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Author Topic: CD4% info and Trend after treatment  (Read 7784 times)

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Offline new_2013

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CD4% info and Trend after treatment
« on: November 02, 2013, 11:23:37 am »
Hi,
   I am looking for more information regarding CD4% specifically and its link to starting meds and if there is any expected "trend" after starting treatment. Most of the info I have seen discusses CD4 count and VL.

I was diagnosed in January 2013 and my recent clinic appointment my doctor is recommending I start treatment now and I believe the main reason is my low CD4% (I live in the UK).  She is recommending Kivexa(Epzicom) AND (Efavirenz OR Rilpivitine)

10th Jan - CD4 - 507 / VL - 1669 /        CD4% - 19%
24th Jan - CD4 - 482 / VL - unknown  / CD4% - 21%
26th Apr - CD4 - 438 / VL - 98906 /      CD4% - 18%
09th Jul  - CD4 - 480 / VL - 54748 /      CD4% - 20%
14th Oct - CD4 - 432 / VL - 29197 /      CD4% - 16%

I came across this on the web (I do appreciate everyone will react differently so its just a reference to a trend)
During the first two months of therapy, an HIV-infected person's viral load should drop a minimum of 90%. In other words, someone who starts treatment with a viral load count of 100,000 should drop to 10,000 or less within two months. Within 4 to 6 months of starting therapy, the viral load should have dropped a lot more, hopefully below the level of the viral load test's sensitivity ("undetectable").

As for your CD4 cell count, you will likely see an increase between 100 and 200 cells in the first 12 to 18 months, and can gradually climb from there as long as viral load remains undetectable. Some people who start HIV treatment for the first time have a poor CD4 response despite achieving and maintaining an undetectable viral load. Researchers refer to individuals in this situation as "discordant responders." Most discordant responders waited to start treatment until their CD4 counts were well below 200. This is one of the reasons that the guidelines recommend starting ARVs earlier.

Does a similar expectation around CD4% exist?
Does anyone have a link to any information around CD4% in this range?

Thanks in advance ;-)


 

Offline eric48

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Re: CD4% info and Trend after treatment
« Reply #1 on: November 02, 2013, 12:25:17 pm »
Hi,

I started treatment as my numbers were similar to your July numbers. I take Epzicom (aka kivexa) and Viramune (as Riilripine was not available at that time)

If I had to choose between EFV and riviliripine, I'd take the later.

You can follow my experience on Epzicom here
www.tinyurl.com/HIVPharmaCure

You'll see some numbers. aand graphs towards the bottom of the thread

My doc did not push me into treatment as he was not excluding the possibility to be a controller (but this is rare). Seeing your VL going down steadily, you may want to consider postponing and see.

You are not in critical condition. Me I have never got sick

CD4 increase is a good indicator to see if people are immuno responders, but, it is biased in one way. If you consider that the average CD4 count is about 800, the potential for recovery is not the same if you start at 100 or at 700.

CD4 dynamics are poorly undertood and modelized.

Mine went up quickly to 600 - 700 where I had expected them to be.

The last summer I had a +700 jump in 2 months to reach 1400. I thought it was a lab error but later data confirmed.

A vast majority will respond both virologically and immunologically, so you should not worry. Moreover, in the (rare) case were you count gain would be modest, you are starting from a fairly safe zone, so you would at least remain where you had started from, which would provide way enough CD4 to feel safe

Epzicom is not for everyone, but those who tolerate seem to tolerate without much complaints

I do have a CD4% range table that I'll post soon (I do not have it at hand)

Your % is below range. In my case this was one factor for starting meds, but also my age (being older). The lower CD4% you have demonstrate that the CD8% is up (may be in the 50-60% , am I correct ?), they are doing their job, trying to control the infection

% recovery is not a popular concept, but you will find more lit. on the CD4/CD8 ratio
fav
70% of people under treatment will not normalize this ratio, while 30% will. Yet, depite it is conforting to normalze every thing, the is not smoking gun that says people with a non-normalized ratio are at a higher rish, or if, so this is most likely marginal (I hope...). Bear in mind that you are currently at a CD4 count way above where most people have started treatment (in the past)

Factor that favorably help normalizing the percentages are younger age, earlier treatment (before 1 year), use of NVP (sex, wine, etc. should help too!)

Hope this helps

Cheers

Eric
« Last Edit: November 02, 2013, 12:50:17 pm by eric48 »
NVP/ABC/3TC/... UD ; CD4 > 900; CD4/CD8 ~ 1.5   stock : 6 months (2013: FOTO= 5d. ON 2d. OFF ; 2014: Clin. Trial NCT02157311 = 4days ON, 3days OFF ; 2015: https://clinicaltrials.gov/ct2/show/NCT02157311 ; 2016: use of granted patent US9101633, 3 days ON, 4days OFF; 2017: added TDF, so NVP/TDF/ABC/3TC, once weekly

Offline leatherman

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Re: CD4% info and Trend after treatment
« Reply #2 on: November 02, 2013, 03:04:28 pm »
some thoughts about cd4 counts - and why NOT to worry about them

1) they can change by 100 pts a day
     so that means you can never determine anything by just one test. it's the trend over 3 or 4 tests that really gives the picture of what you count is
2) they are higher in the evening than the morning
     so getting tested around the same time of day somewhat helps with keeping more consistent labs
3) normal is 500 to 1500
    so don't get bogged down on worrying that cd4 counts aren't climbing more or faster, because that's a big damn range.
4) without having been tested BEFORE HIV, no one knows their "normal" count
5) at a certain point, it's not how many you have; but how well they work
     reading stories here, I would venture to say that my 305 (at 28 yrs poz) has kept me healthier than many in the 700-1000 range. I'm not bragging, just pointing out that more isn't always better
6) dropping to a low nadir (lowest point) can result in slow recovery and not a very large recovery

this doesn't mean that cd4 count isn't important; but the goal of ART is to reduce viral load and allow cd4s to recover. Staying UD (undetectable) is of much more importance than what your cd4 count is.

I was diagnosed in January 2013 and my recent clinic appointment my doctor is recommending I start treatment now and I believe the main reason is my low CD4% (I live in the UK).
recommendations are that meds should be started <500 cd4s. your trend clearly reflects that recommendation.  ;)
leatherman (aka Michael)

We were standing all alone
You were leaning in to speak to me
Acting like a mover shaker
Dancing to Madonna then you kissed me
And I think about it all the time
- Darren Hayes, "Chained to You"

Offline new_2013

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Re: CD4% info and Trend after treatment
« Reply #3 on: November 02, 2013, 05:42:43 pm »
Thanks Eric for your response, I had actually seen your posts earlier regarding Epzicom and found it very useful.

Thanks also leatherman for your response, also very helpful (and the quote from les mis is very touching).

I suppose where I am coming from is I don't see any reason for immediate alarm with my CD count and VL. My plan was if my CD count went below 400 or VL > 100,000 I would start meds.

My main query is my CD% which was 16% about 3 weeks ago. I am finding it hard to get any clear reference on this besides that it is low and is also a trigger to starting meds. I am also slightly concerned about references i see like "AIDS is diagnosed when an HIV-positive person's immune system deteriorates to a specific point (CD4 count of 200 or CD4% of 14%)"

With a CD of 16% should I be feeling alarmed and request meds ASAP?
Is there a "trend" for improvement in this figure after starting meds?

Offline eric48

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Re: CD4% info and Trend after treatment
« Reply #4 on: November 02, 2013, 06:25:25 pm »
Hi,

If you had been through the thread I maintain to keep V&K users posted about latest on these meds, you'll see some post coming and discussing CD4%. I am preparing them, so...they are not ready...

I found a good reference for the data you want:
http://www.uams.edu/clinlab/flow.htm

CD3:  64-82%, 1171-2005/µl
CD4:  39-57%, 720-1348/µl
CD8:  17-31%, 318-710/µl
CD19:  8-16%, 151-343/µl
CD16/56:  7-21, 145-453/µl
H/S Ratio 1.0-3.6

The H/S ratio can be calculated by dividing CD4% by CD8%.

I understand the concern with the CD4% reading at 16. It seems to have come down, but, there may be an alternative way of looking at things. For this the CD8 % data are needed.

the % vs disease progression risk shows a cliff pattern
16% is in safe zone (plateau)
15% also
14 % cliff
13 % enter serious concern

As long as you are on the plateau, it does not seem to matter if you are close to the cliff or not.

14% used to be (may be still is) a AIDS defining number as per CDC classification, but, I think there was some discussion about removing it as an event as it is more a risk. In some countries it is no more used for classification.

Yet, I wanted my bill clean of the 4 letter word, so I opted for meds.

Looking back... Well it is too late to look back.

The other day I played bad kid and I teased my doc saying:
earlier into treatment, earlier off treatment

He did not like the pun, but I am hopeful that they will find a solution, especially to allow some patients be ON-OFF. Patients allowed to do that will obviously those who have been fairing well in treatment. Initiating treatment early should favor better outcome, hence be eligible for future 'tweaks' if they ever come out.

You doc did not offer your NVP since your CD4 > 400

If you start at CD4 < 400 you can consider viramune (250 for ladies)

If you start at CD4 > 400 you can consider another NNRTI and then switch to V ( if you are uncomfortable with that NNRTI) after some month, because the ban on CD4> 400 is only for treatment naives (and after a few months, you are no more treatment naive). If you consider this strategy, then starting with EFV is better than starting with rivilripine.

This partially has to do with the size of the molecule, since NNRTIs have a steric action (they block passage by sitting in the middle of the road). Smaller molecule, better penetration, larger molecule better blockade so it comes like this:

Molecule   penetration   Virologic risk
NVP           +++            +++
EFV           ++              ++
Ril.            +                +

(all meds are approved and have well enough penetration and virologic efficacy, so the above is mostly a helper to make up you mind, no much more than that). Helps understand why some weirdos like myself still opt for NVP

Hope this helps
Eric

« Last Edit: November 02, 2013, 06:30:59 pm by eric48 »
NVP/ABC/3TC/... UD ; CD4 > 900; CD4/CD8 ~ 1.5   stock : 6 months (2013: FOTO= 5d. ON 2d. OFF ; 2014: Clin. Trial NCT02157311 = 4days ON, 3days OFF ; 2015: https://clinicaltrials.gov/ct2/show/NCT02157311 ; 2016: use of granted patent US9101633, 3 days ON, 4days OFF; 2017: added TDF, so NVP/TDF/ABC/3TC, once weekly

Offline newt

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Re: CD4% info and Trend after treatment
« Reply #5 on: November 03, 2013, 04:06:36 am »
Hello

All the big studies use CD4 count as the marker to measure. Hence precious little really good info about CD4% and starting treatment. US, European and UK guideline comment that a low CD4% may be a reason to consider treatment. A CD4% of 12-15 usually equates to a count of 200 or less. One of 29+ to a count of 500+ but there is more variation at the top end.

So, a CD4% of 16....me, personally I'd want to see what the next test says. A CD4% is the proportion of all lymphocytes that have the CD4 marker. If, say, your lymphocytes were greater because you had a cold or some other reason, the CD4% would be lower.

But also, if on the next test my CD4% was 16 or under I'd be thinking about starting meds.

- matt
"The object is to be a well patient, not a good patient"

Offline eric48

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Re: CD4% info and Trend after treatment
« Reply #6 on: November 03, 2013, 03:34:28 pm »
The question about 'trend' should be considered carefully...

Your CD4% does not exhibit a trend as per definition given here:
http://en.wikipedia.org/wiki/Trend_estimation

In particular, it may be useful to determine if measurements exhibit an increasing or decreasing trend which is statistically distinguished from random behaviour.

I guess you are considering that CD4% may have a time dependent behaviour. It does in a way, of course.

Yet, if that would be true, then the CD4% dynamics would be governed by an ordinary differential equation in the form of:
dCD4%/dt = f(t) + ...

In fact, the few models I have seen would rather be in the form of:
 dCD4%/dt = f(CD4%) + g(CD8%) + ...

Models in the form of:
dCD4/dt = f(t)+ ... do exist (unfortunatly, they do...this is called disease progression...), but usually not in the form of CD4%

On the other hand your VL is showing potential for a trend: divides by 2 every 3 months

If the next blood draw, in 3 months I suppose, gives you a VL around 15 k (or even below...), then you might have a trump card in your hand: the immune system might be able to lower VL on its own. This is rare but not unseen : you win (*)

On the other hand if VL comes back in the 50k : you don't win

(*) your doc offered Epzicom, therefore you should have the HLA***57 test done:
- if neg: Abacavir = OK  (in one way, good news)
- if + : this allel is a (modest, but widely accepted) predictor for ability to control the infection (thus, even better news) 

I'd cast vote for waiting one more draw

As per your main concern: Trend after treatment: it goes up in a vast majority of patients who start below range, so you should not be over concerned by the non-responder stuff you read here and there.

Hope this helps

Eric
NVP/ABC/3TC/... UD ; CD4 > 900; CD4/CD8 ~ 1.5   stock : 6 months (2013: FOTO= 5d. ON 2d. OFF ; 2014: Clin. Trial NCT02157311 = 4days ON, 3days OFF ; 2015: https://clinicaltrials.gov/ct2/show/NCT02157311 ; 2016: use of granted patent US9101633, 3 days ON, 4days OFF; 2017: added TDF, so NVP/TDF/ABC/3TC, once weekly

Offline new_2013

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Re: CD4% info and Trend after treatment
« Reply #7 on: November 03, 2013, 03:51:34 pm »
Thanks Eric, unfortunately I am just given the CD% in my results so cannot go into the detail you have references. You comment about strategy is useful and something I will consider.

Matt, thanks for your response also. Yes, it was the comparison of CD4% of 15% equating to a CD count of 200 that was worrying me.

I agreed with my consultant that I would start treatment next month (appointment booked for 12th Dec) but I may wait and get another set of bloods done end of Jan just for my own peace of mind (and gives me the time to research treatment options a bit more and make inner 'peace' with going on meds).

Offline new_2013

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Re: CD4% info and Trend after treatment
« Reply #8 on: November 03, 2013, 04:00:04 pm »
Eric,
   Just seen your recent post after I responded. Thanks for that, makes sense (except for the equations, maybe next year I will understand them.. ;-) )

I am veering towards "one more draw" as you say. If nothing else, it will help me 'connect' better to my body and its own behaviour during this time (if that makes sense).

Offline eric48

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Re: CD4% info and Trend after treatment
« Reply #9 on: November 04, 2013, 07:12:05 pm »
Hi,

You asked for 'trend' ;-)  that was calling for (maths) trouble. No problem, it took me months (if not years) to put that % thing into perspective.

% is very useful in clinical decision; say you are an ER doctor and have a sick patient. you have to react quick. Moreover you have to act on a snapshot of the patient's condition. This is where the % is useful.

It has long be debated which of absolute count, % or ratio (CD4/CD8) is a better 'predictor'. As far as % and ratio, in the low end, they are almost identical mathematical objects. I'll explain this in about a month or so, but, for the time being, just bear with me. 

So it is down to absolute count and whichever of the remaining 2.

Just a few inches, even an inch to that:
http://www.youtube.com/watch?v=xwoh70n0kh8

you can see fishes and dragonflies going business as usual...in a water that is virtually still

What mean here is that as long as you are on the plateau, there is no sense of danger. At 16% you are not accelerating to a fall.

Here are my numbers
18
16
20
---started meds
29
32
30
28
32
35
32
35
30

You will see mine are 16, 18, 20, like yours. Also strangely enough, I had way more even numbers than odd. I started being suspicious that the % measured in a commercial assay is not very precise or at least not as precise as you would expect. (Later, I had to rule out a bias towards even numbers, but, somehow remained uncomfortable about this)

Anyway, at 16 my % went up, so on a plateau, there is NO trend and a reading at 16 is not very different from 18 or 20.

The Lymphocyte compartment has 3 'majors' : Tcells (aka CD3+) with 2 'main' subsets CD4 and CD8 and the rest, Bcells, aka CD3-. This is a rather simplistic view but good enough to explain that , if , for some reason, your CD3- compartment has expended by 1 or 2 %, your CD4 may lose 1 or 2 %, and this has nothing to do with a 'drop', and, more importantly, nothing to do with a change in the relative density CD4 vs CD8

You are in the plateau, not in the falls. not even sufficient evidence that you are going towards the falls, so there is no real reason to rush to meds.

As much as there is no reason for not going on meds.

That the problem with a plateau: there is no trend: you can't decide

The 14% is definitively a benchmark. you hit that one, you go for meds and everything will go fine.

There are many posters in the forums... Very, very few report a non-response, so you should not be worried.

To get used to this one new item on your daily schedule (take yours meds without fault) you can train yourself. Kivexa is orange-yellow and very similar in size as a multivitamin, so buy yourself 2 different multivitamins and train yourself at gobbing these 2 pills without miss EVERY day.

Have you had the HLA **??57 test already ? (sorry can't recall the exact name)

It is a must do before starting Kivexa, it takes 3 weeks and doctor can not retain the results form you as this is information about your own personal genetics (not about the virus genome...), therefore you have legal access to it.

If I were you, I'd insist to get my CD8 data given to me.

Sometimes docs may refrain from giving it because, in as much as your CD4% is under range, the CD8%, conversely, will most likely be out of range as well (overrange)...
This is just mechanical (kind of) and make the patient over worried that he/she has 2 parameters out of range. No, they are paired, so it is not an additional reason to stress out.

as you have an appointment soon, you may ask your doctor if the VL trend (in the right direction) is something that you should want to explore

The chances that your immune system has found the way to contain the infection are slim, but, the immune system is working at it, generating many many various antibodies combinations randomly. The rule of thumb is that it takes about 18 months for that Darwinian Russian roulette to find one, which is fairly good news, and the sad news, is that in 18 months, the virus has plenty of time to generate a new mutant. So the arm race is, in general, not in favor of the patient. But, you might get lucky.

Hope this helps

Eric (not a doctor...)
NVP/ABC/3TC/... UD ; CD4 > 900; CD4/CD8 ~ 1.5   stock : 6 months (2013: FOTO= 5d. ON 2d. OFF ; 2014: Clin. Trial NCT02157311 = 4days ON, 3days OFF ; 2015: https://clinicaltrials.gov/ct2/show/NCT02157311 ; 2016: use of granted patent US9101633, 3 days ON, 4days OFF; 2017: added TDF, so NVP/TDF/ABC/3TC, once weekly

Offline leatherman

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Re: CD4% info and Trend after treatment
« Reply #10 on: November 05, 2013, 01:38:02 am »
Very, very few report a non-response, so you should not be worried.
exactly!
all these yrs, and I've never met or heard of one (just like the mythical oral sex transmission; but that's another thread LOL). Matter of fact, that's where the whole "Lazarus Effect" notion comes from. ART is so freaking magical that it brings back even those who were "mostly dead" (sorry, I watched Princess Bride the other day). Not only aren't there next to no non-responders; but those who were thought wouldn't even be able to make a response end up making a great response to the meds.

all this Gobbledy gook about percents and ratios and trends and cds 2,3,4,5,6,7,8 is all (good as it is - and it all is very good stuff eric!) is just a fancy way of saying "it takes meds to stop HIV. almost everyone has to break down and start taking them at some time. Taking them before you have AIDS is the better way to go. And the meds ain't so bad when all is said and done." ;)
leatherman (aka Michael)

We were standing all alone
You were leaning in to speak to me
Acting like a mover shaker
Dancing to Madonna then you kissed me
And I think about it all the time
- Darren Hayes, "Chained to You"

Offline new_2013

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Re: CD4% info and Trend after treatment
« Reply #11 on: November 05, 2013, 05:02:47 pm »
Thanks Eric, that reply and your previous posts are very specific and gives me additional perspective and understanding in this area. I appreciate the effort that time you have put into responding.

Thanks Leatherman also, I get your point re accept the meds and get on with it, am not trying to fight the inevitable, just understand it and personalise it a bit more at this stage.

Offline eric48

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Re: CD4% info and Trend after treatment
« Reply #12 on: November 06, 2013, 04:42:26 pm »
Keep us posted and stay healthy !

protect yourself and others.

I'll draw your VL trend if I have time this week end

Next week I have a blood draw and I hope the results will confirm a few things I have been working on recently

Cheers

Eric
NVP/ABC/3TC/... UD ; CD4 > 900; CD4/CD8 ~ 1.5   stock : 6 months (2013: FOTO= 5d. ON 2d. OFF ; 2014: Clin. Trial NCT02157311 = 4days ON, 3days OFF ; 2015: https://clinicaltrials.gov/ct2/show/NCT02157311 ; 2016: use of granted patent US9101633, 3 days ON, 4days OFF; 2017: added TDF, so NVP/TDF/ABC/3TC, once weekly

Offline leatherman

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Re: CD4% info and Trend after treatment
« Reply #13 on: November 06, 2013, 07:09:12 pm »
I'll draw your VL trend if I have time this week end
Graph Your Labs
http://www.aidsmeds.com/graphs/

it's how I've graphed my trends for the pix in my sig line. ;)
leatherman (aka Michael)

We were standing all alone
You were leaning in to speak to me
Acting like a mover shaker
Dancing to Madonna then you kissed me
And I think about it all the time
- Darren Hayes, "Chained to You"

Offline new_2013

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Re: CD4% info and Trend after treatment
« Reply #14 on: November 07, 2013, 07:38:10 pm »
Thanks guys, i'll keep in touch.  ;)

Offline eric48

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Re: CD4% info and Trend after treatment
« Reply #15 on: November 10, 2013, 11:33:06 am »
Such good data to play with! therefore, we should not spoil the party

This is an easy enough DIY, with a smartphone calculator, a piece of paper and a ruler; a spreadsheet would be handy since it has a build in linear regression capability (but you can do without); there may be some on-line tools as well.

In order to vizualize a trend, we need to plot against time... Plot what ?

On the X axis, I'd recommend time, in decimal month unit (a decimal month is the number of days elapsed divided by 30.5 or you can use 30);

Shortcut: 26th Apr is month 0; 09th Jul is month 2.42; 14th Oct is month 5.6; Jan 15 (2014) is 8.65

On the Y axis, I'd suggest to use the Log10 transform.
What is the Log10? In case you don't know or remember, I'll let you find out... As far as I am concerned, it is printed on my lab reports. Just ask, you'll find many people here able to explain you what this is.

Why Log10 transform before fitting? here again, just ask, you'll find many people here able to explain why... Hint: first chapter(s) of any book on regression

Shortcut:
VL : 98906 is Log10(VL) = 4.995
VL : 54748 is Log10(VL) = 4.738
VL : 29197 is Log10(VL) = 4.465

Pencil, paper, ruler (or use a pencil), draw and, then... comment.

Easy enough, right?

Need help? Just ask here and you'll find many people here able to help you

Have fun

Eric
NVP/ABC/3TC/... UD ; CD4 > 900; CD4/CD8 ~ 1.5   stock : 6 months (2013: FOTO= 5d. ON 2d. OFF ; 2014: Clin. Trial NCT02157311 = 4days ON, 3days OFF ; 2015: https://clinicaltrials.gov/ct2/show/NCT02157311 ; 2016: use of granted patent US9101633, 3 days ON, 4days OFF; 2017: added TDF, so NVP/TDF/ABC/3TC, once weekly

Offline eric48

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Re: CD4% info and Trend after treatment
« Reply #16 on: November 21, 2013, 05:09:02 pm »
Has any one tried to plot the graph? Eric
NVP/ABC/3TC/... UD ; CD4 > 900; CD4/CD8 ~ 1.5   stock : 6 months (2013: FOTO= 5d. ON 2d. OFF ; 2014: Clin. Trial NCT02157311 = 4days ON, 3days OFF ; 2015: https://clinicaltrials.gov/ct2/show/NCT02157311 ; 2016: use of granted patent US9101633, 3 days ON, 4days OFF; 2017: added TDF, so NVP/TDF/ABC/3TC, once weekly

 


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