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Author Topic: Undetectable with Declining CD4s -- Any Guidance?  (Read 3247 times)

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Offline PFOUR2013

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Undetectable with Declining CD4s -- Any Guidance?
« on: May 08, 2013, 08:28:03 PM »
Hello everyone!  I've read through these forums over the past few years but until this very moment have never posted anything.  First and foremost, I'd like to express my gratitude to everyone who contributes here -- While I have been a bit of a wallflower, these forums have helped me through some tough times and have certainly helped to educate me on living with HIV.

First a bit about myself... I was diagnosed positive a few years ago.  While my numbers at diagnosis were reasonable (CD4 427/37%, VL 11833), I elected to start treatment immediately.  For me, the pros far outweighed the cons.  Overall, my treatment has been very successful in suppressing my VL.  I originally started on Atripla but switched to Prezista/Truvada/Norvir due to the 'oh so enjoyable' fogginess that accompanied Atripla.

What brings me to the forums today is that my recent (past year) lab results seem to be showing a decline in CD4 counts and percentages despite a suppressed VL.  I recognize that my numbers will fluctuate and that I shouldn't jump to conclusions over one or two sets of labs.  However, after waiting 9-12 months to see how things would pan out, I am now starting to worry because (to me) the signs point to a downward trend.  I should point out that my total (absolute) lymphocyte counts and percentages have also been declining and have been either low or on the low end of normal (diagnosed with lymphopenia). 

I have been doing everything I can to stay healthy.  I eat well.  I exercise.  I get plenty of sleep.  And to boot, I have not missed a single dose of meds over the years.  I have been doing all that I can not to worry about my labs but I am starting to feel a bit defeated.

This prompts a few questions that perhaps you all can help me out with:

1. Am I reading too much into my labs?

2. Does anyone here have any experience with lymphopenia?  Outside of being HIV positive, my doctors and I have not been able to identify any other underlying cause.

3. Does anyone have any experiences they can share with declining CD4 counts and percentages despite VL suppression?  Could my doc and I be missing anything or trying anything else?

4. My doctor suggested that if my numbers continue to decline that we may consider switching meds.  However, with my VL being suppressed, I am having a hard time in seeing the benefit of doing this.  Your thoughts?

I certainly value the experience present throughout these forums.  Any information or guidance that you could offer would be appreciated.  Thanks.

Date    VL     CD4 CD4%
08/10 11833 427  37
11/10 15423 474  33
01/11 89       401  41
05/11 <20     473  40
08/11 <20     409  40
11/11 33       395  36
03/12 <20     579  40
06/12 <20     405  47
09/12 <20     384  44
02/13 <20     247  39
03/13 -----     246  37
04/13 <20     204  34

Offline weasel

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Re: Undetectable with Declining CD4s -- Any Guidance?
« Reply #1 on: May 09, 2013, 01:05:21 PM »

    Hi PFOUR2013   ,

                           I am on the same regime as you , have been on Prezista/Truvada/Norvir  for 9 ?  Months now . Was Reyetaz for 7-8 years ?

  I was horrified yesterday , My T-Cells have dropped another  70 points !
  I am now at 395  , I know that number looks good , but my % is 22 , so I have
102 good T-Cells , As I see it .

   I have been undetectable  from December 2004 .

  A few years ago I was up to  over A thousand T-Cells   .

 I really hope someone that knows what is up chimes in .

                                                   Weasel

 P.s. I am not a happy camper  :'( 

Edited to say 395 T-Cells  Not 465  :-[
« Last Edit: May 09, 2013, 01:20:53 PM by weasel »
" Live and let Live "

Offline Anqueetas

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Re: Undetectable with Declining CD4s -- Any Guidance?
« Reply #2 on: May 09, 2013, 01:35:21 PM »
In my opinion, I agree with your doctor about switching to a new medication. Sometime your body reaction to the medication could be unpredictable, in your case it could be in the form of lymphopenia. It would not hurt to try, you already do everything beside changing medication. Switching while maintaining UD viral load is very safe.

Good luck and let's us know how are you doing after switching medication.
ARS, hospitalized for very high fever-July 2011
diagnosed HIV positive - October 16 2011
CD4 460 19.5% VL 49000 - late October 2011
CD4 625 19.5% VL 50030 - January 2012
CD4 369 19% VL 69000 - March 2012
Start Sustiva+ Truvada - April 17 2012
CD4 524 24.5% VL UD - August 22 2012
Switch to Nevirapine+Truvada
CD4 490 26% VL UD - November 2012
CD4 539 29% VL UD - February 2013
CD4 621 28% VL UD - May 2013

Offline weasel

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Re: Undetectable with Declining CD4s -- Any Guidance?
« Reply #3 on: May 09, 2013, 02:49:14 PM »

   I am sorry PFOUR2013  ,

   I did not mean to hijack  your post !!!!

   I would delete it if I could !

                                          Weasel
" Live and let Live "

Offline newt

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Re: Undetectable with Declining CD4s -- Any Guidance?
« Reply #4 on: May 09, 2013, 03:12:44 PM »
I am interested to see what new meds you doc suggests. A combination with no nukes (specifically no tenofovir) may help.

Good luck

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

Offline PFOUR2013

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Re: Undetectable with Declining CD4s -- Any Guidance?
« Reply #5 on: May 09, 2013, 09:31:15 PM »
   I did not mean to hijack  your post !!!!

No worries at all -- I didn't feel like you were hijacking.  It certainly is helpful to hear other experiences.  My doc reviewed the research and consulted with pharmacists ultimately finding that nothing has been documented associating decreased lymphocytes with a prezista/truvada/norvir regimen.  Now that doesn't mean that it can't happen but given the lack of evidence, it also doesn't seem very probable to us.

Why did you switch from Reyetaz?  Best of luck with your next labs.  Hopefully this is just a little slump for both of us!

I am interested to see what new meds you doc suggests. A combination with no nukes (specifically no tenofovir) may help.

Good luck

- matt


We haven't really discussed the specifics yet.  My doc wants to wait another 3 months and take another look at my labs first.  A hematologist work up showed zinc levels on the low end of normal so I am testing out a daily zinc supplement first to see if that has any effect.

My doc did make reference to Stribild so that option doesn't get rid of the tenofovir.  I'd really like to stay on a 1x/day regimen so the options there are limited.  Why do you suspect removing tenofovir may help? 

Unfortunately I was only on Atripla for a few sets of labs.  My #'s were relatively stable during that time but then again, it is only a few data points so it might be a leap to draw any conclusions on the introduction of Prezista.

Thanks for the well wishes -- for now we are just playing the 3-month waiting game!

Offline weasel

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Re: Undetectable with Declining CD4s -- Any Guidance?
« Reply #6 on: May 09, 2013, 09:45:33 PM »


   
" Why did you switch from Reyetaz?  Best of luck with your next labs.  Hopefully this is just a little slump for both of us! "

  My liver was taking a dump !
   I spent three to four hours a day  on the toilet while taking Reyetaz !

    I also had a a year long orange glow  :o

    My husband always told people it was my Italian blood   ???

    I feel so much better !   Toilet paper is not first on the shopping list !

    I would like to say my liver feels better , but it does not  :(

     I'll let you know in three months how I am doing !

                                                            Carl
" Live and let Live "

Offline eric48

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Re: Undetectable with Declining CD4s -- Any Guidance?
« Reply #7 on: May 14, 2013, 08:36:54 PM »
Hi,

if you would draw you data:

03/12 <20     579  40
06/12 <20     405  47
09/12 <20     384  44

on a math. graph you would see that it fits a perfect parabolic decay

extrapolating the parabola goes to a plateau of ca. 198

the parabolic decay factor is 2. (which is quite good, mine is 1.56...)

Let me explain: it is not because your viral load is undetectable that is means that ALL your CD4s are virus free. the ultimate target of long term medication is that most (hopefully almost all, ultimately all) CD4s are virus free.

Therefore virus 'tainted' CD4s must go. (die). And if you have had no CD4 up-modulating illness (such as a flu or any MCH class 2 infection), then as the 'tainted' CD4s go down and the virus-free pool remains stable, and, then such a parabolic decay can be observed...

200 is your base of virus free CD4s and you immune system can from now on build up from that base.

200 virus free CD4 is certainly a better prospect than 200 virus infected CD4s

From now on it reasonably possible that the favorable built up takes place. That process may be slow since half life of virus free CD4 is 6 months and half life of CD8 is 9 months. Age over 50 will make it even slower

(your VL at around 10k shows that your dynamics are quite slow to start with)

If not, then of course, the meds are not fulfilling the job entirely ( meaning freeing the body from infected cells) and the most likely ones to have lost effectiveness are your NRTIs

I sympathize with the fact that this 200 number may create a bit of anxiety, but if they are good , 'healthy' CD4s and with such a good percentage (%) , they will do the job, and, I would recommend that you do not worry too much on it

(easy for me to say, as I am prone to anxiety myself)

wishing you well

Eric
« Last Edit: May 14, 2013, 08:39:56 PM by eric48 »

Offline Tamara

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Re: Undetectable with Declining CD4s -- Any Guidance?
« Reply #8 on: May 17, 2013, 02:28:02 PM »
I don't know if this would be much of a help but coming from someone as myself who have been positive since late 2005, I've always had a problem with my cd4 count..my Viral load has always been undetectable...I started talking to a friend of mine who has the same condition and he highly recommended that I start taking multi vitamins..since then my cd4 count has went up at least close to 500 from a 300 in the past 3 months.. and the only other medicine I take is atripla...hope this helps good luck :)

Offline PozGuy212

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Re: Undetectable with Declining CD4s -- Any Guidance?
« Reply #9 on: May 26, 2013, 04:53:06 AM »
Hopefully you can switch and aren't resistant to the other 1-a-day options like Complera or Stribild.

My count raised from 60-408 on Complera along with multivitamins, going to the gym, having a fast metabolism and fish oil capsules. I'm not perfect, I party a lot too!

I've stayed away from all protease inhibtors due to all the running-to-the-bathroom stories.

Good luck and hopefully this passes
March 2009 - Tested POZ
Aug 2012 - CD4 60 / VL 250K+
Started Complera
Nov 2012 - CD4 180 / VL about 2K
Feb 2013 - CD4 350 / Undetectable
May 2013 - CD4 400 / VL 50
Switched to Stribild

Offline PFOUR2013

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Re: Undetectable with Declining CD4s -- Any Guidance?
« Reply #10 on: May 31, 2013, 07:07:09 PM »
I started talking to a friend of mine who has the same condition and he highly recommended that I start taking multi vitamins..since then my cd4 count has went up at least close to 500 from a 300 in the past 3 months..

That's a pretty nice gain in your avg count.  I have been taking multivitamins for years now so your comment is a good reminder to never stop doing so!  My zinc levels were on the low end as well so the doc recommended taking a zinc supplement as well.  We'll see if there is much improvement come my next labs.  I decided to go for a consult with another ID doc.  I seem to be in a bit of a gray area on what (if anything) I should do so I figure another opinion wouldn't hurt.

My count raised from 60-408 on Complera along with multivitamins, going to the gym, having a fast metabolism and fish oil capsules.

I'm not to familiar with the benefits of fish oil but I have always heard good things.  Maybe it would be worth looking into as well.  Thanks!

Next labs aren't for another couple of months.  Hopefully the summertime shenanigans will help the time fly by!

Offline PFOUR2013

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Re: Undetectable with Declining CD4s -- Any Guidance?
« Reply #11 on: June 17, 2013, 06:41:33 PM »
I am interested to see what new meds you doc suggests. A combination with no nukes (specifically no tenofovir) may help.

I had a consult with another doc (2nd opinion) that also suggested the tenofovir may be the issue.  He suggested replacing Truvada with Epzicom and keeping the Prezista + Norvir.  It is still a nuke but might help.  Thoughts on this?  Outside of the risk for hypersensitivity, it seems like it is relatively well tolerated and effective (especially with UD VL to start).


Offline Ann

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Re: Undetectable with Declining CD4s -- Any Guidance?
« Reply #12 on: June 18, 2013, 07:39:44 AM »

Outside of the risk for hypersensitivity....


Epzicom contains abacavir and it's the abacavir (Brand Name Ziagen) that carries the hypersensitivity risk. However, there is a test that you should be given first before taking this med.

From the abacavir information page:

Approximately 5 percent of people who take Ziagen are allergic to it and can experience a "hypersensitivity reaction." This can be serious and may require that Ziagen therapy be stopped. A hypersensitivity reaction usually appears during the second week of therapy, but it can take as long as six weeks to notice any symptoms. The most common symptoms are fever and rash, followed by headaches, stomach upset, feeling tired, sore throat, cough, and shortness of breath. These symptoms usually get worse over time and it is important that you report them to your doctor immediately.

An inexpensive laboratory test is available to look for an inherited gene, called HLA-B*5701, that has been linked to the hypersensitivity reaction in HIV-positive people taking Ziagen. While not all people with this gene experience an allergic reaction while taking Ziagen, most do. In turn, if you are tested and found to have this gene, Ziagen (or other medications containing abacavir) should either be avoided or used with caution. If you and your doctor are thinking about starting Ziagen or another abacavir-containing medication for the first time, be sure to discuss this genetic test.
 
If your doctor tells you that you are allergic or are having a hypersensitivity reaction, you will be told to stop the drug. If you stop taking Ziagen because of these symptoms, you must not start the drug again, or start any drug that contains Ziagen (e.g. Trizivir or Epzicom). Some people who were allergic to the drug and restarted therapy saw their symptoms return immediately and became very ill.


Hope that helps.
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Offline PFOUR2013

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Re: Undetectable with Declining CD4s -- Any Guidance?
« Reply #13 on: June 20, 2013, 07:27:39 PM »
Thanks Ann!

I got a copy of my labs back and he did check for that (came back negative).  My CD4 count dropped again to 156 (from 204) and % dropped to 30 (from 34).  The continued decline is really frustrating and it becomes more and more difficult to stay optimistic.  I was a bit surprised that neither of my docs recommended Bactrim.  One of them said he wasn't too concerned with it particularly since my VL is UD.

Given all of this, I really feel like it is time to make a change.  Starting tomorrow, we are going to take the Truvada out and replace it with Epzicom.  I will update with (hopefully uplifting) results in a couple of months!

Offline eric48

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Re: Undetectable with Declining CD4s -- Any Guidance?
« Reply #14 on: June 30, 2013, 06:17:28 PM »
Hi,

depending the lab you are going to, the percentage precision is not too good (fast test) so I would allow a margin of error of 2% .
You earlier percentage might have been 32% but a reading of 34%
and this time percentage might have been 32 % (again) but reading is 30%

So by and large, this is pretty unchanged.

Because your CD4 count is calculated based on the percentage (they multioly total lymphocyte by percentage) and NOT the other way around (as it would seem 'natural' to a lot of people), when the number of lymphocyte is not to high, then the count is , at first look, drastically decreased.

In fact not;

As per my post way above, (6 weeks ago), I had put in perpective that you should be plateauing at a little below 200 for a while , then it will hopefully level off.

Most importnatly these are strong and healthy CD4s with a half life of several week/months. therefore not same as someone under active infection where most CD4s are infected and with a half life of 1  day

I take Epzicom. no complaints

Hope this helps

Eric

Offline PFOUR2013

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Re: Undetectable with Declining CD4s -- Any Guidance?
« Reply #15 on: July 10, 2013, 08:15:32 PM »
Hi Eric,

Thanks for all of your input -- thought I must admit I don't fully understand all of the math and decay discussion mentioned in your first post.  Have there been studies showing this?  Admittedly I haven't read much research at all but this isn't something I have come across.  Any additional info you have would be appreciated  :)

I went back for my follow-up with the doc after starting Epzicom.  So far no major issues.  He said it was likely still to early to see a difference (only been 2.5 weeks), but he did want to run my labs again to determine whether I should start taking Bactrim for the short term as well.  CD4 came back at 152 (33%) so largely no difference.  Hopefully this is my plateau point and things will increase from here.  I'll have another set drawn in 1-2 months to check again.

Offline 1in1000000

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Re: Undetectable with Declining CD4s -- Any Guidance?
« Reply #16 on: July 10, 2013, 09:18:08 PM »
Quote
Managing immunologic and clinical failures

Most immunologic failure follows virologic failure. The opposite situation where viral load is suppressed but the CD4 count fails to rise sometimes occurs. It is important to rule out laboratory and clerical error in processing the blood samples. Certain non-B subtypes are not accurately measured by the earlier generation of assays and alternative methodologies may need to be considered. Intercurrent illness and opportunistic infections may depress the CD4 count and have to be ruled out. Tenofovir (TDF) + didanosine (ddI) as a backbone of HAART is also known to have a negative impact on immunologic recovery.

In most cases, the phenomenon cannot be explained. Watchful follow-up is probably the only recourse while prophylactic treatment according to usual thresholds will have to observed. Most of these patients do well. Specific immunologic treatment such as IL-2 could be considered, but is overall clinical impact is unknown. Recently, certain antiretroviral combinations were found to be associated with a better immunologic recovery than others.13,14 Its relevance to this situation, however, is unclear.

On the other hand, immune reconstitution disease occasionally occurs in patients who have apparently responded to HAART, and yet deteriorates clinically (see Chapter 15). Immune reconstitution disease is not regarded as 'clinical' failure. It requires specific treatment and sometimes non-steroidal anti-inflammatory drugs and systemic steroids for symptomatic control. HAART is generally continued unless life-threatening disease occurs. True clinical failure develops rarely with virologic success and immunologic response. However, there is evidence that certain HIV-related complications are developing at higher CD4 strata in the HAART era. This is probably related to the fact that immunologic recovery from HIV-mediated damage is not complete despite viral suppression.



http://www.info.gov.hk/aids/pdf/g190htm/12.htm

Offline 1in1000000

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Re: Undetectable with Declining CD4s -- Any Guidance?
« Reply #17 on: July 10, 2013, 09:26:23 PM »
There is some evidence that thymus can be stimulated by the growth hormone.
You can ask you doctor.

Offline eric48

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Re: Undetectable with Declining CD4s -- Any Guidance?
« Reply #18 on: July 12, 2013, 05:01:04 AM »
If you have CD4 around 200 and % around 33% it means your total lymphocyte is around 600... This is low. The 'normal range' is : 1000 to 4000. mine are around 2000

Immunologic failure iss when total lymphocyte is normal and CD4 fails to go up.

have a look at your total lymphocyte before treatment, that may give you a hint.

More over lower than range lymphocyte may not be so much of a problem. only 2 to 5 % of total lymphocyte get out of lymph system into the blood. So you may still have a low % going into blood while having a normal quantity of lymphocites in the entire body.

the 33% is a good sign. what is your CD4/C8 ratio (or CD8%, if you wish) ?

Eric

Offline newt

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Re: Undetectable with Declining CD4s -- Any Guidance?
« Reply #19 on: July 12, 2013, 05:36:49 PM »
Agree with Eric - matt
"The object is to be a well patient, not a good patient"

Offline PFOUR2013

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Re: Undetectable with Declining CD4s -- Any Guidance?
« Reply #20 on: July 15, 2013, 10:03:41 AM »
Thanks guys.  My total lymphocyte numbers are low and have probably been cut in half over the past year.  My one doc thought my body just wasn't tolerating the combo I was on very well and was causing the overall decrease in lymphocytes (hence the switch from Truvada to Epzicom).  I saw a hematologist about 6 months ago but they didn't find anything too out of the ordinary (except a positive ANA which the rheumatologist declared insignificant after follow-up work).  Are you guys aware of anything non-HIV related that would be causing this?

Eric,

My last CD4/CD8 was 1.06. It has bounced around a bit but has been above 1 for the most part. 

Offline eric48

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Re: Undetectable with Declining CD4s -- Any Guidance?
« Reply #21 on: July 15, 2013, 11:48:17 AM »
I sympathize that a lower CD4 count may sound 'bad news', but, from what you're saying, I would not worry too much

a ratio > 1 is sometimes considered as a 'good news' in term of recovery, since a ratio <1 (and usual far below, mine WAS 0.25) is considered a hallmark of the disease, whereas > 1 is supposingly the 'normal' range.

There is no much 'clinical' benefit in terms of life expectancy, etc associated with a better ratio, but >1 is considered by some doctor as a plus and encouraging sign

I have put comment here:
http://forums.poz.com/index.php?topic=33062.msg569620#msg569620

BTW, that threat also provide some useful info about EPZICOM

Most likely your number will go up slow and one might say that is thanks to the switch to Epzicom. Hum... Switch or no switch your numbers would likely have gone up anyway.

BTW, the CD4 recovery is a 2 phase: there is an initial strong phase of about 150 (but bear in mind many people start low), then a plateau , then after another 6 m to 1 y. another raise of 150. I could find the reference for you, but, again, I would not worry

Epzicom seems a little less popular that Truvada, but, here again, there are pros and cons and most likely you will be fine with it (as do many, many, who do that switch...)

Good Luck Eric

« Last Edit: July 15, 2013, 12:00:20 PM by eric48 »

 


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