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Author Topic: When does the latent HIV reservoir form?  (Read 8171 times)

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Offline hotpuppy

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When does the latent HIV reservoir form?
« on: December 15, 2009, 10:21:24 pm »
I was trying to find some clinical evidence of when the latent reservoir of HIV forms in the course of infection.

Does anyone remember seeing something concrete somewhere?

I'm looking for something scientific, credible, and recent.  Preferably a study with statistical data.
Don't obsess over the wrong things.  Life isn't about your numbers, it isn't about this forum, it isn't about someone's opinion.  It's about getting out there and enjoying it.   I am a person with HIV - not the other way around.

Offline hotpuppy

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Re: When does the latent HIV reservoir form?
« Reply #1 on: December 17, 2009, 11:04:04 pm »
bump.....

was hoping someone had seen good data on this.
Don't obsess over the wrong things.  Life isn't about your numbers, it isn't about this forum, it isn't about someone's opinion.  It's about getting out there and enjoying it.   I am a person with HIV - not the other way around.

Offline Inchlingblue

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Re: When does the latent HIV reservoir form?
« Reply #2 on: December 17, 2009, 11:43:54 pm »
Reservoirs begin to form when the virus infects activated T cells that can enter the resting state. This happens very soon after initial infection with HIV, which is the reason that if someone is going to use PEP it should be initiated within 2–24 hours (and no later than 48–72 hours) of possible exposure to HIV, and must continue for approximately four weeks.

Once established the reservoirs can then become larger and more varied over time. There was a recent study that looked at HIV reservoir size and persistence, below.

LINK:

http://www.natap.org/2009/HIV/062609_01.htm

Latent HIV Reservoir Develops Early in Activated T Cells

A report in the Journal of Virology (2000;74:7824-7833) reveals that latent HIV reservoirs form when the virus infects activated T cells that can enter a resting state. Dr. Robert Siliciano of Johns Hopkins University School of Medicine reports that the latent HIV reservoir stems from R5 viruses, which do not enter resting T cells. The authors believe that the latent reservoir continues to infect other cells that also become resting cells. (Reuters Health Information Services (www.reutershealth.com) (09/26/00))


LINK:

http://www.thebody.com/content/art30635.html
« Last Edit: December 18, 2009, 03:58:29 pm by Inchlingblue »

Offline Carly

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Re: When does the latent HIV reservoir form?
« Reply #3 on: December 18, 2009, 09:57:28 am »
So, the reservoir cells are the ones that are essentially preventing a "cure" for HIV, correct?  They're the ones that even the new meds can't get to?  If there was someway we could get to the reservoir cells & destroy them, then HIV would be cured, is that correct?

Sorry, I'm just confused over all this & I'm trying to get it sorted out so I know what the hell I'm talking about when I try to explain it to other people.

Offline Inchlingblue

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Re: When does the latent HIV reservoir form?
« Reply #4 on: December 18, 2009, 10:10:32 am »
So, the reservoir cells are the ones that are essentially preventing a "cure" for HIV, correct?  They're the ones that even the new meds can't get to?  If there was someway we could get to the reservoir cells & destroy them, then HIV would be cured, is that correct?


Yeah, that's basically correct. The existing ARV medications have no way of reaching the reservoirs. It's been estimated that 99+% of virus is killed off with effective HAART, so we're talking only less than 1% that we have no way of reaching right now! More specifically, the number of resting memory Tcells infected with latent HIV capable of reproducing if HAART is stopped is very, very small: 0.0001%, or one out of every million! If ARV meds are stopped that's enough for them to come back full force.

There are some promising studies looking at ways to reach the virus in the reservoirs, especially those being conducted by Dr. Siciliano at Johns Hopkins.

LINK:

http://forums.poz.com/index.php?topic=29205.0

This is also very promising:

http://forums.poz.com/index.php?topic=27421.0
« Last Edit: December 18, 2009, 10:14:14 am by Inchlingblue »

Offline Carly

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Re: When does the latent HIV reservoir form?
« Reply #5 on: December 18, 2009, 05:37:46 pm »
Yeah, that's basically correct. The existing ARV medications have no way of reaching the reservoirs. It's been estimated that 99+% of virus is killed off with effective HAART, so we're talking only less than 1% that we have no way of reaching right now! More specifically, the number of resting memory Tcells infected with latent HIV capable of reproducing if HAART is stopped is very, very small: 0.0001%, or one out of every million! If ARV meds are stopped that's enough for them to come back full force.

There are some promising studies looking at ways to reach the virus in the reservoirs, especially those being conducted by Dr. Siciliano at Johns Hopkins.

LINK:

http://forums.poz.com/index.php?topic=29205.0

This is also very promising:

http://forums.poz.com/index.php?topic=27421.0

That is absolutely amazing.  Until my boyfriend tested positive & I had to start educating myself, I had no idea we were this far along in the treatment for HIV.  I knew it was a chronic disease, but I thought people still had to take those dreaded "AIDS cocktails" that you always heard about on tv.  How far we have come!  And hopefully things will continue to improve in the future, but I won't get my hopes up.  I know HIV is a tricky, tricky little virus.  I can understand why some people think the virus is some sort of government conspiracy, as the way it works makes it almost seem like it was created by some sort of evil cackling comic book villan/mad scientist in his underground lab.

But I do think the only direction we can go in now as far as treatment for HIV is concerned is up.  However, I realize that if a drug is ever found that would cure HIV, the pharmaceutical companies will probably charge every one $18734801734731247230178321.00 for it.  I think it's more than a coincidence that the life saving drugs are usually the most expensive.  And that's not just medications for HIV.  The medication my grandfather takes every day to keep him from going into complete heart failure is $100 per pill, which would equal out to about $3000 a month.  Fortunately he has VA insurance (a government-run system, I might add) to pay for it.  But I suppose that's for a different thread.

Offline Inchlingblue

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Re: When does the latent HIV reservoir form?
« Reply #6 on: December 18, 2009, 06:37:16 pm »
I knew it was a chronic disease, but I thought people still had to take those dreaded "AIDS cocktails" that you always heard about on tv.  


The term "cocktail" came about when it was discovered that taking three (ideally) different medications is what could stop the virus from mutating and developing resistance, hence it's a "cocktail" of meds.

What everyone takes now is still considered a "cocktail" since it usually involves three different meds, they're just much easier to take than the early versions, generally less toxic and with fewer side effects.

There are exceptions to the cocktail, some people are able to take Kaletra monotherapy (which is technically two meds anyway so I guess it's still a cocktail). So far, there is not just one med that will do the trick.
« Last Edit: December 18, 2009, 06:45:01 pm by Inchlingblue »

Offline Carly

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Re: When does the latent HIV reservoir form?
« Reply #7 on: December 18, 2009, 06:44:35 pm »
The term "cocktail" came about when it was discovered that taking three (ideally) different medications is what could stop the virus from mutating and developing resistance, hence it's a "cocktail."

What everyone takes now is still considered a "cocktail" since it usually involves three different meds, they're just much easier to take than the early versions, generally less toxic and with fewer side effects. There are exceptions, some people are able to take Kaletra monotherapy (which is technically two meds anyway).

I did not know that.  I always pictured a "cocktail" as something consisting of at least 10 different extremely toxic pills that did nothing but prolong the inevitable.  So have people always had to take just 3 different meds?  Or is that something that has just came about in the last 10 to 15 years?

Offline Inchlingblue

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Re: When does the latent HIV reservoir form?
« Reply #8 on: December 18, 2009, 07:00:47 pm »
I did not know that.  I always pictured a "cocktail" as something consisting of at least 10 different extremely toxic pills that did nothing but prolong the inevitable.  So have people always had to take just 3 different meds?  Or is that something that has just came about in the last 10 to 15 years?

Sent you a PM so we don't hijack the thread.

Offline hotpuppy

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Re: When does the latent HIV reservoir form?
« Reply #9 on: December 23, 2009, 09:13:00 am »
I don't mind the side conversation.....

Although I would like to suggest that "cocktail" does not have to be 3 meds.  It can be 2.  I was in a study for 18 months with a PI and a Entry Inhibitor boosted by another PI.  It worked extremely well.... other than some liver toxicity ... but we don't know which med caused that.

My point being that multiple drugs work.

I have a WAG (Wild Ass Guess) that we will see HAART to undetectable for say 6 months followed by maintenance therapy with a EI.  I'm not a doc, I didn't stay at a Holiday Inn Express last night.... and have nothing beyond my own experience and knowledge to backup that statement.

However, my own experience is that the drugs got my viral load to undetectable quickly and kept it there for 18 months.  When I stopped meds we expected my viral load to rebound.  They did bloodwork 10 days later and the VL was undetectable still. 

No idea how long it will stay that way, so I'm trying to learn about the viral reservoir.

What I have concluded so far is that your immune memory stems from the T-cells that are inactive.  When a new infection occurs they "wake up" and fight it.  If HIV is hiding in one of the sleeping cells it then comes to life when the cell does.  Starting it's replication process all over again.
Don't obsess over the wrong things.  Life isn't about your numbers, it isn't about this forum, it isn't about someone's opinion.  It's about getting out there and enjoying it.   I am a person with HIV - not the other way around.

Offline Inchlingblue

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Re: When does the latent HIV reservoir form?
« Reply #10 on: December 23, 2009, 10:24:41 am »
Although I would like to suggest that "cocktail" does not have to be 3 meds.  It can be 2.  I was in a study for 18 months with a PI and a Entry Inhibitor boosted by another PI.  It worked extremely well.... other than some liver toxicity ... but we don't know which med caused that.
 

I'm hoping that Isentress and Reyataz get approved as a combo because there were some small non-randomized studies where it was shown to work (Reyataz raises the levels of Isentress). This would involve only two drugs, both of which are pretty good ones. Even though the term "drug cocktail" or "multi-drug" cocktail usually means three or more I guess anything more than one drug can be considered a "cocktail." 

Your WAG about EI monotherapy isn't far fetched, IMHO. Once undetectable for a while it seems to be easier to control the virus, as opposed to when it's actively replicating and detectable.
« Last Edit: December 23, 2009, 10:41:09 am by Inchlingblue »

Offline aztecan

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Re: When does the latent HIV reservoir form?
« Reply #11 on: December 23, 2009, 11:44:51 am »

However, my own experience is that the drugs got my viral load to undetectable quickly and kept it there for 18 months.  When I stopped meds we expected my viral load to rebound.  They did bloodwork 10 days later and the VL was undetectable still.  

No idea how long it will stay that way, so I'm trying to learn about the viral reservoir.

What I have concluded so far is that your immune memory stems from the T-cells that are inactive.  When a new infection occurs they "wake up" and fight it.  If HIV is hiding in one of the sleeping cells it then comes to life when the cell does.  Starting it's replication process all over again.

How long you remain undetectable will vary based on your immune system, on the strength of the virus with which you were infected and your overall general health.

I know people who stopped meds after prolonged use of ARVs and did not show a viral load for a few months. Then it popped up.

One of the largest reservoirs for HIV is in your gut, because that is where a major percentage of your immune system focuses.

Source:   http://www.poz.com/articles/761_7786.shtml

This makes sense, since that is where a large proportion of the foreign organisms gain entry to the body.

Anyway, that is most likely where people see a viral load resurgence coming from. I remember years ago, there was a theory that HIV lay dormant in cells, like you mentioned. But I think that now has changed to the belief that the ongoing reservoirs in other areas, like the gut, the central nervous system and the brain, and even the lymphatic system, is probably what feeds new life into the viral load of those who go off meds.

As I believe someone else mentioned, these reservoirs form almost immediately during the early days of infection when the virus is reproducing unhampered by the body's defenses.

Regarding the entry inhibitors, my doctor and I spoke of them a little while ago and there are issues involving the efficacy of those types of treatments in the general population and the ability of the virus to mutate and, thereby get around that particular type of therapy.

I haven't read up enough on it yet. but I do remember the doctor telling me about it.

I am always hopeful, though. I was one of those who took the early "cocktails." My first regimen consisted of 17 pills a day.

Things are certainly much better today and, I hope, they will continue to improve as the years pass.

HUGS,

Mark

Edited to improve my poor semantics.
« Last Edit: December 23, 2009, 11:52:54 am by aztecan »
"May your life preach more loudly than your lips."
~ William Ellery Channing (Unitarian Minister)

Offline hotpuppy

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Re: When does the latent HIV reservoir form?
« Reply #12 on: December 24, 2009, 04:52:32 pm »
Well, I found out from my doc that my labwork from last Monday had a Viral load of 60.  Not the end of the World, but not undetectable. 

Entry Inihibitors (EI's) do not work for everyone, but for about 60% of those infected by HIV they will work.  About 60% of the population is R5 tropism.  It is thought that the virus can switch, but not well understood.

When the time is right to start meds again I plan on discussing EI's with my doctor.  Our last discussion was to continue using what worked.
Don't obsess over the wrong things.  Life isn't about your numbers, it isn't about this forum, it isn't about someone's opinion.  It's about getting out there and enjoying it.   I am a person with HIV - not the other way around.

Offline john33

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Re: When does the latent HIV reservoir form?
« Reply #13 on: December 24, 2009, 06:56:21 pm »
what is R5 tropism?

Offline Inchlingblue

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Re: When does the latent HIV reservoir form?
« Reply #14 on: December 24, 2009, 09:42:46 pm »
what is R5 tropism?

The links below give a good explanation. The short answer is: HIV attaches itself to either of two co-receptors, CXCR4 or CCR5 or sometimes the virus is dual-tropic and can attach to either. Most people, especially during early infection have R5-tropic virus so if there is a way to block that co-receptor, then the virus can't attach to the cell. The drugs known as Entry Inhibitors do just that. There are also promising studies using gene therapy in order to block CCR5.

There are some people who have a genetic mutation called delta 32 which results in the deletion of the CCR5 gene. If  a person is a homozygous carrier that means they get the mutation from both parents and they are essentially resistant to HIV-1 infection. Those who are heterozygous have a partial resistance.

The patient in Germany who was cured of HIV received a bone marrow transplant from a donor who was a delta-32 homozygous carrier.

LINK:

http://aids.about.com/od/aidsfactsheets/a/tropism.htm

LINK:

Understanding the HIV coreceptor switch from a dynamical perspective

http://7thspace.com/headlines/327232/understanding_the_hiv_coreceptor_switch_from_a_dynamical_perspective.html
http://en.wikipedia.org/wiki/CCR5
« Last Edit: December 25, 2009, 12:26:55 am by Inchlingblue »

Offline TheRoof

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Re: When does the latent HIV reservoir form?
« Reply #15 on: December 24, 2009, 11:31:47 pm »
Well, I found out from my doc that my labwork from last Monday had a Viral load of 60.  Not the end of the World, but not undetectable.  

Entry Inihibitors (EI's) do not work for everyone, but for about 60% of those infected by HIV they will work.  About 60% of the population is R5 tropism.  It is thought that the virus can switch, but not well understood.

When the time is right to start meds again I plan on discussing EI's with my doctor.  Our last discussion was to continue using what worked.

This is what confuses me. About the Berlin Patient. If the Chemo killed off all his cells wouldn't have the virus switched to the R4-Tropism? I also heard the R4 is more lethal for some reason. Is it true?

Since the Chemo kills off ALL your cells, does it kill of the HIV RNA too if it's in the blood?

(Two Seperate Questions kind of) Though I would assume the answer to the second question would be "NO" right? Lol

 


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