New AIDS drugs used in search of a cure

[mark86]

Just found this, quite interesting. What do people think ?

http://www.bloomberg.com/apps/news?pid=20601087&sid=a.0x1mlV37Qw&refer=home


Mark86

[Central79]

It will be interesting to see if this works - it's cool that they're starting to think they have drugs powerful enough to have a shot at this. After the initial disappointment of HAART not being able to totally eradicate viral reservoirs and deal with the latency issue and the pessimism following that I think this is a very positive step forward in trying to work out a regime that might allow a subset of HIV+ people to be cured. And then the rest of us...

Here are some more links:

http://www.aidsmap.com/en/news/0B610895-B3A6-4512-839B-BAC8151D4EBE.asp

http://poz.com/articles/1_11882.shtml

There's obviously a lot of scepticism in medical circles, which I think is right - we don't want a repeat of "CURE!" being splashed all across the Lancet like for valproic acid. But it's cool that they're having a go, trying to work out the mechanisms of latency and the decay of the curve and trying. I like that.

M.

[hahaha]

There's obviously a lot of scepticism in medical circles, which I think is right - we don't want a repeat of "CURE!" being splashed all across the Lancet like for valproic acid. But it's cool that they're having a go, trying to work out the mechanisms of latency and the decay of the curve and trying. I like that.
M.

I do think that it is possible.  My reasoning is as follows:

If you look at the experiment of Valproic + Fuezon which reduce about 85% of the HIV DNA attachment. It will be either Valproic or Fuezon that makes it happen. 

If Valproic is not the one that reduce the DNA attachment, then it shall be Fuezon (CCR5 blocker) that does it.
Do remember that CD4 have a half life of 3-4 months, and do remember that active CD4 carry more HIV DNA then the resting one.  (These are all found by bio-scientist). 

Now by adding CCR5 blocker, it is possible that the new grown CD4  will be better protected. (without HIV attached to DNA)

Once new grown CD4 is being protected, we just let old CD4 die out gradually. 

Now, the only matter we need to concern, is those HIV hide in macrophage and nerve system, and brain and bone. 
There are medicine that is developing (from Biotron in Oz I think), that can stop macrophage produce HIV. 
We also need them to wait until HIV RNA in macrophage die out completely.  which takes in average about a year. 

So, Haarts + CCR5 blocker + macrophage inhibitors + time (die out of old CD4 and macrophage), may highly reduce the HIV incorporate in infected CD4). 

If the number is down to a very low amount.  Our body will then come up for some fighting mechanism, that kill the very very small amount.  (or maybe anti-PD-1 or NK will kick-in?)  Maybe with the help of vaccine, it can be completely purge off.

[ronaldinho]

I thought that eradicating HIV with antiretroviral was impossible, even theoretically speaking. Anyway, there has been a significant number of people who had mantained undetectable VLs for a long time and then tried STI (structured treatment interruption), so if HAART had any chance of eradicating HIV, i guess that by now we would have seen at least a few cases of HIV eradication among these people trying STI??

[thunter34]

So what's the story on the "for those who start treatment early" part?  I had millions of the little bastards in me and an official AIDS diagnosis from the get-go...so not an early starter.  Yet I am undetectable now and have been for awhile.  Is this saying that my case is a mathematical possibility or not? 

[Jake72]

What exactly does "early" mean?  Before seroconversion?  before AIDS?  Also, very early on, during acute infection, doesn't the viral load climb really high before coming back down?  So most people, even those treated "early," have had high viral loads at some point, even if they're not chronically high, right?

Also, people progress at different rates.  Someone could experience as much disease progression in six months as another person could experience in five years.

It's an interesting idea, and it'd be wonderful if it could somehow work out.  And Ronaldinho, you're right, STIs have shown that the infection usually bounces back eventually after treatment is discontinued.   Isn't the theory behind this new approach that conventional HAART would bring down the VL for years, then other, stronger meds would be added before the final treatment interruption?  Kind of a one-two punch as opposed to the "one punch" in standard STIs. 

[appleboy]

This is getting exciting!  There are so many new ideas and studies that are really pointing towards a cure.  So hopefully in most of our lifetimes we might see the cure or at least long term non medication treatment options.
AppleBoy

[Central79]

OK - first up we are talking about a small study, recently published that involved seven patients. The patients started HAART early - the average being 7 months after seroconversion. The HAART consisted of at least 1 PI + 2 NNRTIs and they were followed up and the decay curve of the viral reservoir measured over an average of 40 months follow-up.

The researchers found that the time taken for the viral reservoir to halve in size was 5 months. They worked out from this a theoretical point where there would be no viral reservoir left at about 7.7 years.

So HAART came out in 1996, and a cohort of people who have maintained viral suppression for about this time are going to be further studied, and maybe come off therapy to see what happens.

In addition, the NIH team under Dr Fauci are going to try the addition of new drugs, like integrase inhibitors and maybe T-20 to see if they can further close down on this time of 7.7 years, and maybe attempt a cure in a few years in people newly diagnosed.

There are a number of reasons to be sceptical:
1. In 4 out of the 7 patients there was a second phase of viral reservoir decline, which was much slower.
2. HIV may rarely persist in cells other than resting CD4 T-cells.
3. Circulating resting cells somewhat underrepresent infection in resting cells in the tissue.
4. Getting drugs into all body compartments is still an issue - brain, gut.
5. The presence of a very few cells remaining after therapy, would reignite infection.

For people with more established infection, their viral reservoirs are going to be bigger and more established, and present a more substantial problem.

I take hope from this study, because if you can cure a subset of patients, then the principle is sound. Then you can look at developing drugs that speed up the rate of viral reservoir depletion for people with longer HIV infection.

I'm not expecting a cure from this. It's a step towards curing newbies who get diagnosed early enough, but we will learn a lot about the viral latency and viral reservoir issues from it for the rest of us too.

M.

[bimazek]

this looks very exciting and encouraging, remember that the immune system is a Non linear system

(   http://en.wikipedia.org/wiki/Nonlinear  -- it is not just the sum of its parts, one example of which is a car engine, you can imagine that taking each part of the engine, as parts does not make the car go forward and it can break down and stop working when one or two or three of the parts are not working well, then the system, the engine shuts off and will not run, Crudely, a nonlinear system is one whose behavior is not simply the sum of its parts or their multiples.   ), meaning that

it may be possible to completely break down replicaiton reserveor without breaking down every part of the hiv habitate.

also when you add in vaccines -- and there are like 40 types being studied or more, and gene therapy another 40 types, and immune modulation antibodies etc, as well as Interluken or IG or something i met a guy at a poz social who flies back east for some interluken or immunoglobin or some new hiv therapy

when you add all these silver bullets i think there is hope for complete erradication...

but perhaps some of there new developments will give the human body the same ability of many animals now have to completely represses Retroviruses naturally with thier own immune system...

http://forums.poz.com/index.php?topic=7475.0

and when these new modifications -- called cd8 stimulators or CD8 re enegizers are developed, some are already approved by fda, then suppressing the virus with human bodies own immune system may be a posibility.

or even in combo with all the things mentioned above in the topic thread

remember only one in a million cd4 cells is even infected in first place
probably one in 700 trillion cd4 cells is even infected when viral load is undetectable

all cd4 cells infected when VL is at 50,000 only take up the head of a pin, very small "malignancy" the issue is it is distributed ... which we have been discusing

cd8 cells work great and repress virus great for 3 to 12 years and in some cases 20 years without meds why
because the cd8 cells do not get disfunctional, why do the cd8 cells get  disfunctional, seems to be a protein produced by hiv that tells the cd8 cell (via a receptor channel on surface) that the cd8 cell is not needed and should stop doing its job

also there is another chemical signal that tells the cd4 cells (non infected ones at that) to go back to lymph node and die off because the infection is taken care of

but that is how hiv is tricky, the infection is not taken care of, and the signal is a decoy or something

and the cd4 cells go to node and die off, and new fresh ones are produced and come into the body

this goes on for 5 to 12 years

finally the cd8 cells get overwhelmed by the signal to become disfunctional and

the cd4s are not produced fast enough

and so

i think all this together mean alot of hope

we just need to activate and get something done to get congress to put more money into research

[milker]

Thanks bimazek for your obvious effort to make a post with links and readable. I, and I'm sure others appreciate it.

Milker.