HIV Research Advance

Okay, admittedly, I may be a bit of a research geek, but this is pretty interesting stuff. It looks like modern HIV treatments can clear the body of virus in the blood, but not in the gut. Perhaps a cure is as near as clearing both?

In any case, as with cancer, we once again see a direct link between inflammatory issues and the ability of a disease to get started or hang on. While inflammation has its purpose, it makes you wonder.

UC Davis study finds HIV hiding from drugs in gut, preventing immune recovery

(Sacramento, Calif.) – 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. Results of the three-year study appear in the August issue of the Journal of Virology ( available online today at http://jvi.asm.org/ ).

“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.”

That’s a stunning revelation.

It’s amazing, Western Medicine, when you think about it. We just found out about this disease 25 years ago, and people with HIV are now close to living out there lifespan as normally as possible in many cases.

Too bad they don’t put as much time and money into Chronic Hepatitis C research. Four times as many are infected with it as compared to HIV. I guess AIDS has a better PR department.

Here are some statistics:

CHC STATISTICS vs. AIDS STATISTICS

Numbers of People Infected:
3.5 million persons in the United States suffer from CHC ( Chonic Hepatitis C )
700,000 persons in the United States infected with HIV
400 million worldwide with CHC
20 million worldwide with HIV
1 in every 15 people in the world suffers from CHC

Numbers of New Cases Each Year
150,000 new cases of CHC in the US
40,000 new cases of HIV

Numbers of People who will Die
80 million worldwide from CHC
20 million worldwide from AIDS
4 times as many deaths worldwide from CHC as from AIDS.

NIH Funding for Research for CHC vs. AIDS
$1.15 billion per year on AIDS from 1991-1995
$4.5 million per year on CHC
.5 billion per year on treatment/support for AIDS (Ryan White Act)
$0 funding for treatment/support for CHC
$1.65 billion yearly on AIDS<
$4.5 million per year on CHC
366 times more on AIDS than CHC

It is the most common, undiagnosed infectious disease. At least a third of the people infected don’t know they have it. And don’t expect your doctor to find it during a routine annual physical. He has to order a specific blood test for it.

Don’t think you may have it? Were you ever vaccinated as a child? Received a blood transfusion? Gotten a tattoo? Sexual transmission is also possible, but rare.

Many people who have it don’t know how they got it. And it doesn’t help that it is surrounded by the stigma of being a drunky/junky disease.

There is no cure, but there is treatment (which may be worse than the disease itself, and may or may not be effective): Forty-eight weeks of weekly Pegylated Interferon injections which may or may not be covered by your insurance.

[quote]gojira wrote:
Too bad they don’t put as much time and money into Chronic Hepatitis C research. Four times as many are infected with it as compared to HIV. I guess AIDS has a better PR department.
[/quote]

I know it doesn’t help people “right now”, but I’m pretty sure that there will be a lot of carry over into many aspects of virology and other areas.

Perhaps they had better hurry up and cure AIDS so these other issues can get the attention they may require or deserve.

[quote]gojira wrote:

All sorts of stuff
[/quote]

Whoa. Thank you for that gojira, I gotta admit to being completely ignorant about how widespread Hep C is.

[quote]vroom wrote:
gojira wrote:
Too bad they don’t put as much time and money into Chronic Hepatitis C research. Four times as many are infected with it as compared to HIV. I guess AIDS has a better PR department.

I know it doesn’t help people “right now”, but I’m pretty sure that there will be a lot of carry over into many aspects of virology and other areas.

Perhaps they had better hurry up and cure AIDS so these other issues can get the attention they may require or deserve.[/quote]

“Squeaky wheel gets the grease”.

Apparently they have looked at some of the stategies used for the HIV and have tried to apply them to the HCV, but the two viruses behave differently. Ironically, many folks who are HIV positive are also HCV positive.

[quote]gojira wrote:
Apparently they have looked at some of the stategies used for the HIV and have tried to apply them to the HCV, but the two viruses behave differently. Ironically, many folks who are HIV positive are also HCV positive.[/quote]

Yeah, I know, but there have been a lot of new advances in viral research.

While the treatment efforts may not carry over, I suspect the research capabilities will. At least when they aren’t being focused on other efforts. There are a good number of viruses that could use a bit of attention.

Can you imagine how much progress could be made in research on cancer, AIDS, Hep C, etc. if so much money wasn’t spent on the space program or wars?

[quote]vroom wrote:
gojira wrote:
Apparently they have looked at some of the stategies used for the HIV and have tried to apply them to the HCV, but the two viruses behave differently. Ironically, many folks who are HIV positive are also HCV positive.

Yeah, I know, but there have been a lot of new advances in viral research.

While the treatment efforts may not carry over, I suspect the research capabilities will. At least when they aren’t being focused on other efforts. There are a good number of viruses that could use a bit of attention.[/quote]

Currently the best hope is using RNA interferance (RNAi). This will work on all RNA based viruses (which is HIV, HEPs and pretty much all of the bad stuff). RNAi has the potental to be a full cure. Too complex to get into in a post but if your interested in virology or genetics in general, you may find this interesting. Wiki has a decent overview.

The real battle of HIV infection begins in the gut?

Sorely tempted to make an obligatory gay oral sex joke here, but I shall refrain.

Fascinating.

[quote]gojira wrote:
Too bad they don’t put as much time and money into Chronic Hepatitis C research.
[/quote]

With interferon/Ribavirin treatment, we are curing about 60% of those treated. The treatment is ugly. Interferon is made by the body to prevent viral propogation. It is the stuff that gives you those lovely feelings of fatigue, bodyaches etc. when you have the flu. Severe depression, anemia are a couple of other side effects. People still get through the treatments, and for good reason.

There are some new drugs in phase 3 trials which I am told are more promising that the current therapy. My guess is that in the next 10 years the cure rate (CURE RATE, not control…CURE) will approach 100%. It isn’t that there isn’t money/research going into HCV research, it is that the media doesn’t put it out there because the public doesn’t want to hear about it.

[quote]teratos wrote:
gojira wrote:
Too bad they don’t put as much time and money into Chronic Hepatitis C research.

With interferon/Ribavirin treatment, we are curing about 60% of those treated. The treatment is ugly. Interferon is made by the body to prevent viral propogation. It is the stuff that gives you those lovely feelings of fatigue, bodyaches etc. when you have the flu. Severe depression, anemia are a couple of other side effects. People still get through the treatments, and for good reason.

There are some new drugs in phase 3 trials which I am told are more promising that the current therapy. My guess is that in the next 10 years the cure rate (CURE RATE, not control…CURE) will approach 100%. It isn’t that there isn’t money/research going into HCV research, it is that the media doesn’t put it out there because the public doesn’t want to hear about it.

[/quote]

Unfortunately CHC is still surrounded by the stigma of being a drunky/junky disease which is why the majority of people that know they have it don’t talk about it.

[quote]gojira wrote:
Too bad they don’t put as much time and money into Chronic Hepatitis C research. Four times as many are infected with it as compared to HIV. I guess AIDS has a better PR department.[/quote]

Don’t get me wrong, CHC is a horrible disease, but at least they have cures for it.

One very troublesome thing about HC is the resiliency of the virus outside the body. The actions of HIV inside the body, however, seem more complicated and would present more research challenges.

[quote]Reef wrote:
Can you imagine how much progress could be made in research on cancer, AIDS, Hep C, etc. if so much money wasn’t spent on the space program or wars?[/quote]

Yeah, talk about a PR department. NASA is king. Can’t say the same for their technicians. You mean kilograms and lbs plugged in for calculations don’t work interchangeably? Cough, cough

[quote]simon-hecubus wrote:
gojira wrote:
Too bad they don’t put as much time and money into Chronic Hepatitis C research. Four times as many are infected with it as compared to HIV. I guess AIDS has a better PR department.

Don’t get me wrong, CHC is a horrible disease, but at least they have cures for it.

One very troublesome thing about HC is the resiliency of the virus outside the body. The actions of HIV inside the body, however, seem more complicated and would present more research challenges.
[/quote]

There is no cure, only treatments at this time. The current treatment referenced above is only effective for 60% of the population infected with the genotype 1 (most common genotype in US). Many people would go through the treatment relapse and have to treat again. Others choose not to go through treatment at all, and wait patiently for better options 4 or 5 years down the road. Many of these folks get scammed by folks promising a cure with herbal or other miracle treatments (just as cancer patients do). While there are some herbal supps (such as Milk Thistle) that have a lot of anecdotal support regarding promoting liver health, if there was a cure we would have heard about it on the news.

[quote]gojira wrote:
There is no cure, only treatments at this time. The current treatment referenced above is only effective for 60% of the population infected with the genotype 1 (most common genotype in US)…if there was a cure we would have heard about it on the news.[/quote]

What about these people I keep hearing who have been virus-free for 5+ years? I personally know someone who’s been virus free for 3 years. There’s other survivors who have a weekly radio show here in Houston.

My friend and these others went through the 12-18 month drug treatment. No herbal crap. That’s a finite treatment regimen, as opposed to lifelong suppression like HIV treatments.

The milk thistle, while no cure, will help an overworked liver do its job detoxifying the body.

[quote]simon-hecubus wrote:
gojira wrote:
Too bad they don’t put as much time and money into Chronic Hepatitis C research. Four times as many are infected with it as compared to HIV. I guess AIDS has a better PR department.

Don’t get me wrong, CHC is a horrible disease, but at least they have cures for it.

One very troublesome thing about HC is the resiliency of the virus outside the body. The actions of HIV inside the body, however, seem more complicated and would present more research challenges.
[/quote]

At least we’re actually making progress in curing something, ANYTHING. I keep seeing those AIDS-awareness bus ads in my and I wonder if I’m not going to see those ads anymore (for a good reason) in a couple of years. Thanks for the update, Vroom.