able to thwart someone's HIV regimen.

as an example about a decade ago my HIV strain mutated causing Epivir to be ineffective. The drug Emtriva is also non-effective when that mutation is present. However, that mutation causes the HIV to be "defective" and unable to reproduce itself. After nearly 10 yrs of meds, and approx 6 years at undetectable, my mutant strain of HIV has for all intents died out and I am now able to use Truvada (which contains Emtriva) and have the drug be effective once again against the HIV in my system.

So today, I would not explain to someone that HIV was a fast mutating virus per se. If HIV was fast-mutating against HAART, we would have all been doomed a decade ago.

Mikey,

You'll remember I talked about the hospital putting me on mono therapy--they only gave me the Sustiva portion.  I'm now resistant to that and can't take Atripla or Nevarpine or whatever the spelling is.  I've read a lot about how mutations can actually be good and make HIV less fit at the cost of losing a med. 

Do you have any idea whether I may have actually gain some benefit by making my virus less fit at the cost of losing that med?  Or, have I read the information incorrectly.  I have that K103N mutation 

Offline leatherman

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Re: Closing in on an Aids vaccine
« Reply #15 on: May 25, 2010, 07:26:54 AM »
Very strange indeed how it was possible for your defective hiv virus to remain inside your body for so long time without entering latent reservoir  sanctuary, that should last forever ?  
because it's a defective mutation. kinda the "law of diminishing returns". the mutated virus cells are unable to reproduce properly, and each successive generation increases the abnormality making further generations even less viable. Eventually those mutated virii die off and, without producing viable offspring, eventually (I'm not a scientist so I can't tell you at what rate) this mutated virus is effectively gone.

of course, all the HIV that didn't mutate is still swirling around. ::)

edited to add:
by the way, in over 20 yrs with AIDS, I had never heard about this kind of HIV mutation degradation either. Until I moved from OH to SC and switched docs. This doc wanted to trade out the videx ec with truvada to reduce the pill load and allow one dosing time a day, instead of taking pills morning and night. When I freaked out about moving to a med that a mutation made uneffective, he gave me some links and explained this mutation was one that actually caused the HIV to die off without reproducing well. Needless to say I'm happy to see some of my mutant virus gone  ;D too bad those other mutations were more viable.  ::)
« Last Edit: May 25, 2010, 07:40:48 AM by leatherman »
leatherman (aka mIkIE)


chart from 1992-2013; updated 2/09/13  Reyataz/Norvir/Truvada

 


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