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Author Topic: Low cholesterol tied to slow progression of HIV  (Read 1333 times)

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Offline Skydrake

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Low cholesterol tied to slow progression of HIV
« on: May 16, 2014, 01:28:10 PM »
Low cholesterol in immune cells tied to slow progression of HIV

People infected with HIV whose immune cells have low cholesterol levels experience much slower disease progression, even without medication, according to University of Pittsburgh Graduate School of Public Health research that could lead to new strategies to control infection.

 
The Pitt Public Health researchers found that low cholesterol in certain cells, which is likely an inherited trait, affects the ability of the body to transmit the virus to other cells. The discovery, funded by the National Institutes of Health (NIH), is featured in today's issue of mBio, the journal of the American Society for Microbiology.
When HIV enters the body, it is typically picked up by immune system cells called dendritic cells, which recognize foreign agents and transport the virus to lymph nodes where it is passed to other immune system cells, including T cells. HIV then uses T cells as its main site of replication. It is through this mechanism that levels of HIV increase and overwhelm the immune system, leading to AIDS. Once a person develops AIDS, the body can no longer fight infections and cancers. Prior to effective drug therapy, the person died within one to two years after the AIDS diagnosis.
"We've known for two decades that some people don't have the dramatic loss in their T cells and progression to AIDS that you'd expect without drug therapy," said lead author Giovanna Rappocciolo, Ph.D., an assistant professor at Pitt Public Health. "Instead the disease is much slower to progress, and we believe low cholesterol in dendritic cells may be a reason."
The discovery was made possible by using 30 years of data and biologic specimens collected through the Pitt Men's Study, a confidential research study of the natural history of HIV/AIDS, part of the national NIH-funded Multicenter AIDS Cohort Study (MACS).
"We couldn't have made this discovery without the MACS. Results like ours are the real pay-off of the past three decades of meticulous data and specimen collection," said senior author Charles Rinaldo, Ph.D., chairman of Pitt Public Health's Department of Infectious Diseases and Microbiology, and professor of pathology. "It is thanks to our dedicated volunteer participants that we are making such important advances in understanding HIV, and applying it to preventing and treating AIDS."
Medications called combination antiretroviral therapy (ART) disrupt the viral replication process and can delay the onset of AIDS by decades.
However, even without taking ART, a small percentage of people infected with HIV do not have the persistent loss of T cells and increase in levels of HIV after initial infection. They can sometimes go many years, even more than a decade, without the virus seriously compromising the immune system or leading to AIDS.
Through the Pitt Men's Study/MACS, eight such "nonprogressors" were assessed twice a year for an average of 11 years and compared to eight typically progressing HIV-positive counterparts.
Dr. Rappocciolo and her colleagues found that in nonprogressors, the dendritic cells were not transferring the virus to T cells at detectible levels. When taking a closer look at these dendritic cells, the researchers discovered that the cells had low levels of cholesterol, even though the nonprogressors had regular levels of cholesterol in their blood. A similar finding was shown for B lymphocytes, which also pass HIV to T cells, leading to high rates of HIV replication.
Cholesterol is an essential component of the outer membranes of cells. It is required for HIV to replicate efficiently in different types of cells. None of the study participants were taking statins, which are cholesterol-lowering medications that some people take to prevent vascular problems when cholesterol in their blood is too high.
When HIV was directly mixed with the nonprogressors' T cells in the laboratory, those T cells became infected with the virus at the same rate as the T cells of the regularly progressing, HIV-positive participants. Indeed, T cells from the nonprogressors had normal levels of cholesterol.
"This means that the disruption is unlikely to be due to a problem with the T cells, further supporting our conclusion that the slow progression is linked to low cholesterol in the dendritic cells and B cells," said Dr. Rappocciolo.
"What is most intriguing is that dendritic cells in the nonprogressors had this protective trait years before they became infected with HIV," Dr. Rinaldo said. "This strongly suggests that the inability of their dendritic cells and B cells to pass HIV to their T cells is a protective trait genetically inherited by a small percentage of people. Understanding how this works could be an important clue in developing new approaches to prevent progression of HIV infection."

Story source:
http://www.sciencedaily.com/releases/2014/04/140429085558.htm

Study source:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010827/
http://mbio.asm.org/content/5/3/e01031-13

Offline Mishma

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    • Marquis de Vauban
Re: Low cholesterol tied to slow progression of HIV
« Reply #1 on: May 26, 2014, 08:35:45 PM »
Since this focused on individuals who genetically produced (or absorbed) less cholesterol and as a result had lower levels of circulating cholesterol it begs the question: Can diet/exercise induce the same protective effect?

I know my own total cholesterol dropped over 100 when I switched to a integrase inhibitor, although my LDL is still greater than my HDL. And this is after abandoning the Statins.
2016 CD4 25% UD (less than 20). 27+ years positive. Isentress, Truvada, Acyclovir, Clonazepam, Zolpidem, Bupropion, Lisinopril, Pravastatin, Quetiapine, Doxcycline, Testosterone, Suatriptan/Naproxen, Restasis, Dorzolamide, Latanoprost, Asprin, lortab, Levothyroxine, Fioricet, Restasis, Triamclinolone, Nitrostat.

Offline Skydrake

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Re: Low cholesterol tied to slow progression of HIV
« Reply #2 on: June 01, 2014, 02:51:37 PM »
The role of choresterol can be also positive.
Especially without therapy HIV+ people with genetic hypocholesterolemia have an much higher mortality than those with hypercholesterolemia:
http://journals.lww.com/aidsonline/Citation/1997/07000/Low_serum_cholesterol_and_risk_of_death_from_AIDS.14.aspx

But even in HIV- individuals hypocholesterolemia is related to various diseases. Too low cholesterol can be worse than too much.
http://www.ravnskov.nu/the%20benefits%20of%20high%20C.htm

Since this focused on individuals who genetically produced (or absorbed) less cholesterol and as a result had lower levels of circulating cholesterol it begs the question: Can diet/exercise induce the same protective effect?

Probably diets and exercises have a protective effect "in se",  independently to the resulting level of the choresterol.

Also cholesterol lowering drugs can help aganist hiv :
http://aids.about.com/b/2011/02/25/cholesterol-lowering-drugs-may-slow-hiv-progression.htm

« Last Edit: June 01, 2014, 02:55:43 PM by Skydrake »

Offline Mishma

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    • Marquis de Vauban
Re: Low cholesterol tied to slow progression of HIV
« Reply #3 on: June 01, 2014, 06:49:56 PM »
Despite having CVD, one widow maker and one DVT I was willing to go on Statins for it's supposed anti-inflammatory properties. This is nothing new as years ago quite competent physicians were prescribing it prophylactically for all sorts of conditions-with inflammation in mind.  The untoward effects is what got me to quit.

Same with the Doxycycline I took for awhile for my eyes, however I decided that the risk of staying on antibiotics for life was greater than what the cyclosporin drops were   doing.

Same with the quinoline drugs they were using with us for rheumatic HIV muscle issues. They're toxic as hell on nerves. Likewise I bagged them after a time.

HIV is not my problem. It is the auto-immune issues due to my chronic inflammatory state due to my HIV.

My understanding with respect to cholesterol isn't the too high too low aspect but rather the LDL/HDL ratio. Much like our inverted CD4/CD8 ratio is predictive to some extent of other issues.
2016 CD4 25% UD (less than 20). 27+ years positive. Isentress, Truvada, Acyclovir, Clonazepam, Zolpidem, Bupropion, Lisinopril, Pravastatin, Quetiapine, Doxcycline, Testosterone, Suatriptan/Naproxen, Restasis, Dorzolamide, Latanoprost, Asprin, lortab, Levothyroxine, Fioricet, Restasis, Triamclinolone, Nitrostat.

Offline Skydrake

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  • Posts: 41
Re: Low cholesterol tied to slow progression of HIV
« Reply #4 on: June 02, 2014, 11:36:39 AM »
There are several kinds of statins. According my phisician, it's difficult to foresee the exact personal reaction. In my case he has just prescribed me only red yeast rice instead statins, in order to avoid every potential interraction with the liver (I'm HCV+, also).
At least I have no chronic inflammation (my CD4/CD8 ratio is 1.1).

In the last days some studies have been published about chronic infiammatory state and microbial translocation:
Studies:
http://www.jci.org/articles/view/75090
http://m.jid.oxfordjournals.org/content/early/2014/05/25/infdis.jiu305.abstract
Divulgative article:
http://medicalxpress.com/news/2014-05-breakthrough-hivaids-drug-therapy.html

Offline tryingtostay

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  • Posts: 273
Re: Low cholesterol tied to slow progression of HIV
« Reply #5 on: June 02, 2014, 07:37:56 PM »
In the last days some studies have been published about chronic infiammatory state and microbial translocation:
Studies:
http://www.jci.org/articles/view/75090
http://m.jid.oxfordjournals.org/content/early/2014/05/25/infdis.jiu305.abstract
Divulgative article:
http://medicalxpress.com/news/2014-05-breakthrough-hivaids-drug-therapy.html


The second link seems to contradict what first link is saying, or am I reading it wrong?

Offline Skydrake

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  • Posts: 41
Re: Low cholesterol tied to slow progression of HIV
« Reply #6 on: June 03, 2014, 09:14:01 AM »

The second link seems to contradict what first link is saying, or am I reading it wrong?

It seems this drug, sevelamer, works well in macaques (1°study), but less in patients receiving hemodialysis (2°study)...
After all, it is only one of the proposed therapies against microbial translocation and resulting chronic inflammation.

Offline tryingtostay

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  • Posts: 273
Re: Low cholesterol tied to slow progression of HIV
« Reply #7 on: June 03, 2014, 09:32:43 AM »
It seems this drug, sevelamer, works well in macaques (1°study), but less in patients receiving hemodialysis (2°study)...
After all, it is only one of the proposed therapies against microbial translocation and resulting chronic inflammation.

What other proposed therapies are being looked into?

Offline Skydrake

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  • Posts: 41
Re: Low cholesterol tied to slow progression of HIV
« Reply #8 on: June 03, 2014, 02:32:57 PM »
What other proposed therapies are being looked into?

They proposed everything.
Pro-biotics, pre-biotics, diets, vitamin D, drugs agaisnt irritation by other drugs.
Even the astonishing "fecal transplant".

I only used, and I use, kefir.

Offline tryingtostay

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  • Posts: 273
Re: Low cholesterol tied to slow progression of HIV
« Reply #9 on: June 03, 2014, 03:24:19 PM »
So this sevelamer is by far the best they've got, and it works?

Offline Skydrake

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  • Posts: 41
Re: Low cholesterol tied to slow progression of HIV
« Reply #10 on: June 04, 2014, 04:44:58 AM »
So this sevelamer is by far the best they've got, and it works?
I think there is no magic pill.
The microbial traslocation in the gut is a consequence of several reasons.
Most people have to assume only vitamin D (very useful also for bones and as antioxidant).
If the origin of the irritation is a drug as lopinavir or ritonavir, it's useful Crofelemer.
The fecal transplant only for a very few people with patologic microbials in the flora of the gut, as clostridium difficile.
 
For all the rest, a more equilibrate and healthy diet is enough.
Obviolusly, the microbial traslocation is only one of the possible reasons of the chronic inflammation.

 


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