Flushing out latent infection

[lydgate]

"Human immunodeficiency virus-associated dementia (HAD) encompasses a broad range of both psychiatric and neurologic symptoms. One end of the spectrum presents with minor cognitive and motor disorders (MCMDs), and at the other end is he more severe AIDS dementia complex (ADC), which is a subcortical ailment occurring at the later stages of the disease (i.e., after AIDS has developed). Although studies are less clear about the actual prevalence of dementia and/or delirium, it has been estimated that up to 20% of patients with AIDS will develop ADC and that 30% to 40% of hospitalized patients with AIDS will develop delirium (Goldenberg and Boyle, 2000b)."

From an April 2005 edition of Psychiatric Times. (The author relies quite heavily on two survey articles by Goldenberg and Boyle.)

[J220]

Not that I am not learning tons about the matter, but I thought this thread was about latent infection??

[antibody]

we know that these reservoirs are all over the body. the lymph glands, genital tract, in the intestines and they are saying some these cells can live up to 60 years.
http://www.aidsmap.com/en/news/924A65B9-5DD8-4831-824F-22D1175FDBCC.asp

[AtomicA]

I have a question about latency and the brain...

Does anyone actually know exactly what cells in the brain the virus can infect? This whole idea of clearing latency would seem to rely on infected cells being eventually killed by viral activation but if the HIV virus could infect even a few neurons then any medication that could clear them out would have to be able to clear them from every single type of cell that has latent viral DNA.

Furthermore, if it's true (as some of the studies I've been reading suggest) that the longer you have HIV the more established the latent pools become wouldn't that mean that someone who follows todays conventional wisdom of not treating with ARV's until their body needs it will be far less likely to ever have these treatments open to them if and when they become available? If the goal here is to find a cure, like a total cure, letting your latent viral pools build up over years and years of non-treatment would mean that there would be so much more to clear out than if ART was initiated at the first sign of infection.

It's something I have always had in the back of my mind since I became infected, my doctor was pretty insistant on me waiting because the drugs we have avaialble today have nasty long term consequences but if you look back 10-12 years the kinds of drugs I'm on now were nothing more than a pipe dream. 10 years from today things are probably going to be no different and I've always thought that treatment options should be weighed with the knowledge that we will always know more tomorrow than we know today. Hence why the idea of letting the virus become (perhaps) permanently established with latent viral pools seemed like insanity when there are so many people looking into the best ways to clear these pools out right now, less pools, better chance of clearing them when the technology becomes available.

just a thought, but I'd sure like to know about the brain thing. If HIV can infect neurons at all, waking up the virus and destroying those cells seems like a bad idea. Especially if the number of infected neurons increases over time. People who have had the virus for 20+ years would end up with dramatic brain damage if things like valproic acid work.

[mistertonky]

it will happen very soon..

[Esquare]

it will happen very soon..

  Care to elaborate?

[SASA39]

And what about this  ?

Statistical analysis suggests that it could take anywhere between 21 and 73
years for the reservoir to disappear completely. However, there were wide
variations between individuals in decay rates observed, and no clear correlation
between the stage of infection at which treatment commenced and the decay rate.
Several patients who started treatment in the early stages of primary infection
had detectable latently infected CD4 cells and minimal evidence of decay during
the follow-up period.
These findings call into question the view that commencing treatment during
primary infection holds the best hope of eventual HIV eradication, a position
first advocated by Dr David Ho at the 1996 Vancouver International AIDS
Conference.

[hahaha]

Finally, using our latent cell lines, we identified six drugs (of 16,000 tested) that reactivate latent HIV. Such drugs could be used in patients to flush out their latently infected cells and eliminate latent pools (flushing hypothesis). If successful, this strategy could form the basis for a therapy to eradicate HIV infection in patients.

Wouldn's that be perfect if:
1.  Place patient on Harrt --> reduce the virus to undetectable
2 inject PD-1 --> CD-8 knows how to fight infected CD4
3 inject Emory Vaccine --> create antibody
4 take the "flushing" med and inject PD-1 again-->let latented cell present, then Haart, PD-1 and Vaccine can co-work to kill the remaining virus
5 then stop the fxxking damned Haart!!!

Oh, I cross my finger and wish the whole process can come true the coming year!!

[NYCguy]

Atomic, this brain thing keeps me awake nights too (Ambien helps, fortunately).  I'm still adjusting to the fact that I had something in my body that I have to take pills for every day or it will kill me, let alone that idea that I might start losing my mind in a decade or so.  However, everything I have read says that neurons are NOT infected by HIV.  I don't know if this has been proven, but i have definitely read it.  The problem is that hiv passes through the blood-brain barrier and infects some kind of cells in the brain which it is hard for the meds to touch (as it does in the balls as well, but those cells are quite as important as brain cells...).  That's all I know.  I do worry that all these new treatments still won't get those last cells in the brain, but who knows.  However, I have definitely read that neurons aren't affected, but comments on this would be appreciated.

[NYCguy]

this is from 2005, but interesting research about the brain and hiv dementia re above discussion:

http://www.nsf.gov/news/news_summ.jsp?cntn_id=104479&org=OLPA

White blood cells may be cause of dementia in people with AIDS


September 27, 2005


Researchers studying the evolution of the human immunodeficiency virus (HIV) in the brain have found that the body's own defenses may cause HIV-related dementia.

Publishing in the Sept. 2005 issue of the Journal of Virology, the researchers show that HIV in the temporal lobe mutates at a rate 100 times faster than in other parts of the body, triggering white blood cells to continually swarm to attack the infection.  The associated overcrowding and inflammation appear to cause the dementia.

Earlier studies had suggested that the build-up of white blood cells could lead to HIV-related dementia, but this is the first study to track the probable mechanism.

The findings could lead to new treatments that target HIV-infected white blood cells, perhaps one day countering the brain wasting that will affect as many as 15 percent of the nearly 40 million people around the world who are infected with the virus.

The study is a collaboration among researchers at the University of California at Irvine, the University of Florida at Gainesville, Gene Johnson, Inc., of St. Augustine, Fla., the University of California at San Francisco (UCSF) and the University of Oxford in the United Kingdom.

One of the critical tools behind the discovery is HIVBase, a genetic data-storage and -analysis tool with which the researchers tracked the rapidly evolving viruses.  Gene Johnson developed the tool with the support of an NSF Small Business Innovation Research award.

According to co-author Susanna Lamers of Gene Johnson and UCSF, the results strengthen an earlier hypothesis by Kenneth Williams of Harvard University and William Hickey of Dartmouth Medical School.  They had suggested that the continual build-up of white blood cells in the brain could lead to HIV-associated dementia.

"In our work," says Lamers, "we conducted a thorough examination of HIV genetic sequences and were able to prove that the researchers’ concept was a good explanation for both clinical latency—when the body mounts a strong immune defense and the number of viral particles decreases—and the long-term damage associated with HIV infection in the brain.  They offered the model, we provided strong evidence that the model is accurate."

Additional information is available in press releases from the University of Florida and Gene Johnson.

-NSF-



Media Contacts
Joshua A. Chamot, NSF (703) 292-7730 jchamot@nsf.gov
April Frawley Birdwell, University of Florida Health Science Center (352) 273-5817 afrawley@vpha.health.ufl.edu
Jeff Sheehy, University of California, San Francisco, AIDS Research Institute (415) 597-8165 JSheehy@ari.ucsf.edu


Program Contacts
Errol B. Arkilic, NSF (703) 292-8095 earkilic@nsf.gov


Principal Investigators
Susanna Lamers, Gene Johnson, Inc. and the University of California, San Francisco (985) 493-3487 susanna@genejohnson.net


Related Websites
Gene Johnson, Inc. Press Release: http://www.hivbase.com
University of Florida Press Release: http://www.news.health.ufl.edu/story.asp?ID=2097