Is my virus dying ?? Lab: High CD4 / CD8 / Lymphocytes counts

[John2038]

Hi,

my last lab provided the following results:

Total Lymphocytes:60.2% 5.15 x 10^9/L  (1.0-4.0)
CD4 %:16.29
CD4:812
CD8 %:68.45%  (22 - 51)
CD8:3411 (400 - 1000)
CD4:CD8:0.24  (1.0 - 2.0)

Internet reading mention:
Lymph TB, lymphoma, IRIS, etc

I will see my doc this afternoon, but I was wondering if someone have a clue, or have already faced such counts (lymphocythosis) ?

Thanks
John

Notes:
- Not on meds yet but probably very soon.
- VL unknown yet

[John2038]

Got GREAT news  !!

SYMPTOMS
1) Got swollen lymph nodes on the neck. One of them is small but hard.
2) Since few months got some night light night sweat. Light means on the neck/and or the back or the chest.
3) My body is sometime hot since few month, during the day or night, but the mouth temp have never exceeded 37C
4) Got recurrent light dizziness
5) Recently, lost 2 kg in 2 days.

That's for the bad news.

VISIT TO THE ID DOC
So went to the lab yesterday to check my counts, and got an appointment with my doc today, suspecting either:
- lymphoma
- lymph tb
- body adaptation

My ID doc prescribed me a sonar of the typhoid (neck and maxillary) to detect the eventual presence of a lymphoma.
Touching my lymphs nodes, some were apparently > 2cm.

Went to the X-Ray dept, and the conclusions is as follow:

- All lymphs node are containing fat, meaning that they all are not malignancy -> Adenopathy, no lymphoma
- There size if of 0.8 cm max. The apparent 2cm+ size is due to their proximity.
- Their apparent hardness is due to the pressure


Then went back to my ID doc, who got in the meantime my VL from the lab:
VL = 862

First comment made by the doc: you might become a LNTP. 

Apparently, the reason of my low CD4% is due to the very high CD8 count (3411 (std range: 400 - 1000)).

Will have to do a second sonar in 1 month, and follow up closely my FBC and CD8 count.

But so far, it's all good news !

John

[Dachshund]

John I'm a little confused I thought your doctor ruled out lymphoma back in November of 07?

2) I was fearing lymphoma because:
- the scan was showed few nodules (6-12mm)
- the symptoms
- the low neutrophilis level

I don't have lymphoma because:
- the bone marrow biopsy haven't shows any evidence of cancer
- The size of the nodule haven't change in size and are < 2 cm

http://forums.poz.com/index.php?topic=17274.msg219335#msg219335

[John2038]

Absolutely Dachshund !

But since then (in more of the symptoms described above), and I have discovered a hard lymph node on the neck, under the maxillary. In more, my last FBC mention "lymphocytose" next to the total lymphocytes count..

So decided to check that again !

Question on the CD4 %:

Total Lymphocytes: 60.2% 5.15 x 10^9/L  (1.0-4.0)
CD4:812 /uL
CD8:3411 (400 - 1000)

So the CD8 are +2411 out of the standard range.

As the total Lymphocytes include the CD4/8, then if I was in the standard range, the Total Lymphocytes will be of:
5.15 x 10^9/L - 2.41 x 10^9/L = 2.74  x 10^9/L

So the CD4% will become:

CD4% :  812 / 2740  [/uL] = 29.64 %

If I am correct, it means we have to check the CD8 before concluding on the CD4% !
So the CD4% alone are not a good indicator !

Am I right ??

[northernguy]

Like you I have a high total lymphocyte count, which is keeping my cd4 count high despite low %'s.  My doc has never given any particularly reason why they're high.  Ironically just today I noticed two enlarged nodes on my jaw and neck that weren't there a couple days ago.  Hopefully they're just related to my swollen eye

[bocker3]

Hey guys -- 
The most common cause of lymphocytosis is........   a viral infection!!

When you have a bacterial infection, your neutrophils are most likely to increase.
When you have a viral infection, your lymphs are most likely to increase.
and for you allergy suffers -- your eosinophils are likely to increase during pollen season (or with a parasite infection) -- eos, by the way, are the prettiest orange-red color on blood smear.   

Now, having said that, I would have also have had any hard, large nodes checked.  That would be a bigger concern than the increased number of lymphs.

Mike

[John2038]

Like you I have a high total lymphocyte count, which is keeping my cd4 count high despite low %'s.  My doc has never given any particularly reason why they're high.  Ironically just today I noticed two enlarged nodes on my jaw and neck that weren't there a couple days ago.  Hopefully they're just related to my swollen eye

About having high CD4 and low CD4%:


All 15 patients had very low levels of HIV DNA in their peripheral blood mononuclear cells (mean 32 copies/ml). A strong HIV-specific CD4 response was observed in seven patients, and a high HIV-specific CD8 cell count was seen in all 15 individuals (mean count 4,800 cells/mm3). CCR5 mutations did not appear to have a role in the spontaneous viral control these individuals achieved.

The investigators noted that patients taking potent HIV therapy who have good viral control have much lower HIV-specific CD8 cell responses than spontaneous controllers.

Three possible explanations for spontaneous control of HIV are advanced by the investigators:

    * Like long term non-progressors, an attenuated strain of HIV may be involved.
    * Particular cellular phenotypes may result in reduced susceptibility to HIV infection for CD4 cells.
    * Patients with spontaneous control may have particularly efficient immune responses.

Source : http://www.aidsmap.com/en/news/4056D943-F11C-438C-A746-06B706BB1C28.asp

Having a low CD4% can be a good news if the CD8 count is high.
Without putting both into perspective, interpretative the CD4% is meaningless and risky.

How many have misinterpret their CD4% and started HAART without knowing they might be LTNP ?
For e.g.: http://forums.poz.com/index.php?topic=20055.msg269298#msg269298

[Miss Philicia]

To summarize, I guess having a low CD4% can be a good news if the CD8 count is high.
Without putting both in perspective, interpretative the CD4% is meaningless and risky.

Does your doctor concur with this assessment?

[John2038]

He just said: "For HIV-er, be out of the range (total lymphocytes) is usual, nothing alarming"

Now, articles about a high CD8 response:

1) We wondered whether these elite controllers, while exhibiting strong HIV-specific immune responses, might have abnormally high levels of T-cell activation too, which might be a bad thing.
In fact, we found that they do. Compared to uninfected patients, they have much higher levels of activated CD8+ T cells. They even have higher CD8+ T-cell activation levels than treated patients maintaining viral suppression.

Source: http://www.thebody.com/content/toparts/art46340.html

2)  a high HIV-specific CD8 cell count was seen in all 15 individuals (mean count 4,800 cells/mm3)

Source: http://www.aidsmap.com/en/news/4056D943-F11C-438C-A746-06B706BB1C28.asp


Others articles:
http://www.aidsmap.com/cms1031885.asp
http://bloodjournal.hematologylibrary.org/cgi/content/full/104/4/942

In conclusion, it make sense to says that:
A relatively (to the std range) low CD4%,  if correlated with an increase of the total lymphocytes count (CD8 increase) can be a good news.

Example:

Total Lymphocytes: 60.2% 5.15 x 10^9/L  (1.0-4.0)
CD4: 812 [/uL]
CD8: 3411 [/uL] (400 - 1000)

Extra CD8 population: +2411 [/ul]

As the Total Lymphocytes include the CD4/8, the readjusted CD4% become (removing the extra CD8 population):
5.15 x 10^9/L - 2.41 x 10^9/L = 2.74  x 10^9/L

So the CD4% become:

CD4% :  100 x 812 [/uL] / 2740 [/uL]  = 29.64 %  (instead of 16.3 %)

If we think about it, the CD4% is meaningless !
What count the most is the absolute CD4 count as it is per [uL].
Its percentage is just relative. To what, nobody talk about that. And that's the problem.

Illustration
Having CD4 = 812  CD8 =3411 and VL = 862 means almost:

1 CD4 + 4 CD8 per virus.  More talkative than a CD4% as someone with 40% CD4 can have for e.g 1 CD4 + 0.5 CD8 per virus.

In some cases (stabilization) I guess the CD4% might shows over time a trend in the immune system health.

EDIT: Highlighting numbers to make them more readable

[redhotmuslbear]

If we think about it, the CD4% is meaningless !
But what count the most is the absolute CD4 count as it is per [uL].
Its percentage is just relative. To what, nobody talk about that. And that's the problem.

John,
"The problem" is that you are playing games with numbers to achieve a number you are willing to accept, instead of dealing with the numbers as they are..... perhaps you should be in the Bush White House?

CD4 and CD8 absolute numbers are NOT measured directly.  The scientfic assays determine an absolute number for the lymphocytes, along with percentages for CD4s and CD8s.  To produce the "absolute" CD4 and CD8 counts, their percentages are multiplied by the total absolute number.  So, yes, your CD4 absolute number looks healthywhile the percentage looks bad, due to the increase in killer and suppressor cells to battle an infection. 

Knock down the infection, and the non-CD4s should go down, thereby increasing your CD4 percentage--and that may mean taking HAART meds.  Ignore the infection, and your CD4s may be depleted by HIV.

If your doctor is holding out hope for your being an LTNP, is he willing and able to get HLA haplotyping done, as well as delta-32 testing?

Cheers,
David

[John2038]

"The problem" is that you are playing games with numbers to achieve a number you are willing to accept, instead of dealing with the numbers as they are..... perhaps you should be in the Bush White House?

Really no.( My first post doubting about the meaning of the CD4% has months, so far before I get my lab this week, and the first time with the CD8 count).

CD4 and CD8 absolute numbers are NOT measured directly. 

So what ? This have no impact on what have been said above.

Knock down the infection, and the non-CD4s should go down, thereby increasing your CD4 percentage--and that may mean taking HAART meds.  Ignore the infection, and your CD4s may be depleted by HIV.

True with drugs and CD8, so..

With all my respects redhotmuslbear, nothing have been demonstrated (fortunately !)

[frenchpat]

As the total Lymphocytes include the CD4/8, the reajusted CD4% become (removing the extra CD8 population):
5.15 x 10^9/L - 2.41 x 10^9/L = 2.74  x 10^9/L

John,

I am wondering if you are not confusing CD types with T and B types, as, if my memory serves right, there are other subtypes such as CD16, CD56, CD3,
 CD19, and CD21. I may be wrong but think that CD4/8 do not constitute 100% of your lymphocites.

just asking...


Pat

[John2038]

I am wondering if you are not confusing CD types with T and B types, as, if my memory serves right, there are other subtypes such as CD16, CD56, CD3,
 CD19, and CD21. I may be wrong but think that CD4/8 do not constitute 100% of your lymphocites.

.. and the calculation above of the CD4% is indeed make against all this population (Total Lymphocytes Count), and not only the CD8.

So the calculation is correct.

[redhotmuslbear]

.. and the calculation above of the CD4% is indeed make against all this population (Total Lymphocytes Count), and not only the CD8.  So the calculation is correct.

No, your calculation is not correct. 

As has been stated before, the lab gave you a CD4 percentage observed when they observed the total cell count -- it is what it is, and you don't get to adjust it by lowering the lab-calculated (not aobserved) CD8 absolute number.  Stop obsessing over the CD4 percentage and attempting to generate one that you like -- when the number of CD8s come down, the observed CD4 percentage should rise if their numbers have not been depleted by the virus or de-activation.

A year into dealing with HIV, your mental energy can be better spent on things other than mathematical contortions and attempting to disprove long-established science.

[bocker3]

Example:

Total Lymphocytes: 60.2% 5.15 x 10^9/L  (1.0-4.0)
CD4: 812 [/uL]
CD8: 3411 [/uL] (400 - 1000)

Extra CD8 population: +2411 [/ul]

As the Total Lymphocytes include the CD4/8, the readjusted CD4% become (removing the extra CD8 population):
5.15 x 10^9/L - 2.41 x 10^9/L = 2.74  x 10^9/L

So the CD4% become:

CD4% :  100 x 812 [/uL] / 2740 [/uL]  = 29.64 %  (instead of 16.3 %)

If we think about it, the CD4% is meaningless !
What count the most is the absolute CD4 count as it is per [uL].
Its percentage is just relative. To what, nobody talk about that. And that's the problem.

Illustration
Having CD4 = 812  CD8 =3411 and VL = 862 means almost:

1 CD4 + 4 CD8 per virus.  More talkative than a CD4% as someone with 40% CD4 can have for e.g 1 CD4 + 0.5 CD8 per virus.

In some cases (stabilization) I guess the CD4% might shows over time a trend in the immune system health.

EDIT: Highlighting numbers to make them more readable

John,

I understand what you are trying to demonstrate in this example, but you really can't do that.  The assumption that you are making is that the only thing being impacted are CD8+ cells, but you do not know that.  Whatever is causing the CD8+ increase, could be impacting other lymph subsets, so your calculation is really suspect.  For example, maybe whatever is going on is raising ALL your lymph subsets and all you've done is remove the "excess" cd8+ ones.  Alternatively, maybe the increase in CD8+ cells is causing your body to produce fewer CD4+ cells and you aren't "controlling" for that in your re-calculation.  Bottomline, you are assuming too much. 
The fact is -- your T-Cell panel is what it is.  They way I interpret your results (the 4 in your signature line, that is) would be that your CD4 is pretty stable.  your percentage has not changed in any significant way.  The absolute number can swing around a bit (although, yours really isn't swinging much), the CD4% should be used to see if a change in the absolute number is "real" or do to a fluctuating total lymph count.  In fact the only result I see that is really "different" is your Feb. VL -- the other 3 are essentially the same (a VL change is only significant if it is at least 3x different)

It is dangerous to focus on any single result in lab work -- it is important to look at things holistically and historically.  I say this with experience -- I spent over 12 yrs working in clinical labs -- 6 of which where in Hematology and Special Hematology (although, I never, personally, performed CD4/8 panel testing)
While US Guidelines for when to start therapy used to have both an absolute CD4 range and a CD4%, I only see absolute number recommendations now (although I did a fairly quick skim of the doc).  So, based on absolute numbers you are perfectly fine.  You would not seem to be at risk for OI's.

It is good to look at and understand your lab results -- you just have to avoid obsessing about any one number and you certainly can not simply start recalculating things to fit your desired outcome.  The procedures have been put together after extensive testing and are what they are.

Mike

[John2038]

bocker3

thanks for your feedback. But I will repeat:

Based on many concordantly studies (see above) suggesting an important relationship between the CD8 response quality and immune control, it appears that (I repeat my conclusion above):

A relatively (to the std range) low CD4%, if correlated with an increase of the total lymphocytes count (CD8 increase) can be a good news.

2 reasons at least for that:

1) If for a poz, be an Elite controller/LTNP/Slow Progressor is a good news, and if these people have a high CD8 response (generally observed) then :
i-   as we know that these people progress slowly, it means that we can't compare at least their CD4% as we could with those very unfortunately who  do not shows such CD8 response

ii-   what should then be considered is the absolute CD4 because there is good reason to think that the CD4% is then meaningless (as a probable consequence of the CD8 increase -visible in the CD8 count at least).

2) no matter how are bouncing the others CDs count, at least the contribution of the CD8 increase is visible.
So the calculation above is an example of what could be the CD4% assuming that just only the CD8 were impacted.

It doesn't matter if others CDs change, its just an illustration.

As such, I maintain my conclusion.

Thanks,
John

Note:
- Among many others studies, see also http://bloodjournal.hematologylibrary.org/cgi/content/full/107/12/4781
- Sure, it is likely I would like to conclude so, as it might says that I could be a LTNP. But it's too early to says so.
My point is mainly to say "do not look closely to your CD4%, a low value might be a good news. So do not stress nor jump on meds"

[RapidRod]

A low CD4% is never a good sign.

[John2038]

A low CD4% is never a good sign.

And a relatively low CD4% ?

Thanks to provide your arguments as you will probably answer "same" 

[bocker3]

John,

Why do you even bother to post on this site.  You simply disregard whatever evidence anyone shows you.  You have your conclusion and rather than read and digest what others have said to you, you read other's post with an eye on how you will pull it apart -- how it doesn't fit your view (and it is YOUR view -- you are cherry picking articles and grabbing onto the pieces that YOU like).

Case in point -- I never made a comment about your conclusion (although I did comment on how I understood what you were trying to do) -- rather I attempted to show why your re-calculation of your lymph subset was wrong, illogical and a waste of time -- because you are making far too many assumptions.  Your response back to me was that this was an illustration to support YOUR CONCLUSION.  This is hogwash -- your results, barring a lab error, are what they are and no amount of mental calisthenics are going to change that.  You need to take a deep breath and start accepting your new reality -- you are HIV positive and have to deal with it as it exists.

Are you a LTNP?  Who knows -- I hope you are, truly I do.  Do CD8s play a role in LTNPs??  I don't know, but you speak like it is a fact and I daresay, if it were a fact, we would be seeing attempts made to increase CD8 levels as a way to treat HIV infection -- I've yet to see much literature about that.

So -- seeing as you are a scientist -- start acting like one.  Read other posts with a truly open mind -- digest it a bit and if you still disagree, try not repeating what you already said, but rather try to explain why what was said is not correct.  I would certainly not try to debate physics with you, as that is not where my education lies, but it does lie in the area of Laboratory Medicine, so please keep that in mind.

Mike

[Dachshund]

Guys I'm afraid you're...



[attachment deleted by admin]

[John2038]

bocker3

we definitely need to have a beer no ?

Otherwise you said evidence or others post on this subject ?
Ok, I'd like to read them, and then, I might agree definitely with you.

[bocker3]

Well, thanks for the invite -- but I had my last drink in Oct. 1989, so I'll have to stick to a glass of seltzer.   

your response here is exactly what I was getting at -- you are totally dismissing what I've said earlier without really understanding my point, so I will try, one last time, to restate it:

The "evidence" I spoke of, was not from an article, but from my experience (4 yrs of college and 12+ yrs work experience) -- you can't re-calculate a lab result the way you did and have it mean anything.  The result is the result.  Every lab procedure is based on science, you can't adjust one factor and assume that all else remains the same, that is simply not how biology works.  Regardless if the CD8 is somehow affecting how the result should be interpreted, you can't just change one parameter and recalculate.  Now, your overall assumption of a low CD4% being "less bad" with a high CD8 count, may or may not be true -- I was not (and am not) commenting on that.  I was simply commenting on your indiscriminately changing a calculation used in arriving at a laboratory result.

Mike

[redhotmuslbear]

Thanks, Mike, for giving John the written drumming he's needed desperately, even if he *still* doesn't get it and likely never will.... there's always the Ignore button, though one hates to use it....

As for CD8s and LTNPs, there are some of us who have "CD8-mediated immunity," thanks to certain genes.  Off meds my CD4 count looks normal, but the CD4/CD8 looks terribly low (0.80-0.85), though the ration was normal while I was on meds.  However, my study docs believe that my brand of CD8-mediated immunity is only a part of the LTNP puzzle, and in my case the one copy of delta-32 is the remainder.

Namaste,
David

P.S.  I took care of the beer this afternoon.  Soaked some spicy cheddar bratwursts in a bottle of a local microbrew and finished a couple bottles with my neighbor while grilling the brats.  Did you smell them down there in Richmond?

[bocker3]

P.S.  I took care of the beer this afternoon.  Soaked some spicy cheddar bratwursts in a bottle of a local microbrew and finished a couple bottles with my neighbor while grilling the brats.  Did you smell them down there in Richmond?

You know, Sid and I were wondering what that smell was while we were sitting by the pool today.
I do love a fat tasty brat   

Mike

[John2038]

So I suggest the beer and you go without me ?

Nevermind. Regarding the CD4%, you want to compare those with high immune reaction (involving the CD8 for e.g.), and those without such reaction. while it is very possible that this CD8 increase might impact significantly the CD4%.
Neither you or me have evidences, so you conclude you are right.
Time will say.

[bocker3]

So I suggest the beer and you go without me ?

Nevermind. Regarding the CD4%, you want to compare those with high immune reaction (involving the CD8 for e.g.), and those without such reaction. while it is very possible that this CD8 increase might impact significantly the CD4%.
Neither you or me have evidences, so you conclude you are right.
Time will say.

I know I'm beating a dead horse, but.............

Stop being so defensive and reread what I've stated above and what I'm about to state again.

I am making NO COMMENT about your overall conclusion -- I am simply telling you that you can NOT recalculate a lab result to make it fit what you think it should be.  Doing so constitutes bogus science.  You are free to interpret the result however you'd like (although, without an MD degree and given your overwhelming desire to have outcomes that fit your way of thinking, vs. what constitutes reality, I would be very careful here too) but you can NOT change the result based on your whim.
I do not "conclude" this -- this is a fact - born from my education and my experience (not too mention a wee bit of common sense)!  Just like 2 + 2 = 4 now and forever, your CD4% is what is, based on your blood sample at that time,  now and forever.  I do not need "evidence" to know 2 + 2 = 4 and do not need evidence to know your results are your results (unless you can show that the lab made an error, your result is all the evidence that is needed).

So again -- stop formulating your response and go back over what I've written.  You can say anything you like, but your result will always be what it was found to be.  Interpret it however your fancy dictates, I don't care, but don't try and to create a new result to fit that.

Mike

[John2038]

I am making NO COMMENT about your overall conclusion

So it's either that:



or that:



as if you do not disagree with the overall conclusion, you disagree with the example.

[Dachshund]

You know John you really are quite rude. People have been kind enough to offer you well intentioned and reasoned answers to your nonstop selfindulgent queries and as in every other thread you post you end up mocking them. You don't want answers or healthy debate you want ammo.

You'd do well to read the fable The Little Boy Who Cried Wolf.

[John2038]

HIV teach me to not surrender.

Now I really appreciate bocker3, at least he have his view (maybe right) and I have mine (maybe wrong).

But to change a mind, you need to convince.

[aliveinla]

My view: number is just number. what's more important is how we feel.

John, your CD4 number looks great and we talked about that when I first diagnosed, but I also happen to notice your "symptoms" and low CD4%. I am still new to this, but aren't being LTNP needs to be symptom free, as the #1 pre-requisite?

[bocker3]

So it's either that:



or that:



as if you do not disagree with the overall conclusion, you disagree with the example.

John,

I disagree with your attempt to view the world through rose colored glasses.

I am not really going on and on for your sake here -- it is for the sake of others who may be led astray by your mental contortion.  You are free to interpret your lab results in any freaking way you want to interpret them.

I am making no comment on your conclusion, because I have no basis to go one way or the other -- unlike you, when I don't know enough about something I either ask questions or refrain from making things up.  The only point I have been trying to make (one that, seemingly, everyone but you is able to grasp) is that you can't change your lab result to suit your desired outcome.  I have tried to be civil and logical, but clearly I am dealing with someone of the same intellect as George Bush.  So go on and continue to state your own delusional facts and ignore any real facts given to you.  
Come back and talk intelligently about this after you've spent 4 years studying Medical Technology and/or have gained valuable, real world, experience working in clinical laboratories -- Until then, you really should open your mind and shut your mouth to learn things that just might benefit your ass down the road.

If my experience can't convince you of the insanity of "reworking" your lab results, than you go on living in your own world -- it seems to work for Bush.

Mike
(who is officially done with you)

[thunter34]

You know John you really are quite rude. People have been kind enough to offer you well intentioned and reasoned answers to your nonstop selfindulgent queries and as in every other thread you post you end up mocking them. You don't want answers or healthy debate you want ammo.

Happens with every thread you start, John2038.  It's not as if it is going by unnoticed.  Keep it up, by all means.  It's only a matter of time until you are either weeded out of here or people just ignore you altogether.

[Miss Philicia]

or people just ignore you altogether.

Oh, I think that happened for most of the board with John's "Does HIV make you horny?" thread, which of course he ran away from.

[John2038]

aren't being LTNP needs to be symptom free, as the #1 pre-requisite?

True I guess.

Now no more symptoms.
The hard lymph node is a fatty lymph node.
It looks hard as to feel it, I have to keep swallowing, putting it under pressure and appearing consequently hard.

Since few days, lymphs nodes have decreased in size by 50%.

Each time I have feel symptoms and made a blow draw, the count have improve.
The symptoms listed above are very light.

FYI, this is how look a fatty lymph node:



When a lymph node is malignant, it burn the fat.
The fat in a lymph node is not correlated to the body fat.