Undetectable = 137,500 on average

[hotpuppy]

I was crunching numbers and thought this was food for thought......

Undetectable is less than 50 copies of virus per millileter of blood.  A millileter (ML) is about a drop btw.

The average person has 5.5 liters of blood, which means you have 5500 ml of blood.

So if we err on the conservative side and say that undetectable means 40 copies / ml that means the average person has a viral load of 137,500 copies even when undetectable.

Considering it takes only one copy to cause infection.... this provides some thought for why we see viral re-bound when we stop HAART for one reason or another.

Anyone care to comment?

[Miss Philicia]

That's why it's called undetectable rather than nonexistent.

[hotpuppy]

Agreed.... I just thought it was an interesting statistic because so many people tend to think that it is non-existant.... when it isn't. 

I have heard a couple of times that they can test lower than that, but I don't understand why it isn't routinely done.

[GSOgymrat]

And that is just blood. It is also in other parts of the body.

[Ann]

I have heard a couple of times that they can test lower than that, but I don't understand why it isn't routinely done.

That's because they're newer tests and therefore more expensive. When the cost comes down, they will be routine. After all, it's only a few years ago that undetectable meant under 500. As the tests improved and the price came down, so did the bar for undetectable.

[hotpuppy]

Ah.... okay....  thanks Ann. 

and GSO brings up a good point.... I'm just talking blood... not Semen or other fluids.  However, um, on second thought I won't try to quantify that.... we'll just settle on... um... yea more then just blood.   

[bocker3]

That's because they're newer tests and therefore more expensive. When the cost comes down, they will be routine. After all, it's only a few years ago that undetectable meant under 500. As the tests improved and the price came down, so did the bar for undetectable.

There was a time that I received all the viral load tests for multiple labs in Boston -- back then undetectable was <10,000 copies.  Makes <48 that I get on myself today not seem so high.....

Mike

[hotpuppy]

I think it is absolutely progress, and I hope my comment doesn't seem like an attack on where we are.  I just have seen some posts where people draw the conclusion that undetectable=zero and that simply isn't the case....

The Swiss study has been interpreted by some as a license for unprotected sex.  I was responding to something else when i pondered these numbers and I thought it was an interesting point of consideration....

[tednlou2]

I thought I read somewhere when someone is UD, their true viral load could still be like 1 million in those hidden reservoirs.  I've tried to find that article, but can't.  Does that sound right?

Edited for spelling

[Hellraiser]

I think it is absolutely progress, and I hope my comment doesn't seem like an attack on where we are.  I just have seen some posts where people draw the conclusion that undetectable=zero and that simply isn't the case....

The Swiss study has been interpreted by some as a license for unprotected sex.  I was responding to something else when i pondered these numbers and I thought it was an interesting point of consideration....

The Swiss study is an attempt to link the level of virions in the blood to the level of virions in sexual secretions.  The two don't always correlate with one another, but on the practical side of the study you had people with an undetectable viral load having unprotected sex with negative partners for years and not transmitting the virus.  This is good news for those of us who want to get on the "treatment as prevention" bandwagon.  Convincing an hiv- sexual partner to have sex with someone who is hiv+ sans condoms based on a single study...dunno about all of that.

[mecch]

undetectable does not equal 0 - duh dont we all know that - or at least have been told so?

On the other hand, I think your formula about how many viruses an undetectable has is pretty flimsy and probably not even related to the real situation.

Also, my understanding was that as far as blood goes, effective HAART could result in no viable virus circulating and the tests are measuring "dead" virus.

[edfu]

This obsession with measurement of virus in peripheral circulating blood can truly be brought to a dangerous, misleading, and meaningless extreme.  Current measurement of viral load, outside of very specialized research facilities, does not measure viral load in the gut, in the testes, in semen, in lymph nodes, in the brain, and in other, still unknown, reservoirs.    

[veritas]

Nice post edfu. Since the amt of virus in one's blood is roughly 2% of the total amt in one's body, this thread is somewhat" tardus".

v

[hotpuppy]

The Swiss study is an attempt to link the level of virions in the blood to the level of virions in sexual secretions.  The two don't always correlate with one another, but on the practical side of the study you had people with an undetectable viral load having unprotected sex with negative partners for years and not transmitting the virus.  This is good news for those of us who want to get on the "treatment as prevention" bandwagon.  Convincing an hiv- sexual partner to have sex with someone who is hiv+ sans condoms based on a single study...dunno about all of that.

While I agree that there is a correlation between viral load and "infectability"...... it isn't a greenlight for serodiscordant unprotected sex.  Yet people do seem to do exactly that.

The more important issues is that reducing viral load improves health and do we need any other reason to get people on treatment?  Isn't it just a tad selfish to put people on treatment motivated by prevention?  That's discounting the needs of the infected and placing a premium on the perceived needs of the uninfected.  In essence it's what I label containmentism.  Because in containmentism, the "bug" is our problem and "we" need to "keep" it to ourselves.  um, okay..... BS.  My point in this section is that reducing viral load for the sake of reducing viral load is ALL we need.  Treatment as prevention is a red-herring that doesn't work for our ultimate benefit even if it sounds nice.  Isolation as prevention accomplishes the same outcome for a heck of alot less cost to society and I'm sure none of us are on that bandwagon.  I might add that Cuba used Isolation as Prevention quite effectively for many years.

Heck, I've even noticed people expressing a preference for "undetectable" sex partners as opposed to "positive" partners on a website that I belong to.  So you see even an inkling of what I can only classify as stigma based on viral load....

All of which reinforces why I made this post, just to make readers think for a second.

[newt]

I thought I read somewhere when someone is UD, their true viral load could still be like 1 million in those hidden reservoirs.  I've tried to find that article, but can't.  Does that sound right?

No. Viral load in blood is a reilable measure of viremia, and on treatment usually matches well with viral load in other parts of the body. If viral load is higher here it tends to be no more than 1 log higher (ie add '0' to the end of your blood measurement). This is pretty much established as the picture for semen, CSF etc.

- matt

[hotpuppy]

Nice post edfu. Since the amt of virus in one's blood is roughly 2% of the total amt in one's body, this thread is somewhat" tardus".

v

Perhaps you would care to back that up?

I'm not so sure you are right and here's why I think your post is wrong.

What we know about HIV:
- needs CCR4 or CCXR5 receptor to gain access to cell.
- only infects cells with these receptors expressed.

What we know about these receptors:
- Primarily found on immune related cells, in particular macrophages, CD4 (t-cells), and a few others.

What we know about these cells (T-cells in particular):
- They live in the blood
- They are born in the thymus, a small gland in the chest.
- They are produced constantly and take some time to mature.
- The rate of production decreases gradually as we get older.

So to make the assertion that HIV is in other tissues has merit.

To make the assertion that it is minute in the blood and greatly elevated in other tissues just doesn't pass muster.

Here is a study from 2009 and an excerpt from it on the subject of HIV in semen.


In 85% of sample pairs, HIV RNA was undetectable in both plasma (< 40 copies/mL) and semen (< 200 copies/mL), while in 3.4% of pairs it was detectable in both. In 8.7% of sample pairs, however, HIV RNA was undetectable in semen despite being detectable in plasma, while in 2.7% of pairs (coming from 4.8% of the men), HIV was detectable in semen but not plasma; in all the latter cases, the men were on stable ART and had fully suppressed plasma HIV RNA for at least 6 months. Here too, detectable semen viral load often occurred as transient "blips."

Basically what they are saying is that they occassionally could find HIV in Semen.  Note, that the detectable threshhold is 5x higher for Semen.  I'd like to point out what they aren't saying as well as what was said elsewhere in the article.

1- It isn't massively higher.  
2- Blips in testing indicate fluctuations.. meaning that just because it is high in 1 test doesn't mean it will be consistently high.
3- Blips are consistent with the reality that your body is not a set of legos, but a dynamic system of cellular entities that is always in a state of change.

Back to what they are saying:
- A small proportion of people who are "undetectable" have HIV in their semen from time to time in minute quantities.
- It didn't seem to matter if you had been undetectable for 4 years,or 6 months.

Here's the link:http://www.hivandhepatitis.com/2009icr/croi/docs/022409_c.html
The source for the information is a respectable entity: 16th Conference on Retroviruses and
Opportunistic Infections (CROI 2009)

There was a very interesting study footnoted in this article about "free HIV" in semen and linking it to actual infection.  Unfortunately, that study wasn't tied to the undetectable factor.  It certainly looked like a smoking gun.......

[RapidRod]

No. Viral load in blood is a reilable measure of viremia, and on treatment usually matches well with viral load in other parts of the body. If viral load is higher here it tends to be no more than 1 log higher (ie add '0' to the end of your blood measurement). This is pretty much established as the picture for semen, CSF etc.

- matt

I have a blood serum VL of undetectable I have a semen VL of 4800 so no it does not match the established picture. They don't even correlate.

http://www.aidsmap.com/en/news/C6491E0E-B323-480A-975B-7DFC4966539F.asp

http://www.hivandhepatitis.com/recent/2008/090508_f.html

[veritas]

hotpuppy,

That figure has been known since 2001:

"From the onset of infection, HIV is reproducing at an extraordinary rate. In the early to intermediate stages, the immune system can mount a defense that keeps the virus in check at its set point. The virus's replication rate is higher in the lymph nodes than in the plasma. In fact, only 2% of the virus are in the circulating blood and the rest is in lymphoid organs. After years of battling, the immune system starts to deteriorate and the body moves into the downward spiral of the disease."

Here's a refresher on hiv 101:

http://uhavax.hartford.edu/bugl/hiv.htm

v

[mecch]

While I agree that there is a correlation between viral load and "infectability"...... it isn't a greenlight for serodiscordant unprotected sex.  Yet people do seem to do exactly that.

The more important issues is that reducing viral load improves health and do we need any other reason to get people on treatment?  Isn't it just a tad selfish to put people on treatment motivated by prevention?  That's discounting the needs of the infected and placing a premium on the perceived needs of the uninfected.  

First you created a false measurement to support this coming argument. And now we see the argument. But who is putting a gun to HIV+ peoples' heads saying go on treatment to prevent transmission? If the HIV+ wants to do it for that, its not unfounded - undetectable viral loads DOES reduce transmission.

In essence it's what I label containmentism.  Because in containmentism, the "bug" is our problem and "we" need to "keep" it to ourselves.  um, okay..... BS.  My point in this section is that reducing viral load for the sake of reducing viral load is ALL we need.  Treatment as prevention is a red-herring that doesn't work for our ultimate benefit even if it sounds nice.  Isolation as prevention accomplishes the same outcome for a heck of alot less cost to society and I'm sure none of us are on that bandwagon.  I might add that Cuba used Isolation as Prevention quite effectively for many years.

WTF?  Treatment as prevention CERTAINLY works for HIV- people, and that is a valid argument for HIV+ people to consider.

Heck, I've even noticed people expressing a preference for "undetectable" sex partners as opposed to "positive" partners on a website that I belong to.  So you see even an inkling of what I can only classify as stigma based on viral load....

All of which reinforces why I made this post, just to make readers think for a second.

You made me think for a second to see you have half baked ideas. Not entirely wrong but used in a false dichotomy.  There is no US and no THEM.  We are all in this life together, baby.

[Inchlingblue]

I thought I read somewhere when someone is UD, their true viral load could still be like 1 million in those hidden reservoirs.  I've tried to find that article, but can't.  Does that sound right?

Edited for spelling

According to Siciliano:

. . . the size of a latent reservoir in resting T cells is very small. It's one in a million cells.*

That still means we're talking millions of cells that make up resting T cell reservoirs, so yes the reservoirs have millions of copies of virus but they are not actively replicating.

LINKS:

http://www.thebody.com/content/toparts/art50467.html

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


*I don't remember off the top of my head how many millions of total cells there are but it's enough that if you say "one in a million" it still adds up to 1 million or more reservoir cells that harbor HIV. It's still a tiny amount relatively speaking.
 

[Ravhyn]

I didn't know that under 50 copies meant you were UD...man I need to do more studying LOL.  that means I've been UD from the start woot!

[Hellraiser]

I didn't know that under 50 copies meant you were UD...man I need to do more studying LOL.  that means I've been UD from the start woot!

Actually it varies depending on what test is being used.  If they give you a quantified number then you are not "Undetectable" if they can't detect any copies of the virus then they will tell you it's Undetectable.

[Ravhyn]

aww I got all excited my paperwork said <48 copies. 

[Boze]

hotpuppy,

That figure has been known since 2001:

"From the onset of infection, HIV is reproducing at an extraordinary rate. In the early to intermediate stages, the immune system can mount a defense that keeps the virus in check at its set point. The virus's replication rate is higher in the lymph nodes than in the plasma. In fact, only 2% of the virus are in the circulating blood and the rest is in lymphoid organs. After years of battling, the immune system starts to deteriorate and the body moves into the downward spiral of the disease."

Here's a refresher on hiv 101:

http://uhavax.hartford.edu/bugl/hiv.htm

v

You made it sound like HAART just gets rid of the virus in blood, while the other 98% continue to live unperturbed. I understand that HAART removes most virus from the body, except the latent reservoirs.

With regard to HVI showing up in semen for UD blood test - it does happen, but INFREQUENTLY. I saw a study somewhere that cited 3%, another 14.

Either way - on the topic of treatment as prevention - I think it's the best strategy we have now. We've all seen the studies - people with UD VL simply don't transmit (most recent study had 1 transmission out of 103 serodiscordant couples on HAART  and that 1 just started on HAART so was probably not UD).

[bocker3]

aww I got all excited my paperwork said <48 copies.  

If your result was <48, then you ARE undetectable.  

[Inchlingblue]

aww I got all excited my paperwork said <48 copies.  

If your results said "<48" that does mean undetectable because the test used cannot detect copies below 48.

There are more sensitive tests beginning to become available. I think this is what Trey was referring to. These newer assays are able to detect below 48 and give a result with a specific number, say, 12. So technically it's not "undetectable" because you are getting an actual amount that was found or "detected."

But for all intents and purposes (or as a friend of mine used to say "for all intensive purposes," lol) if your results are <48 then, as bocker3 says, you are considered to be undetectable.

This small amount of virus in the blood when a person is undetectable (called residual viremia) is coming from the reservoirs as they slowly get depleted. There have been some mathematical models that have predicted it would take about 60 years for the reservoirs to empty out, as it were, if a person were on HAART and undetectable the whole time.

So, based on current treatment standards, someone who is 20 years old who gets HIV and starts meds and stays undetectable would be HIV-free by the time they are 80! Or at least that's what some scientists predict.

[Inchlingblue]

You made it sound like HAART just gets rid of the virus in blood, while the other 98% continue to live unperturbed.  

That is indeed what happens. HAART is only able to get at the virus in the plasma (blood). The rest of the virus , which is in the reservoirs (whatever percentage that may be), does remain "unperturbed," because HAART cannot reach it.

HAART can only reach viral particles that are actively replicating, the virus in the reservoirs is lying dormant (there is actually some duplication or "homeostatic proliferation," but it's not actively replicating).

If HAART could get at the virus in the reservoirs we'd all be cured.

[Boze]

That is indeed what happens. HAART is only able to get at the virus in the plasma (blood). The rest of the virus, which is in the reservoirs, does remain "unperturbed," because HAART cannot reach it.

HAART can only reach viral particles that are actively replicating, the virus in the reservoirs is lying dormant (there is actually some duplication or "homeostatic proliferation," but it's not actively replicating).

If HAART could get at the virus in the reservoirs we'd all be cured.

But that means that reservoirs contain 98% of the virus? That doesn't make sense.

[Inchlingblue]

But that means that reservoirs contain 98% of the virus? That doesn't make sense.

Once a person is undetectable in the blood, the only virus that remains is in the reservoirs and HAART cannot reach that.

I'm not sure what you mean by "that means that reservoirs contain 98% of the virus"? 98% of what?

[Boze]

Once a person is undetectable in the blood, the only virus that remains is in the reservoirs and HAART cannot reach that.

I'm not sure what you mean by "that means that reservoirs contain 98% of the virus"? 98% of what?

Veritas said that blood only has 2% of the virus in the body, I was referring to that.

[Inchlingblue]

Veritas said that blood only has 2% of the virus in the body, I was referring to that.

I'm not sure where the source he cites came up with 2% since plasma viral load can vary widely depending on whether a person is undetectable and has a minimal amount of virus coming from the reservoirs or if someone is not on meds and has a viral load in the millions.

Once HAART is initiated, viral replication is essentially halted. Both Siciliano and Chomont have found that there is no active viral replication in the reservoirs. Chomont found what's called "homeostatic proliferation," which is more like cell duplication but it's not active replication.

HAART meds affect different points in the HIV life cycle (i.e. when it produces integrase or protease or reverse transciptase, etc); precisely because the virus in the reservoirs is not actively replicating is why HAART cannot reach it. There are various studies looking at "waking up" virus in the reservoirs so that it can begin to replicate and become susceptible to HAART.

 

 

[GSOgymrat]

Once HAART is initiated, viral replication is essentially halted. Both Siciliano and Chomont have found that there is no active viral replication in the reservoirs. Chomont found what's called "homeostatic proliferation," which is more like cell duplication but it's not active replication.

HAART meds affect different points in the HIV life cycle (i.e. when it produces integrase or protease or reverse transciptase, etc); precisely because the virus in the reservoirs is not actively replicating is why HAART cannot reach it. There are various studies looking at "waking up" virus in the reservoirs so that it can begin to replicate and become susceptible to HAART.

That is assuming that HAART remains effective, correct?

[Boze]

I'm not sure where the source he cites came up with 2% since plasma viral load can vary widely depending on whether a person is undetectable and has a minimal amount of virus coming from the reservoirs or if someone is not on meds and has a viral load in the millions.

Once HAART is initiated, viral replication is essentially halted. Both Siciliano and Chomont have found that there is no active viral replication in the reservoirs. Chomont found what's called "homeostatic proliferation," which is more like cell duplication but it's not active replication.

HAART meds affect different points in the HIV life cycle (i.e. when it produces integrase or protease or reverse transciptase, etc); precisely because the virus in the reservoirs is not actively replicating is why HAART cannot reach it. There are various studies looking at "waking up" virus in the reservoirs so that it can begin to replicate and become susceptible to HAART.

 

Thanks. But then - since we were talking about infectiousness - the virus that's latent in the reservoirs can not be passed on? That would require fresh viruses to be made in sperm/vaginal fluids?

[eric48]

Hi,

I just made the calculation on an other post that going from 68 K to 600 and assuming 5 liters of blood
has deleted 340 millions virions

(about the population of the US...)

One thing of interest to me... Do people who are small and slim (like myself) and are UD have less virus than somebody, say, twice as big (massive) ans also UD ?

I have always wondered because:
- why meds dosage for me are the same as for a super big guy ?
- does average time-to-mutation in UD people relates to their blood/body mass ?
(I would assume that time-to-mutation, would, on average, relate to the TOTAL number of virri (blood+reservoirs) in the body.

Well, that is a question I am asking myself

Cheers everyone

Eric

[nixsmail]

eric, i'm not sure cause i'm not a doc, but i think we all have about the same amount of blood whether we're slim or bulkier. so getting rid of the active virus should or would take the same amount of medication. but the absorption by each individual, whether large or small, is just that individual. i think that the medication is made to cover everyone rather than having to make a million different size differences. and yes i know that "a million" is an exaggeration.

[newt]

I have a blood serum VL of undetectable I have a semen VL of 4800 so no it does not match the established picture. They don't even correlate.

I did not say blood and semen viral load correlate. I said, if viral load is higher in compartments compared to blood, it tends to be no more than 1 log higher, which, if you read the studies and journal correspondence you linked to, you will see is the case even here where the researchers are reporting exceptions.

The point here, going back to OP, is that I sense some people might be thinking treatment hammers the virus in the blood but leaves virus in other parts of the body unaffected. This isn't so. Treatment reduces viral load in all parts of the body eventually, even if they way it does this is sometime indirect and takes time.

- matt

[Inchlingblue]

That is assuming that HAART remains effective, correct?

Right, and there is no reason why it should not remain effective. Mutations can only happen when the virus is replicating so when HAART is able to reduce virus to undetectable levels in the plasma, there's no active replication (according to Siciliano's findings) and the meds can remain effective as long as the levels in the plasma are sufficient to suppress virus. IOW, HAART won't just stop working for no reason, it would only happen if a person is not adherent and the drug levels go low enough to allow viral breakthrough.

Thanks. But then - since we were talking about infectiousness - the virus that's latent in the reservoirs can not be passed on? That would require fresh viruses to be made in sperm/vaginal fluids?

The virus in the reservoirs is not able to be passed on while it is dormant in the reservoirs. The question then becomes: is there enough residual viremia in bodily fluids (sperm, blood, vaginal secretions) to pass it on?

The Swiss study found it to be unlikely (although not impossible).

I think the question becomes more complex when taking into account the possible presence of other STDs such as herpes (very common, even among monogamous couples both gay and straight) or gonorrhea or syphilis, etc. Any of these could be present without a person even knowing it (especially very early stages of a herpes outbreak), and this can make transmission a lot easier.

People who have genital herpes sores are more likely to be infected with HIV during intercourse. When you develop a sore, your immune system tries to heal it, so there are many immune cells concentrated in that spot. Those are the cells that HIV infects. If HIV in semen, vaginal fluid, or blood comes in contact with a herpes sore, the risk for infection is high.

LINK:

http://www.webmd.com/genital-herpes/guide/risk-hiv

[veritas]

Boze,

You asked about the 98% ---- Indirectly as Newt pointed out, if you keep your viral load ud, eventually the latent cells will be affected by not being replenished. This is what Inch was referring too, also. Meds cannot reach the virus in the resting cd4 cells. Only 2% of t-cells are present in the blood thus the ratio holds.

http://www.hiv.va.gov/vahiv?page=pr-kb-00&post=0&kb=kb-02-02-02-01&sec=11&tp=Testing&tpage=prtop02-00-rr

Nix & Eric,
The amt of blood varies by weight.  See this: http://www.buzzle.com/articles/how-much-blood-is-in-the-human-body.html

v

[mecch]

this is one messy thread

[veritas]

mecch,

I agree. Too many issues flying.

v