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Researchers shoot wing off HIV drug rationale


HIV hides in guts, immune to expensive ARVs

Years of hideous side effects for nothing?

“I thought you would be interested to read this article from The Times”, writes a thoughtful correspondent, MG, and indeed the latest effort by Sam Lister, the health correspondent of the Times of London, seems worth noting.

According to his story yesterday (Sat Jul 29) HIV hides itself in the intestines to beat drugs, ARVs (antiretrovirals) are now shown to have no effect on HIV in the guts, where the nightmare virus establishes itself securely to attack the 70% of the immune system located there.

The scientists found that the virus that causes Aids took hold in intestinal tissue of patients receiving antiretroviral therapy (ARV). There it continued to replicate and suppress the immune system even though blood samples showed that the drugs were working.

Professor Satya Dandekar, who led the study, said that, while ARV could be quite successful in reducing HIV’s presence in the blood, the virus still thrived. “The real battle between the virus and exposed individuals is happening in the gut immediately after viral infection,” she said. “We need to be focusing our efforts on improving treatment of gut mucosa, where massive destruction of immune cells is occurring.”

Professor Dandekar, head of the university’s department of medical microbiology and immunology, said that gut-associated lymphoid tissue accounted for 70 per cent of the body’s immune system, and that restoring its function was crucial to destroying the virus.

So why take ARVs at all, then, if HIV can and will easily hide out in the guts and do its dirty work on 70% of the body’s immune system cells there?

That’s too simple, according to the study authors at Davis, whose research is supported by the NIH. They do not come to this obvious conclusion. On the contrary, their prescription is to start treatment earlier.

Thomas Prindiville, the study’s co-author, said that starting treatment earlier significantly improved the chances of restoring immune function.

“If we are able to restore the gut’s immune response, the patient will be more likely to clear the virus,” Professor Prindiville said. “You can’t treat any infectious disease without the help of the immune system.”

How early is early? Judging from the monkey studies a year ago April that first suggested this line of thinking, because they found that simian immunodeficiency virus decimated immune cells in the guts of monkeys within days, early means patients should receive ARVs within a few days.

Those who keep up with the newsflow of this paradigm will recognize this as a contribution to the current campaign to expand testing to the entire population of the United States as soon as possible.

In fact, it takes us one step closer to justifying prophylactic medication for everyone “at risk” in the US. Except for one thing – the mysterious fact that this wholesale destruction within days of the 70% of our CD4 cells in our gut doesn’t seem to have any long term effect. Everything soon goes back to normal for as long as twenty or thirty years – however long the “latent” period is.

Granted that the report may be garbled but the item seems to show that there is no limit to how new findings can be twisted to serve the cause of what is no longer a scientifically based enterprise in any meaningful way.

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The Times July 29, 2006

HIV hides itself in the intestines to beat drugs

By Sam Lister, Health Correspondent

HIV can avoid the powerful drugs that sufferers take to destroy it by hiding in their guts, scientists have discovered.

The scientists found that the virus that causes Aids took hold in intestinal tissue of patients receiving antiretroviral therapy (ARV). There it continued to replicate and suppress the immune system even though blood samples showed that the drugs were working.

The scientists from California University said that results of their three-year study, published in the Journal of Virology, showed HIV treatments needed re-evaluation.

Professor Satya Dandekar, who led the study, said that, while ARV could be quite successful in reducing HIV’s presence in the blood, the virus still thrived. “The real battle between the virus and exposed individuals is happening in the gut immediately after viral infection,” she said. “We need to be focusing our efforts on improving treatment of gut mucosa, where massive destruction of immune cells is occurring.”

Professor Dandekar, head of the university’s department of medical microbiology and immunology, said that gut-associated lymphoid tissue accounted for 70 per cent of the body’s immune system, and that restoring its function was crucial to destroying the virus.

The study suggests that earlier ARV and the use of anti-inflammatory drugs could achieve this. It also urges gut biopsies on all patients receiving ARV as a way of monitoring their condition.

“We found a substantial delay in the time that it takes to restore the gut mucosal immune system in those with chronic infections,” Professor Dandekar said. “In these patients the gut acted as a viral reservoir that keeps us from ridding patients of the virus.”

Doctors have long relied on measuring HIV’s presence in the blood and T-cell counts. T-cells, also called T-helper cells, organise the immune system’s fight against viruses. However, their numbers are reduced when HIV enters the body, leaving carriers vulnerable to infection.

Earlier research by Professor Dandekar and her team supports the claim that patients with high numbers of T-cells in their gut tissue were likely to live longer.

Thomas Prindiville, the study’s co-author, said that starting treatment earlier significantly improved the chances of restoring immune function.

“If we are able to restore the gut’s immune response, the patient will be more likely to clear the virus,” Professor Prindiville said. “You can’t treat any infectious disease without the help of the immune system.”

The scientists followed ten patients receiving highly active antiretroviral therapy, known as HAART. Three of the patients were treated within six weeks of finding out they were HIV positive.

Here’s a more informed report from RxPG News:

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RxPG News

Jul 30th, 2006 – 02:34:25

HIV hides from drugs in gut, preventing immune recovery

Jul 30, 2006, 02:32, Reviewed by: Dr. Priya Saxena

“This is the first longitudinal study to show that, while current HIV therapy is quite successful in reducing viral loads and increasing T-cells in peripheral blood, it is not so effective in gut mucosa”

By University of California, Davis, UC Davis researchers have discovered that the human immunodeficiency virus, the virus that causes AIDS, is able to survive efforts to destroy it by hiding out in the mucosal tissues of the intestine. They also found that HIV continues to replicate in the gut mucosa, suppressing immune function in patients being treated with antiretroviral therapy–even when blood samples from the same individuals indicated the treatment was working.

“This is the first longitudinal study to show that, while current HIV therapy is quite successful in reducing viral loads and increasing T-cells in peripheral blood, it is not so effective in gut mucosa,” said Satya Dandekar, professor and chair of the Department of Medical Microbiology and Immunology at UC Davis Health System and senior author of the study.

“The real battle between the virus and exposed individuals is happening in the gut immediately after viral infection,” she said. “We need to be focusing our efforts on improving treatment of gut mucosa, where massive destruction of immune cells is occurring. Gut-associated lymphoid tissue accounts for 70 percent of the body’s immune system. Restoring its function is crucial to ridding the body of the virus.”

Results of the study suggest that patients being treated with antiretroviral therapy should be monitored using gut biopsies and that the gut’s immune function be restored through earlier antiretroviral treatment and the use of anti-inflammatory medications.

“We found a substantial delay in the time that it takes to restore the gut mucosal immune system in those with chronic infections,” Dandekar said. “In these patients the gut is acting as a viral reservoir that keeps us from ridding patients of the virus.”

Physicians treating HIV-infected patients have long relied on blood measurements of viral load and T-cell counts when choosing a course of treatment. Viral load is the number of viral particles in a milliliter sample of blood. T-cell counts reflect the number of CD4+ T-cells in the sample. These cells, also called T-helper cells, organize the immune system’s attack on disease-causing invaders. They are, however, the targets of the virus and their numbers decrease as the amount of HIV increases, leaving the body vulnerable to a variety of infections.

Last year, Dandekar’s team published a study of HIV-infected patients who, despite the lack of treatment, had survived over 10 years with healthy levels of T-cells and suppressed viral loads.

“We looked at their gut lymphoid tissue and did not see loss of T-cells there. This correlated with better clinical outcomes,” Dandekar explained.

Those results prompted Dandekar and her team to undertake the current study in which they set out to evaluate the effect of highly active antiretroviral therapy, known as HAART, on viral suppression and immune restoration in gut-associated lymphoid tissue. They followed 10 patients being treated with HAART, taking blood and gut samples before and after three years of treatment. Three of the patients were treated during four to six weeks of first being infected with the virus. The other participants were known to be HIV positive for more than one year.

Hoping to figure out why HAART does not work as well in the gut, Dandekar and her colleagues further examined the post-treatment of gut-associated lymphoid tissue samples. They found evidence of inflammation, which disrupts tissue function, promotes cell death and upsets the normal balance of gut flora. They also found that the activity of genes that control and promote mucosal repair and regeneration were suppressed, while the genes responsible for the inflammatory response were more active than in normal tissue.

Dandekar said these results suggest anti-inflammatory drugs may improve antiretroviral treatment outcomes. She also pointed out that genes involved with the repair and regeneration of gut-associated lymphoid tissue would make excellent drug targets.

Researchers then compared HAART outcomes in those who chose to be treated within the weeks of exposure to those with chronic infection. They discovered that newly infected patients had fewer signs of inflammation at the beginning of the study and experienced greater recovery of the gut mucosal immune system function by the end of it.

Dandekar and her colleagues are currently following additional patients being treated with HAART. Unpublished data on these patients supports the current findings, said Thomas Prindiville, a gastroenterology professor at UC Davis and a co-author of the study.

“What we continue to see is that restoration of immune function is more likely when treatment is started early,” said Prindiville. “Starting HAART before T-cell counts fall below 350 cells per cubic milliliter, would preserve immune function and hasten its full recovery.”

The team of physicians and researchers plan to keep testing ways of improving the efficacy of antiretroviral therapy in gut-associated lymphoid tissue. These include treating gut inflammation, starting treatment earlier and using gut biopsies to monitor treatment success.

“If we are able to restore the gut’s immune response, the patient will be more likely to clear the virus,” Prindiville said. “You can’t treat any infectious disease without the help of the immune system.”

– Results of the three-year study appear in the August issue of the Journal of Virology

jvi.asm.org

14 Responses to “Researchers shoot wing off HIV drug rationale”

  1. Dan Says:

    According to his story yesterday (Sat Jul 29) Professor Satya Dandekar, who led the study, said that, while ARV could be quite successful in reducing HIV’s presence in the blood, the virus still thrived. “The real battle between the virus and exposed individuals is happening in the gut immediately after viral infection” Wait up!The real battle?Red flag alert!Is professor Dandekar trying to tell us that after 22 years of HIV research, they’ve suddenly realized that the “real battle” is in the gut, immediately after infection?Also according to professor Dandekar…”gut-associated lymphoid tissue accounted for 70 per cent of the body’s immune system, and that restoring its function was crucial to destroying the virus”. Is this information about the immune system itself that is brand new? This sounds like an absolutely ground-breaking, revelatory new finding. After all these years, now they can really go after HIV. Wow, thank God they finally figured this out.Unfortunately, for those who’ve been following this hideous medical nightmare for years while only half-awake, they’ll see yet another carrot dangled in front of them, like hundreds of others that have been placed in front of them before. while ARV could be quite successful in reducing HIV’s presence in the blood, the virus still thrived This statement serves multiple purposes. First, you see ARV linked with the word successful . But… the virus still thrives (?). Give the public a momentary sense of hope, but keep the important paradigm-maintaining factors of medication (ARV) and an undefeatable virus in place. And in the vein of our Look Away Paradigm (thanks, Truthseeker), we need to turn our heads away from the illogic of calling something a success, when by their own admission it clearly isn’t.

  2. Truthseeker Says:

    Not sure why you are ignoring the apparent fact that she is telling the world that they have been wasting their time with ARVs for all these years, since the Virus has been attacking 70 per cent of the immune system freely all the time.

    Seems rather remarkable that we have a UC Davis Head of Department telling the world how the Virus has easily evaded medication all these years. If she is right then the Virus is apparently not doing much, so we may now pack up and go home and do something else with our lives, which is precisely what we have been saying all along.

    Long Live Satya!

    Love to see what Larry Altman is going to make of this.

  3. Dan Says:

    The words “real battle” gripped my attention.They’ve just admitted to 22 years of worthless research if they’ve failed to take into account where the real battle lies.Now, if they could just pull back a wee bit more…

  4. Martin Kessler Says:

    Could you direct me to the study that shows that HIV kills T-cells, CD4-cells, etc.? Inquiring minds want to know. What study demonstrates that HIV has been islolated from the “gut”?

  5. Truthseeker Says:

    Guadalupe M et al. Viral Suppression and Immune Restoration in the Gastrointestinal Mucosa of Human Immunodeficiency Virus Type 1-Infected Patients Initiating Therapy during Primary or Chronic Infection. J Virol. 2006 Aug; 80(16): 8236-47.

  6. Claus Says:

    ”This statement serves multiple purposes. First, you see ARV linked with the word successful. But…the virus still thrives(?). Give the public a momentary sense of hope, but keep the important paradigm-maintaining factors of medication (ARV) and an undefeatable virus in place. And in the vein of our Look Away Paradigm (thanks, Truthseeker), we need to turn our heads away from the illogic of calling something a success, when by their own admission it clearly isn’t.” (Dan)Nice observations – all of it. Still, if can read, the mother of all carrots is repeated in almost every single quote from the good doctors: ”crucial to destroying the virus””a viral reservoir that keeps us from ridding patients of the virus.””the patient will be more likely to clear the virus””preserve immune function and hasten its full recovery.”To me, ‘ridding patients of the virus’ and ‘full recovery of immune function’, sounds like other words for ‘reversible’ and ‘cure’- and not even a theoretical somewhere down the road cure, but a simple question of anti-inflammatories and some stimulation of genes that, as opposed to HIV, ‘make excellent drug targets’. Even the answer to the riddle of long time survivors can be found in this study: Those untreated HIV+ who do not progress to AIDS are constitutionally, or perhaps because of diet and life-style, less prone to inflammation in the gut. The inescapable conclusion is that we need prophylactic dispensation not of costly ARVs, but Ibuprofen and similar stuff found in anybody’s home remedy arsenal.Now the only remaining question is, was Truthseeker thus anticipated in his promised announcement of this cure because he was too fearful of unfurling his standard prematurely by saying that HIV definitely x AIDS, even when mainstrem clearly supports that it’s IG (Inflammation of the Gut) = AIDS?

  7. Michael David Says:

    Claus,Sounds good, except for the ibuprofen part. That stuff is very bad for the gut.

  8. Truthseeker Says:

    One anti-inflammatory drug group popular in treating gays has an action against the immune system so reliable it is used in transplant operations.

    Perhaps it is time to do a summary post on the cause and cure of “AIDS”, as indicated by the literature.

  9. Claus Says:

    Dr. D, TS:

    I stand corrected. There goes my Nobel Prize I guess along with with my last Ibuprofen. To tell the truth it didn’t do much for my tendonitis either (referring to the latter of the two panaceas)

  10. Glider Says:

    Although I disagree with the conclusions this researcher reached, I think looking at the gut for answers makes sense. Here’s a post (edited) that I made last November to the message board at aidsmythexposed.com. I’m curious to know what some of you think about my theory.

    *************************
    I’m exploring an idea that I’ve had for a number of years, and I was wondering if anyone here has ever investigated or considered the relationship between Leaky Gut Syndrome (LGS, aka intestinal permeability) and “HIV-related” conditions. Based on what I’ve read, it seems to me that there might be a causal connection that hasn’t been fully explored.

    Since some of you may not know what I’m referring to, let me give you a quick primer. The normal functioning of our gut depends on the presence of trillions of beneficial bacteria that live in the mucosal lining of our intestines in a symbiotic relationship with us. These bacteria help digest our food, produce vitamins such as B-12, and even protect us from harmful bacteria. But a number of factors, including the use of broad-spectrum antibiotics which kill both good and bad bacteria indiscriminately, can disrupt the natural ecology of the gut and negatively impact our health.

    One of the problems caused the by the destruction of the gut’s beneficial bacteria is LGS. This is a condition marked by increased permeability of the intestinal walls. In essense, the lining of the gut becomes sufficiently porous, albeit on a microscopic level, that stuff seeps out into the bloodstream causing the body to set off an immune response.

    Now this is where I begin to think hypothetically. Because LGS tends to get worse over time if the causes aren’t addressed, it stands to reason that as the gut becomes more and more permeable the body is forced to produce more and more antibodies as more and more stuff gets through. Is it possible that once someone develops a severe enough case of LGS they would produce antibodies of sufficient quantity and variety to trigger a positive result on the “HIV test”?

    And consider this. It’s estimated that as much as 70% of a healthy person’s t-cells are found in the mucosal lining of their gut. If someone’s intestinal walls became compromised by LGS and grew more permeable, wouldn’t you expect the body to send even more t-cells there? In other words, if a person had a case of LGS that became gradually worse wouldn’t they seem to be losing t-cells because the t-cells that are normally floating around in their bloodstream—which is where they’re measured in t-cell counting—would be increasingly deployed to the site in the body where they’re needed most?

    Also, as LGS gets worse, you’d expect the intestinal tract to become less and less efficient at doing the very thing that it’s supposed to do: absorb nutrients. So the sufferer would begin to become more and more malnourished. And isn’t malnutrition a well-known cause of immune suppression?

    Another thing to think about is that none of this would happen overnight—it probably takes many years for it to occur—creating the illusion of a “latency period.”

    **************************************

    So, there you have it—my personal theory. It offers ideas why sufferers of LGS might test HIV positive, why their t-cells would appear to be declining, why their immune system might begin to fail, and why there would appear to be a latency period. I think if you take this condition and layer on top of it other risk factors such as recreational drug abuse, you might get somewhere.

    (Below is a study I found when I was investigating my idea.)

    Cheers,

    Glider

    This study (Gut, Vol 37, 623-629, Copyright © 1995 by BMJ Publishing Group; go here: http://gut.bmjjournals.com/cgi/content/abstract/37/5/623) measured intestinal absorptive capacity and permeability in 88 “patients with HIV infection”ranging from asymptomatic, healthy individuals to those with AIDS. The conclusions reached by the authors matched remarkably well with those that I reached on my own. Here are a few highlights from the abstract:

    … “Increased intestinal permeability was found in all subgroups of patients.” [Although the study size was small, this is a remarkable finding.]

    … “Malabsorption…was prevalent in all groups of patients with AIDS but not in asymptomatic, well patients with HIV.”

    … “Malabsorption correlated significantly…with the degree of immune suppression and with body mass index.”

    … “Malabsorption and increased intestinal permeability are common in AIDS patients. Malabsorption, which has nutritional implications, relates more to immune suppression than jejunal morphological changes.”

  11. Tryptophan Bialy Says:

    Glider,

    You have hit several nails on the head and simultaneously too. However, to swtich metaphors, you neglected to throw the baby out with the dirty bath water.

    As you know so well, it has been many, many moons since the “A” in “AIDS” had any meaning and that it has been “I” for infectious since 1984. And as you also know so well, the Robin Weiss et al. proclamation in Nature that they had discovered the receptor for “the causative agent of Aids” has never been exposed to any serious challenge. This horrendous state of affairs has allowed for every single experimental finding to be reinterpreted into an unassailable thought (sic) construct in terms of a virus that puts the wiliest of Odyssean liars to everlasting shame, as your pull-quotes show so well.

    One gets so tired of saying the sky is blue and the grass is green and that AIDS without HIV quickly dissolves into a variety of very unsexy conditions like LGS or drug-induced stupidity, or an HPV infection that cannot be parlayed into grounds for lifelong disability income, and most importantly into the plethora of infections that have increasingly plagued Africa since the World Bank and its inverted development (sic) projects arrived to replace overt colonialsm in the ’80s.

    Hank had it nailed with one golden spike yesterday when he quoted the man who renamed Mapapopa (‘The Mother of All Water Falls’ in Ndembeli) Victoria for his queen and country (both puns very much intended ‘Drs’. Moore, Bennett, Smith et al.).

    We must find new lands from which we can easily obtain raw materials and at the same time exploit the cheap slave labor that is available from the natives of the colonies. The colonies would also provide a dumping ground for the surplus goods produced in our factories.

  12. Glider Says:

    Tryptophan Bialy,I feel a bit stupid admitting it, but I’m not exactly sure which baby I neglected to throw out. Will you explain again?Thanks,Glider

  13. Tryptophan Bialy Says:

    Glider,It was mostly an excuse to mix metaphors in what I imagined was an amusing manner, and was only meant to point out (ever so gently) what you already do know and mostly did in your comment,i.e. dissociate the “baby” HIV 100% from AIDS.And mostly, your instructive comment made me think of the other stuff re Africa that I have not put quite so succintly before.Na mas. Pase un buen domingo.Harvey “Dr. Tryptophan” (to my former Nigerian students) Bialy

  14. Glider Says:

    Thanks Harvey. I understand now.And in case I wasn’t clear in any way, let me say that I don’t think HIV has any role whatsoever in the development of AIDS or the condition which I think underlies much of what is called AIDS, LGS. Instead, I think LGS, once it becomes severe enough, causes you to produce antibodies of sufficient quantity and variety to consistently register false-positive on the tests.Then, I think LGS causes: the illusion of disappearing t-cells as more and more t-cells are deployed to the walls of the intestines and away from the blood; malnutrition, leading to immune suppression, as the intestinal tract becomes increasingly unable to absorb nutrients; the impression of a latency period because there is a delay of years between the time when the condition is severe enough to cause false-positive test results and the time when it worsens to the point of causing obvious illness (assuming the sufferer doesn’t address the condition).What causes LGS? Though there are many known causes, in my experience in the gay community I think the chief culprit is antibiotic overuse. Everyone’s heard the stories about guys in the late ’70s and early ’80s taking antibiotics as a precaution before going to the bathhouses. It really happened. I also knew guys who would use tetracycline before going to the pool or the beach to make their skin more sensitive to sunlight so they would tan quicker. And they would pass the bottle around to anyone who wanted them. Though I can honestly say I’ve used antibiotics only for legitimate reasons, I’ve done so far more often than I care to admit. I’ll leave the reasons to your imagination.Glider

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