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Author Topic: GALT 25 years on?  (Read 27576 times)

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Offline alisenjafi

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GALT 25 years on?
« on: August 06, 2006, 12:35:29 pm »
In the interest of not further hijacking the tread   HIV Hides In gut to escape treatment 
http://forums.poz.com/index.php?topic=2332.0

The gist of the  post above has turned  from a question on why it took 25 years to equate the gut with the immune system and the technology that HIV Worker says just came about to look into GALT:

and you are saying they didn't look because either the scientists were too stupid or that the political climate that existed and still exists excludes adequate funding for HIV - so people can't afford to ask these questions?

R
Gee  can you point out anywhere that anyone BUT you brought up stupid?


Quote
that the political climate that existed and still exists excludes adequate funding for HIV -

Not only is funding being slashed but the money that are left are going into policies such as buying abstinence rings for kids. Do you feel this is money well spent?
Here are some views of this administrations contridictions on it's AIDS policy



http://www.thenation.com/doc/20041220/kaplan

http://www.thenation.com/doc/20040712/ireland

http://www.theage.com.au/articles/2003/02/09/1044725671018.html

http://www.washingtonpost.com/wp-dyn/content/article/2006/04/04/AR2006040401628.html

http://www.laweekly.com/news/news/taking-the-hypocrites-oath/2581/

http://www.thebody.com/atn/402/bush_aids.html

http://www.wsws.org/articles/2003/oct2003/aids-o09.shtml

http://query.nytimes.com/gst/fullpage.html?sec=health&res=9C05E1DD123EF930A35751C0A9679C8B63

Cheers
Johnny
« Last Edit: August 06, 2006, 04:14:12 pm by alisenjafi »
"You shut your mouth
how can you say
I go about things the wrong way
I am human and I need to be loved
just like everybody else does"
The Smiths

Offline HIVworker

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Re: HIV Worker; Bush on AIDS
« Reply #1 on: August 06, 2006, 01:00:42 pm »
Well, here is what I meant by stupid...

On the topic of finding out HIV replicates in the gut...J220 said...

It took scientists 25 years to discover this....

When asked what it meant he said...

Quote
Regardless, it's a fact. And the statement can be read in a variety of ways, for example, it can be meant as a comment on how insidious the virus is, while it can also be meant in the content that yes, researchers have been incompetently behind the curve for all these years. It's all in the eye of the beholder. But for the record, I did mean it in the latter sense.

If that doesn't indicate stupid, I don't know what does. Stupid means incompetently behind the curve. So that takes care of that.

DO NOT ask me to defend the current government funding of HIV nor the Bush administrations policy on HIV spending.

I guess it boils down to who you consider as 'them'. If them is the politicians that try and inject their political spin on HIV issues, then that is not what I am arguing. If you want to consider 'them' to = government spending then you can argue on your own. Government policy has never come into my work nor has it stopped me from getting government grants until the recent NIH spending cuts that hit every aspect of scientific research from physics to biology.

The reason it has taken 25 years to get to conclusion that the gut (lungs and brain) are important for HIV is due to the sensitivity of assays designed to look for replicating virus. It wasn't until 1996 that we had a decent viral load test, let alone to find a single cell with replicating virus in a body of others. My comment was in reply to J220's one about scientific incompetence and I am not going to be drawn on the rest of these issues as it was not the direction of either J220 or my posts. So take your own agenda elsewhere and take my name off this post.

R
« Last Edit: August 06, 2006, 01:02:26 pm by HIVworker »
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline aztecan

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Re: HIV Worker; Bush on AIDS
« Reply #2 on: August 06, 2006, 01:23:53 pm »
Well, to add my particular spin on things:

The fact it took 25 years to uncover this information is not surprising. Until a decade or so ago, gluten intolerance was virtually unknown. But today, it is now believed a fair percentage of people suffer from this condition.

Researchers have worked for years isolating, studying and finding many of the quirks of HIV. This doesn't imply stupidity. Just as not uncovering the differences between HIV in the blood and HIV in the brain was not stupidity. This is a learning process that will continue.

I think the salient point of this thread is the cuts in funding for research and the redirecting of moneys to other, futile, feel-good programs that makes Middle America comfortable.

ASOs and other organizations are increasingly having to prove their expenditures are valid - even though in some cases the degree of proof required approaches ludicrousy - or face funding cuts.

This all comes at a time when "abstinence only" programs and "faith based" organizations are raking in the dough for the previously described abstinence rings and other "just say no" ideas that are not only useless, but forego essential education regarding HIV prevention.

In solidarity,

Mark

(Edited because I should know better than to write in the heat of the moment.)
« Last Edit: August 06, 2006, 03:25:37 pm by aztecan »
"May your life preach more loudly than your lips."
~ William Ellery Channing (Unitarian Minister)

Offline HIVworker

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Re: HIV Worker; Bush on AIDS
« Reply #3 on: August 06, 2006, 01:34:32 pm »
Before this goes too far...

I totally agree with everything that has been said about funding. More is needed, not less.

But this discussion I was having in the other thread was not to do with Bush and telling people not to have sex. It was to do with the suggestion that it took 25 years of HIV research to find out the gut was important. I know many researchers who have held NIH grants that have been working on this very problem and it took the advent of some nifty tools to unlock this secret. It's not a black and white problem and not one that you can blame the government for. It's a tricky thing to find a few cells in several trillion that harbor active replication and the fact it took so long wasn't due to the incompetence of scientific researchers. THAT was the only thing I was taking issue with.

I am not stopping you going down the government bashing path or complaining about lack of funds, but PLEASE, PLEASE don't associate my name with someone who is agreeing with anything that is said in those links. Don't take my words out of context and suggest I somehow agree with everything that has gone on for 25 years - of Regan only saying once that HIV was a problem etc. My discussion had NOTHING to do with that.

I was saying that the men and women who do the work - and have been doing so since the start of this disease - are not incompetent or behind any curves. Our lives are made difficult by the funding problems - that I will agree. But I was trying to answer J220s comments that I stuck up in this quote. The notion that researchers are behind the curve in HIV. I don't believe it is so, so I was arguing that point.

So please take my name off this thread as it is a misrepresentation of what I was saying.

R
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline aztecan

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Re: HIV Worker; Bush on AIDS
« Reply #4 on: August 06, 2006, 02:01:06 pm »
R,
Sorry if my post sounds like government bashing. It was, to be sure. But, in the initial post of this thread, several links are provided and describe the dichotomy between Bush-speak and Bush reality.

I already know of your dedication to research in this field. I also do not in any way intend my post as a denigration of the efforts of researchers.

On the contrary, as I pointed out, HIV research is a progression. I could not expect all of the answers and fully expect more information to come to light as time passes.

But I take, for a variety of reasons, a very street-level view of HIV/AIDS. While research is important, crucial in fact, its clinical nature often makes it difficult to easily equate new discoveries to the life-and-death issues facing those living with HIV.

In other words, knowing that HIV hides in the gut is interesting, but more research is needed to find out the implications of this knowledge.

The final paragraph of the post opened the door for my comments.

Quote
Not only is funding being slashed but the money that are left are going into policies such as buying abstinence rings for kids. Do you feel this is money well spent?

Speaking solely for myself, the answer is no!

HUGS,

Mark
« Last Edit: August 06, 2006, 03:22:44 pm by aztecan »
"May your life preach more loudly than your lips."
~ William Ellery Channing (Unitarian Minister)

Offline alisenjafi

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Re: HIV Worker; Bush on AIDS
« Reply #5 on: August 06, 2006, 02:19:31 pm »
Again R I brought up how  HIV history has more to do with politics and phony morality than true science.
While you take incompetence to be synonymous with stupid, it doesn't though interesting enough bush does!
Those links were put there to back my position. More funding is needed but not to promote agendas. There are scientist who deny evolution- what does that tell you?

Quote from: HIVworker on Today at 09:39:42 AM
and you are saying they didn't look because either the scientists were too stupid or that the political climate that existed and still exists excludes adequate funding for HIV - so people can't afford to ask these questions?
The first part isn't even relevant to my post and to the second part, what good is giving millions of dollars , if the people getting it don't even acknowledge evolution. It isn't just the money but how it is spent.
Cheers
Johnny
"You shut your mouth
how can you say
I go about things the wrong way
I am human and I need to be loved
just like everybody else does"
The Smiths

Offline Joe K

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Re: HIV Worker; Bush on AIDS
« Reply #6 on: August 06, 2006, 02:32:32 pm »
Blanket statements regarding anything do more damage than any dialogue regarding an issue.  For J220, or anyone to even think. let alone post, that all the scientists working on HIV have been behind any learning curve, just makes them part of the problem.  I have been poz for a very long time and I have worked with hundreds of doctors, scientists, clinicians, etc., and I defy anyone to find more than a handful of those hundreds who may have been incompetent.

Instead, what I have witnessed are the breakdowns of many people treating and researching HIV, because as we discover more, we sadly realize how insidious HIV can be and how limiting our own science can be in combating it.  If you have some backup data, or could point to case studies or ANYTHING other than his own speculation on the competency of scientists, his comments could be evaluated.

As it is, his comments are just mean spirited, inflammatory and do nothing to further a dialogue on this issue.  What I find most offensive however, is that someone with HIV could truly believe such drivel and he should be ashamed of himself in besmirching the reputations of the thousands of scientists who have given all of what we have today.

If you want to discuss an issue, then either include all the variables (including funding) or keep your discussion focused.  Stereotypes are just plan foolish.

(Edited to remove mean and stupid statements.)
« Last Edit: August 07, 2006, 05:04:53 pm by killfoile »

Offline HIVworker

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Re: HIV Worker; Bush on AIDS
« Reply #7 on: August 06, 2006, 03:11:33 pm »
I don't know what your agenda is alisenjafi, but it has little to do with anything I have said. I was trying to get to the bottom of what J220 was saying, not you. You have your own political agenda and you should explore that in this thread. Just take my name off it as it has little to do with anything I have discussed.

I urge you to look at Joe's comments as he seemed to grasp it very well (as usual). You again try and steer it towards Bush and we weren't discussing that - you were. I was asking, in that quote you put of mine, if this is what J220 was saying - because if it was my next comment was that while I may or may not agree with that standpoint, it had little to do with scientists being on or near the 'curve'. Don't use my comments to bolster some link to the government. I submit that you didn't grasp the gist of the comment and are merely trying to put your own spin on it.


R
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline alisenjafi

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GALT 25 years on?
« Reply #8 on: August 06, 2006, 04:03:10 pm »
R
First off my confusion comes from the fact that your response came after my post. It might have been more clear if you addressed your post to him. I could only read that it was directed also at me since I was the one bringing up politics into the thread.

Secondly when asked simply why it took so long, you went on about something else. Why not either give an explanation or start a new thread on how some people  feel about researchers and scientist.
« Last Edit: August 08, 2006, 08:21:31 pm by alisenjafi »
"You shut your mouth
how can you say
I go about things the wrong way
I am human and I need to be loved
just like everybody else does"
The Smiths

Offline HIVworker

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Re: GALT 25 years on?
« Reply #9 on: August 06, 2006, 04:29:50 pm »
My apologies for the confusion. Thats the problem with internet forums.

I've promised to do all of that in the original post after clearing up the discussion with J220. As it is a review, it will take me a few days. However, look for it in that post.

R
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline lydgate

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Re: GALT 25 years on?
« Reply #10 on: August 06, 2006, 06:46:27 pm »
Seconding Joe. For the reasons he's given and another.

This seems to be another instance where the kneejerk cynicism (and yes, I understand why there is cynicism in the first place) of some people in the HIV community is a general disservice. The argument used inevitably derives from some position of Ideological Overdetermination; and this is ultimately traceable to some theory of base and superstructure. (The famous dictum: "It is not the consciousness of men that determines their being, but, on the contrary, their social being that determines consciousness.") The progress of science must be determined by the dominant ideology; this is the given, the axiomatic premiss. With that in hand, any putative failure of science can quite logically be ascribed to the awfulness of the current base-ideology.

This isn't valuable history of science: it's a venting of understandable bitterness, and it's scapegoating.

Don't think for a minute that I dismiss all Left-inclined interpretations of the history of science. Or, for that matter, of the history of HIV. But I find the dogmatic and crude sloganeering that sometimes passes for Leftist history of science to be tiresome at best, offensively distortional at worst.

Jay



« Last Edit: August 06, 2006, 06:51:09 pm by lydgate »
Her finely-touched spirit had still its fine issues, though they were not widely visible. Her full nature, like that river of which Cyrus broke the strength, spent itself in channels which had no great name on the earth. But the effect of her being on those around her was incalculably diffusive: for the growing good of the world is partly dependent on unhistoric acts; and that things are not so ill with you and me as they might have been, is half owing to the number who lived faithfully a hidden life, and rest in unvisited tombs.

George Eliot, Middlemarch, final paragraph

Offline J220

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Re: HIV Worker; Bush on AIDS
« Reply #11 on: August 07, 2006, 03:07:02 am »
Fair enough, Joe (and thanks for modifying the post).

Now, my question is (politically-incorrect, admitedly blanket statement aside) specifically about the GALT discovery. Does anyone know, if in fact GATL accounts for 70% of the immune system, why was this never looked at before? It just seems odd. Perhaps it is in fact a function of new testing capabilities, as HIVworker has implied but not yet proven. If that is that case, then I stand corrected. But from what I have read on the article nowhere does it say that they were able to detect the gut-resevoir thanks to new or special assays. All it says is that they took GALT samples, and measured for T-cells levels. Does anyone know if this discovery was the result of new technology, or simply that someone finally had the thought to look there? Thanks, J.

[Edited for 100% of content]
« Last Edit: August 07, 2006, 06:18:25 pm by J220 »
"Hope is my philosophy
Just needs days in which to be
Love of Life means hope for me
Born on a New Day" - John David

Offline lydgate

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Re: GALT 25 years on?
« Reply #12 on: August 07, 2006, 04:02:39 am »
Just to clarify: J220, when I said I seconded Joe I didn't mean to imply that you were flaming (in the relevant sense  ;) ). On the contrary, I've always respected your civility and humor on these boards. I'm relatively new to the world of online forums, and I've been surprised how often disagreement turns into rancor and debate degenerates into invective.

Jay
Her finely-touched spirit had still its fine issues, though they were not widely visible. Her full nature, like that river of which Cyrus broke the strength, spent itself in channels which had no great name on the earth. But the effect of her being on those around her was incalculably diffusive: for the growing good of the world is partly dependent on unhistoric acts; and that things are not so ill with you and me as they might have been, is half owing to the number who lived faithfully a hidden life, and rest in unvisited tombs.

George Eliot, Middlemarch, final paragraph

Offline ndrew

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  • ....-.-.-.-.-.....
Re: GALT 25 years on?
« Reply #13 on: August 07, 2006, 06:04:05 am »
Researchers are no more infallible than anyone else.  They are just as prone to incompetence, careerism, profiteering, greed, dishonesty and even stupidity.  I think researchers and the institutions that support them should be critiqued, as much as praised.  I think we should ask tough questions and proffer high expectations and express concern and dismay... AND CHALLENGED!

"The trouble with specialists is that they tend to think in grooves." -Elaine Morgan

"All increase in knowledge, every advance in science, represents a redrawing of the boundaries of the unknown." -Fred L. Polak, Dutch sociologist and politician
 
"If you go through life convinced that your way is always the best, all new ideas in the world will pass you by." -Akio Monta, co-founder of the Sony Corporation




Offline J220

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Re: GALT 25 years on?
« Reply #14 on: August 07, 2006, 02:25:39 pm »
Sorry for the confusion, Lydgate, I was directing the initial, now-edited post at Joe...we already addressed and resolved the issues I raised, I thank him for that, and you for your kind post. Cheers, J.


[Edited for 50% of content]
« Last Edit: August 07, 2006, 06:19:29 pm by J220 »
"Hope is my philosophy
Just needs days in which to be
Love of Life means hope for me
Born on a New Day" - John David

Offline Lis

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Re: GALT 25 years on?
« Reply #15 on: August 07, 2006, 11:55:07 pm »
i suspect that most of the attitudes exhibited here are the reason that scientists like R cant be left to find a solution... there is always a pissant that think he knows more!!!

ROCK ON HIV WORKER!!!!! THANK YOU FOR WHAT YOU DO!!!!!

lisbeth... the girl who should be dead by now..... but thanks to research.... I'm still here to be a bitch!!
poz 1986....

Offline alisenjafi

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Re: GALT 25 years on?
« Reply #16 on: August 08, 2006, 07:17:43 am »
LIS- please read the thread
http://forums.poz.com/index.php?topic=2332.0
Both J220 and I asked what we deemed 2 simple questions
1) Being an integral part of the immune system why did it take so long to focus on GALT?
  This might even be It was already focused on but the technology wasn't there - or some other reason.

2) If it is new technology what is that technology?

I even admitted to being an ignoramus on this subject and was hoping it would be explained so I can make better choices for my health-say besides just eating healthy which in itself is a blanket statement.

Just because one is happy in their  ignorance doesn't mean the rest of us have no right ask questions that might be  detrimental to our health or anyone should take it as an attack on their profession. 

This thread wasn't started to bash anyone  but defend my view ( and no one else ) on the history of HIV.  I would recommend people view the PBS shows on AIDS for a start. As well as read some of the links I provided.

Ndrew, now that we have christian lawyers, pharmacists , educators and politicians , my fear is it won't be long before America has christian scientists who since not believing in evolution will take us god knows where (pun intended)

Btw after getting my last labs results back my doc asked me to see an endocrinologist.  Because of my HDL coming in at 26 and triglycerides at 190.I knew this was going to be a waste of time.
Well first I wait an hour longer than my appointment when I meet the guy ( who was very nice). He was writing things down as we talked. I told him what I have been doing to my diet and what I eat.
He then shook my hand threw the paper in the garbage and said because I was so aware of my diet there was no reasons to reschedule any more consultations. WHAT A WASTE OF TIME.
Cheers
Johnny- knowledge is  empowerment
« Last Edit: August 08, 2006, 08:22:43 pm by alisenjafi »
"You shut your mouth
how can you say
I go about things the wrong way
I am human and I need to be loved
just like everybody else does"
The Smiths

Offline HIVworker

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Re: GALT 25 years on?
« Reply #17 on: August 08, 2006, 07:44:21 am »
When someone writes that HIV scientists are seriously behind the curve, that isn't a perceived feeling on my behalf - that's an actual feeling that someone expressed that I was responding to.

But seriously, will this historical review alter what medical choices you make?

On the topic of so called Christian scientists, it is true that there are people who push their own agenda. However, someone somewhere will come up with a cure. If big pharma companies and the government want to quash research by implementing a religious based agenda then I for one will move out the country to a place (like Europe) that doesn't force such issues. I've moved countries before for science and I wouldn't hesitate to do so again. A lot of other scientists feel the same.

If HIV science loses out to religious fundamentalism in America then ultimately it will be their loss. The cure will be found elsewhere and America and any other company that forces the status quo based on religious beliefs will lose all of their profits and that part of the company will fold. An ironic survival of the fittest..

R
NB. Any advice about HIV is given in addition to your own medical advice and not intended to replace it. You should never make clinical decisions based on what anyone says on the internet but rather check with your ID doctor first. Discussions from the internet are just that - Discussions. They may give you food for thought, but they should not direct you to do anything but fuel discussion.

Offline J220

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Re: GALT 25 years on?
« Reply #18 on: August 08, 2006, 02:25:20 pm »
All the politics aside, HIV worker, did you find the answer about the technology behind the GALT discovery? Was is due to new technology or not?? Also, what existing medication, if any, could be used to address viral loads in GALT? (if you know, of course). The article mentioned anti-inflamatories....J.
« Last Edit: August 08, 2006, 02:50:44 pm by J220 »
"Hope is my philosophy
Just needs days in which to be
Love of Life means hope for me
Born on a New Day" - John David

Offline alisenjafi

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  • They say HIV comes from monkeys!
Re: GALT 25 years on?
« Reply #19 on: August 08, 2006, 08:37:30 pm »
R - I stand corrected than and deleted the comments on "the perceived feeling"

As for making decisions. while there is no scientific evidence about corn syrup and now reading some "scientist" say there is no harm, I go out of my way to find food without the sugar crack. Yes I read both sides of the argument but long ago concluded ( remembering how goldfish blew up on corn) that this stuff is just plain no good.
Instead of taking a multi synthetic vitamin I chose bee pollon and propolis which  give me a hell lot more energy, make me feel better and got rid of that cloudyness that Sustiva gives one. Which btw my first doc said would go away, and in the end I got used to it but it was always there. A multi vitamin never did that.
So if it comes out that by using a colon cleaner, fasting  or whatever the end result of GALT studies brings , I can figure if it is worth it.
Johnny
"You shut your mouth
how can you say
I go about things the wrong way
I am human and I need to be loved
just like everybody else does"
The Smiths

Offline Tim Horn

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Re: GALT 25 years on?
« Reply #20 on: August 10, 2006, 06:51:41 am »
I really need to chime in here.

What's really bothering me here is the assertion that the discovery of HIV replication in GALT -- and the limited effect of antiretroviral therapy on HIV replication in GALT -- took 25 years to discover. 

I've seen this referenced in a few lay/mainstream articles... and that fact is, it's a totally BUNK statement. In fact, a number of mainstream media accounts of this research have a lot to be desired. 

Dating back to 1988, researchers documented that CD4+ cells in the gut are highly susceptible to HIV infection and, given the sheer number of receptors on their cells, likely play a role in an inflammatory response to HIV infection:

  • Zeitz M, Greene WC, Peffer NJ, et al. Lymphocytes isolated from the intestinal lamina propria of normal nonhuman primates have increased expression of genes associated with T-cell activation. Gastroenterology 94(3):647-55, 1988.

In 1993, Donald Kotler -- a very well-respected researcher who has done a lot of work in HIV-related gastroenterology -- showed that HIV infection can lead to inflammation of immune system tissues in the gut, which may lead to problems like diarrhea and poor absorption:

  • Kotler D, Reka S, Clayton F. Intestinal mucosal inflammation associated with human immunodeficiency virus infection. Diges Dis Sci 38(6):1119-27, 1993.

Then we learned how incredibly large and diverse the population of immune system cells is in the gut:

  • Zeitz M, Ullrich R, Schneider T, et al. Cell differentiation and proliferation in the gastrointestinal tract with respect to the local immune system. Ann NY Acad Sci 733:75-86, 1994.

In 1998, data were reported indicating that GALT -- in laboratory rodents -- truly is a major reservoir of SIV (simian immunodeficiency virus) infection:

  • Veazey R, DeMaria M, Chalifoux L, et al. Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science 280:427-31, 1998.

In 1999, we received confirmatory news that HIV replication is very much detectable in the GALT of humans:

  • Poles M, Elliott J, Brown S, et al. HIV-1 is detectable in mucosal biopsies in patients with undetectable plasma viral loads [Abstract 160]. 6th Conference on Retroviruses and Opportunistic Infections, Chicago, 1999.

And over the past seven years, there have been several papers -- many of which were produced by researchers associated with the University of California system (including some of the researchers associated with this study in question) -- illlustrating HIV's activity in GALT and confirming that GALT truly is a unique sanctuary of HIV replication.

The newest research simply builds upon what we've KNOWN for close to 20 years!  This was the first study to prospectively follow study volunteers over time.  In other words, it looked at GALT samples collected before treatment was started and three years later, after being on treatment for awhile.  And from this research, we learned that treatment has a limited effect on HIV replication in the gut. 

There's no denying the significance of this research, as it illustrates that antiretroviral treatment -- as we currently know it -- isn't all that it's cracked up to be in terms of halting HIV replication in GALT. 

While its not entirely clear what these findings mean for HIV-positive people, the researchers hint at the possible need for early HIV treatment, intestinal biopsies, and the use of anti-inflammatory medications to effectively manage HIV infection in the gut.  However, IMHO, there is a lot more to learn about HIV replication in GALT before treatment guidelines are revised or intestinal biopsies are recommended to people living with HIV and their healthcare providers. Is HIV replication in the gut, while someone is on HIV treatment, a cause of drug resistance? Would improved HIV treatment activity in the gut really provide the immune system with greater protection against AIDS-related opportunistic infections? Which HIV medications are most effective against HIV in GALT? Will early treatment, the use of anti-inflammatories, and intestinal biopsies actually help HIV-positive people live longer, healthier lives?

These are just some of the questions that need to be addressed in clinical trials before these suggestions are put into practice.  And what's really important here is that this research -- along with all the other GALT-related research completed over the past two decades -- will hopefully pave the way for additional studies to answer these questions. 

Tim Horn
« Last Edit: August 10, 2006, 08:01:06 am by Tim Horn »

Offline newt

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Re: GALT 25 years on?
« Reply #21 on: August 10, 2006, 07:00:04 am »
Indeed, & here here!

Prof. Brian Gazzard, Consultant Physician and Research Director at the St. Stephen’s Clinic, London, was originally a gastro-enterologist, which is how he got into HIV medicine, seeing too many young people with weird and unusual stomach complaints...
"The object is to be a well patient, not a good patient"

Offline alisenjafi

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Re: GALT 25 years on?
« Reply #22 on: August 10, 2006, 07:09:52 am »
Quote
The newest research simply builds upon what we've KNOWN for close to 20 years!
Thanks Tim all I was looking for was background into the GALT studies. Part of my ignorance comes from the fact when I see the doctor ( all 5 minutes) or go for blood test, while I am being tested on my reaction to my meds to my body , very little was explained to me on the this area.
Cheers
Johnny
« Last Edit: August 10, 2006, 07:14:07 am by alisenjafi »
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Offline Tim Horn

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Re: GALT 25 years on?
« Reply #23 on: August 10, 2006, 08:57:34 am »
Johnny --

Doctors' time contstraints notwithstanding, a primary issue why most docs don't discuss GALT (or why the may look at you funny if you bring up the subject) is because it's really not known what they're supposed to do about it.  In fact, I would argue that most docs -- notably those who aren't involved in research or keep up with all the nitty-gritty data emerging from laboratories (and there's a lot of this) -- are even aware of the nuances associated with HIV in GALT. 

Like I said above, we really don't know what the clinical significance of this GALT research is.  If we are to go changing the diagnostic and treatment paradigms currently in place, we really need to see concrete data illustrating -- in black and white -- why GALT must be taken into consideration by docs.  Right now, all we really have is a lot of basic science work... research suggesting that GALT is a force to be reckoned with in the grand scheme of things.  But we need a lot more clinical research to prove this -- research confirming that early treatment helps protect GALT; research looking into which antiretrovirals are better at penetrating GALT than others; research showing that starting treatment early, or using GALT-penetrating antiretrovirals, makes a REAL DIFFERENCE in HIV-positive lives, such as delayed treatment resistance, a better chance of keeping viral load undetectable, greater increases in CD4+ cells, fewer HIV-related complications (including diarrhea and other diseases that can affect the gut), and longer survival. 

Without knowing any of this, having everyone scramble to talk with their doctors, demand GALT biopsies, start early treatment, or get themselves onto GALT-penetrating therapy (again, we don't even know what this would constitute, really), is nonsensical. 

Even though GALT-related research has been going on for approximately 20 years, I honestly believe the research is still in its infancy.  Now comes the really challenging, Eureka-making stuff -- doing the research to determine what this stuff really means for HIV-positive people... and the docs who care for them.

Cheers,

Tim Horn   
« Last Edit: August 10, 2006, 09:17:53 am by Tim Horn »

Offline gerry

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Re: GALT 25 years on?
« Reply #24 on: August 10, 2006, 09:46:37 am »
Thanks, Tim, for that informative summary.

There is a good brief review of this topic in the May 2006 Hopkins HIV Report.  Hope the editors don't mind the copy and paste job.



HIV-1 Infection of CD4+ T Cells in the Gut

By Megan Wind-Rotolo Ph.D. and
Joel N. Blankson M.D., Ph.D.

Clinicians and researchers have used peripheral blood as a convenient way of obtaining information on CD4 cell counts and the extent of viral replication in HIV-infected individuals. However, it should be noted that only 2% of the total body store of lymphocytes circulate in the peripheral blood; the other 98% reside in lymphatic tissue scattered throughout the body. Gut-associated lymphatic tissue (GALT) represents the single largest pool of lymphocytes, and as such, it is not surprising that it is a major target for HIV infection. In the past few years several major observations have been made regarding GALT. First, there is a massive depletion of GALT CD4 cells during primary infection. These cells are affected to a much higher degree than CD4 cells in the peripheral blood [Veazey R, et al. Science 1998; 280:427-431, Brenchley JM, et al. J Exp Med 2004;200:749-759]. Furthermore, there is little or no reconstitution of these cells after the initiation of HAART in chronically infected patients [Guadalupe M, et al. J Virol 2003;77:11708, Mehandru S, et al. J Exp Med 2004;200:761-770]. Finally, HIV-1 DNA and RNA can be detected in rectal biopsies from patients on HAART with undetectable plasma viral loads, suggesting that GALT CD4 cells can serve as a reservoir for HIV infection [Anton PA, et al. AIDS 2003;17:53-63]. At this year’s CROI there were numerous oral presentations regarding this interesting topic.

Brenchley and colleagues determined the frequency of HIV-infected CD4 cells in the gut of HIV-infected patients who had been on HAART for up to 3 years [Abstract 38]. They found that on average the frequency of infection of GALT CD4 cells was 10 times higher than that of CD4 cells from blood. Memory CD4 cells from the gut were also shown to be capable of producing virus, and while there was no direct evidence of active replication, it was concluded that gut depletion is likely caused by ongoing infection of local CD4 cells. In addition, few HIV-specific CD8 cells were found in the gut compared to the blood, indicating that the proposed ongoing viral replication in GALT is associated with a lack of local HIV-specific immunity.

Baker and colleagues also measured the frequency of CD4 cells in GALT and showed that the percentage of CD4 cells in this region is 50% lower in HIV-infected patients compared to non-infected controls [Abstract 41]. Interestingly, while there was a significant increase in peripheral CD4 cell counts after 6 months of HAART, there was no increase in the percentage of GALT CD4 cells. This is more evidence that CD4 cell depletion in the gut may not be reversible in chronically infected patients. The effect of depletion of gut CD4 cells is unknown, but there was an incidental finding of intestinal polyps in 6/31 relatively young HIVinfected patients, including 1 precancerous lesion and 1 case of cancer.

HIV-infected patients who started HAART within 3 weeks of infection were shown to be able to repopulate memory CD4 cells in the gut [Dandekar, et al. Abstract 39]. The initiation of HAART was also associated with a lower frequency of infection of GALT CD4 cells. The expression of genes in the gut of patients who started HAART early was compared with that of patients who started HAART at later time points. Those who were started HAART early showed lower expression of inflammation and cellular activation genes and increased expression of mucosal repair and regeneration genes. These results led to the conclusion that the disruption of the gut microenvironment causes the depletion of CD4 cells.

Having shown a high frequency of infection of GALT CD4 cells, Douek and colleagues looked at other mucosal sites as well [Abstract 166]. Massive depletion of CD4 cells in the lung has previously been described in pathogenic SIV infection of Rhesus macaques [Picker LJ, et al. J Ex Med 2004:200:1299-1314.) The investigators have begun to study the effect of HIV on CD4 cells of the lung by analyzing cells from brocheoalveolar lavage of HIV-uninfected and HIV-infected patients. Preliminary data indicate that the pattern seen at this site differs markedly from that observed in the GALT. There is no depletion of CD4 cells associated with HIV infection; instead, an increase in the number of both CD4 and CD8 cells is seen. In contrast to the high frequency of infected cells in the GALT, the frequency of infection of lung CD4 cells is relatively low (comparable to the frequency of infection of peripheral blood CD4 cells). In addition, HIV-specific CD8 and CD4 cell responses are preserved at this site, and it was proposed that this local immunity may explain the low cellular viral loads and the preservation of normal CD4 cell counts.

What are the clinical consequences of CD4 cell infection in GALT? While it appears that the poor reconstitution of CD4 cells at this site is not associated with major GI symptoms in most patients on HAART, the relatively high frequency of pathology seen by Baker and colleagues is concerning [Abstract 41]. Confirmatory studies in larger cohorts of patients are needed. If reconstitution of GALT CD4 cells is important, then the work of Dandekar and colleagues [Abstract 39] would suggest that there is a major advantage to early treatment with HAART. The GI tract appears to be the major target in primary infection; therefore, it follows that preventative vaccines will need to induce strong mucosal immunity in order to be effective. The high frequency of infected cells in the GALT has been interpreted by some investigators to be evidence of ongoing replication in patients on HAART. If this is correct, it could potentially explain treatment failure in some patients. This issue clearly needs to be definitively addressed, and tissue drug levels at this site should be measured. Finally, investigators working on eradication of HIV infection have based their models on the rate of decay of latently infected cells in the peripheral blood. Nothing is known about the half-life of infected cells in GALT. As these cells and infected cells from other anatomical reservoirs are studied, major revisions in these models will likely be needed.


Offline lydgate

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Re: GALT 25 years on?
« Reply #25 on: August 10, 2006, 06:38:55 pm »
Thanks Tim and gerry... like Matt and R, you guys really are an asset to these boards...  ;D
Her finely-touched spirit had still its fine issues, though they were not widely visible. Her full nature, like that river of which Cyrus broke the strength, spent itself in channels which had no great name on the earth. But the effect of her being on those around her was incalculably diffusive: for the growing good of the world is partly dependent on unhistoric acts; and that things are not so ill with you and me as they might have been, is half owing to the number who lived faithfully a hidden life, and rest in unvisited tombs.

George Eliot, Middlemarch, final paragraph

 


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