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Author Topic: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)  (Read 54624 times)

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Offline eric48

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  • Posts: 1,192
  • @HIVPharmaCure & tinyurl.com/HIVPharmaCure
08/09 : contamination (age 47)
09/09 : sero conversion
04/10 : tested +
04/10 : CD4: 440 CD4%: 18 CD8%: 61 VL: 65k (4.82 log)
05/10 : CD4: 535 CD4%: 16 CD8%: 63 VL: 52k (4.71 log)
05/10 : CD4: 453 CD4%: 20 CD8%: 55 VL: 68k (4.84 log)
06/10 : Viramune (Nevirapine) + Kivexa (Epzicom)

This regimen is listed in the US as an alternative (rather than preferred) and not for men with CD4 above 400 (and women with CD4 above 250)
In Europe it is in the recommended list with a warning for extra caution for men with CD4 above 400 (and women with CD4 above 250)

I took the HLA B*5701 test, the one that tells you if Abacavir should be avoided. I am negative : I can have it.

My readings are above 400 (440 to 535, depending...) therefore I was not expecting my HIV specialist to come up with this recommendation.

I have a number of concerns because of my age (getting close to 50), my blood sugar (was borderline before infection and now in the frank diabetes zone), low HDL (40 at conversion, now 35)
but no AIDS related events, no confection, I am even CMV neg ! - no enough kissing, I suppose) , no BMI issues (BMI at 22.5), no liver problems, etc. I walk or jog every non-rain day
One concern is brain/neurons issues in my family (Alzheimer, etc.)

Doctor says he likes the fact that one component (I think that is Abacavir) crosses the blood/brain barrier and therefore may have a protective effect

I looked into the available literature that compares various regimens and came to like this regimen better than others (due to my specific concerns).
Actually I like it a lot. For example it may protect the brain while not having the psycho effects of Efavirenz (I should emphasize  'may').
Seems to be a regimen you can stick with for a long time

Genotype says I have only one mutation (T215E) which forbids only AZT and d4T
All other options are open

PI s look a bit scary, not so much that they are, but because it seems to be jungle where the non specialist, like myself, can get lost
Atripla is the king  of the block these days and Raltegravir the new kid in town.
Both taken with Tenofovir (not so much of my liking)

My doctor is a long timer HIV specialist who runs a HIV clinic (somewhat specializing in MSM). He has seen a lot...
I asked him about adverse effects such a lipo and he raised his eyes, like he leaves that to odds
The way he is...
He seems to know that if I were asked to choose between damage to my brains or to my face, I would not sacrifice my being myself.
So he does not ask. The way he is...
 
My doc says this regimen was demoted for adverse reaction concerns but is likely to be promoted back to recommended next year or so.

He likes it, I love it: there is no hesitation here.

Special caution means extra liver markers analysis with my blood work and extra visit to the clinic (every 2 weeks for the first 10 weeks).
The doc is a big guy, very impressive, and very good at handling people's stress and anxiety
The extra visits are a bonus !...

Special caution means that I looked through the internet for people having used the same Viramune/Kivexa combo and did not find many threads

I like the idea that this regimen is a bit off-limits, a challenge custom designed just for me (although I am sure a lot of people have used it before me)

I am a bit concerned though and this is why I would like to hear from others who have used it. Please kindly share your experience with me and others

Many thanks in advance Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline J.R.E.

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  • Posts: 7,218
  • Joined Dec-2003 Living positive, since 1985.
Welcome Eric,

I am on the same regimen,  ( Viramune and Epzicom) I've been on this regimen since January of 04. I started meds October of 03, And it's still working for me. I am  58, and started meds just about 18 years into being diagnosed positive.  I also was taking Viread in that mix from around August 2004 until October of 09.  I dropped the Viread, and everything is still going well.



My numbers were a lot worse than yours when I started.  My t-cells were at 16, viral load @ 500,000 and a percentage around 4% ( in October of 2003.) My current percentage is 15% .  I am currently waiting on blood test results from June 2nd.


The highest my tcells have been, ( since starting treatment) were the high 380's.  I am currently in the low to mid 350's.

Viral load has been undetectable since November of 04 ( you can read this info on my signature at the bottom,  And my CBC, Chemical profile , and Amylase , are always within range,  However my cholesterol did take a jump up, after starting on meds, and I am on Simvastatin . I also have hypertension, so I am also on BP medication .


I deal with mild to moderate neuropathy, since starting on meds. Although I believe it's more Virus related.


I've never been on Protease Inhibitors.  When I started on Viramune, it was a two step process.  One viramune tablet a day for 14 days, then two tabs a day after that.  I take my viramune at 8:00 AM and 8:00 PM .  12 hours apart.  I take the Epzicom with my daytime dose of Viramune.

I get labs approximately every 3 months.  It has been this way since I started.

The doc will be checking you liver panel during the first few weeks, just to make sure your tolerating the Viramune well, and will be monitored regularly after that. A small percentage of people can also have a allergic reaction to the Ziagen portion of Epzicom.


Herman ( on this site)  is also on the same regimen.


Ray


EDITED FOR CORRECTION OF DATES



« Last Edit: June 13, 2010, 05:10:51 AM by J.R.E. »
Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline J.R.E.

  • Member
  • Posts: 7,218
  • Joined Dec-2003 Living positive, since 1985.



Doctor says he likes the fact that one component (I think that is Abacavir) crosses the blood/brain barrier and therefore may have a protective effect




I believe that's Viramune that crosses the blood brain barrier.

Ray
Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline J.R.E.

  • Member
  • Posts: 7,218
  • Joined Dec-2003 Living positive, since 1985.
Eric,

I am sure you've probably already read this info, but I will post it for you just in case :



VIRAMUNE :

http://www.aidsmeds.com/archive/Viramune_1616.shtml


Epzicom :


http://www.aidsmeds.com/archive/Epzicom_1580.shtml



Ray
Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline J.R.E.

  • Member
  • Posts: 7,218
  • Joined Dec-2003 Living positive, since 1985.


By the way,  your not contaminated !! Your infected with a virus, none of us are contaminated ! 


Ray
Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline eric48

  • Member
  • Posts: 1,192
  • @HIVPharmaCure & tinyurl.com/HIVPharmaCure
Many thanks Ray ! for the multiple and documented answer !

psychologically, I have a hard time with the entire thing and I feel encouraged by your posts.

I wish I could edit my post and correct the mistakes. Thanks for pointing them out.

Now, I can only post answers/reports on Sundays and today is Sunday.

I have noticed that a number of people who say that this combo works for them have been staying with it for a long time. I think one needs to get past these 6 to 10 first weeks.
I have tried to create conditions that, hopefully, will be favourable:
- I have managed to get all the critical work done before taking the meds
- I have a weekly visit to my now-retired family doctor, who kindly spends some time with me (helps with the stress, the crying, the fainting, ...)
- I'll be working from home for the next 6-10 weeks, so medication is not so much a burden to my work and to others
- I am on 'house-arrest' : no going out, no sex, no alcohol

I take Kivexa (Epzicom) at 11:00 PM (moving daily by 15 min. in order to place it earlier in the day) and Viramune at 8:00 (the first 2 weeks, Viramune is only once a day)

I take Kivexa before bed because I was told it can be rough. Moving it forward 15 min. a day would place it at 8:00 PM when it is time for me to start taking Viramune twice a day (therefore 8:00 AM- 8:00 PM)

The first 3 nights/days have been absolutely perfect (no nothing). I was feeling great and relieved

Last night I felt bold enough and:
- had a bit of wine
- took the pill at 10:30 PM and went to bed at 0:30

At 2:00 AM I was awaken by stomach discomfort and noticed a slight pain on the liver
Putting the nausea on a scale of 10 where 10 is the urge to throw up, I d say it was 2-3
Putting the liver sensitivity where 10 is, say, pain, like you ate way too much chocolate cake the day before, I'd say 3
Enough to keep me awake until 5:00 AM
Took my Viramune at 8:00 AM
Have been feeling so-so all day. Lying in sofa most of the day. Tension has been low all day : 100/60

I'll be more careful tonight in hope for a better night. These are pretty strong medicine after all...

Back in the days, people must have been weighting pros and cons, before deciding for the meds and may have stayed a long time with the viremia

Nowadays, it seems that the recommended strategy is to start early, which also means for some people starting with relatively high CD4 counts.

As stated earlier, I am starting this regimen with a CD4 higher than the cut-off value of 400 (for men, 250 for women). Controversial or not, I would not know...

In my case, it also meant starting 10 weeks after diagnosis. No much time to recover from shock

It is comforting to see you could recover to safer levels. It is good news to hear you can take Kivexa (Epzicom) at daytime. If things go well I wish I can do the same...

I'll report later (next Sunday?) about this (mild) liver pain and on going progress.

Cheers!
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline Inchlingblue

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Here is some info on Viramune:

http://www.hopkins-aids.edu/s.html?siteId=7151&publicationId=7147&navDepth=.%2F&queryString=viramune&image.x=0&image.y=0


You can make corrections on your posts within the first day (or two?) after posting by going to the post and clicking on "Modify." Of course if someone else has already mentioned the "mistake" in a subsequent post it's best to leave it as is so that it makes sense to others when reading the entire thread.

It sounds like you are approaching this very sanely; please keep us updated on your progress.

Offline BM

  • Member
  • Posts: 340
I was started on this combination and found it very easy to take, aside from an initial rash that passed without note. Unfortunately, I developed resistance to all three drugs quite quickly. Some doctors say you can take both tablets of Nevirapine at the same time, i.e. two tablets once a day. This is a non-standard dose and I suspect one of the factors that contributed to my developing quick resistance so I wouldn't recommend it if it is suggested to you (at least, not while your viral load is detectable). The year after my resistance developed, the British guidelines were updated to say that Nevirapine shouldn't be used if viral load is above 100,000 copies (my viral load was 1.1 million copies). Oh well!

Nevirapine passes the blood-brain barrier too.

BM
« Last Edit: June 13, 2010, 03:28:26 PM by BM »

Offline J.R.E.

  • Member
  • Posts: 7,218
  • Joined Dec-2003 Living positive, since 1985.
Quote from: Inchlingblue link=topic=33062.msg407523#msg407523

It sounds like you are approaching this very sanely; please keep us updated on your progress.
[/quote


I also agree that you seem to be handling this well, considering your a relatively new to all this.  One step at a time, is what I say.


Keep us updated Eric, And don't hesitate to contact your doctor, if you feel things aren't going well.


Take care of yourself-------Ray

« Last Edit: June 14, 2010, 05:22:34 AM by J.R.E. »
Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline eric48

  • Member
  • Posts: 1,192
  • @HIVPharmaCure & tinyurl.com/HIVPharmaCure
On Sunday, I was not feeling too well... My stomach a bit uncomfortable (although nothing serious)
I was a bit worried about taking Kivexa when something crossed my mind:
- my doctor in a previous visit had expressed concerns about my not drinking enough water (see my blood sugar issues)
- I had read one post mentioning that increasing water intake could help
- I had noticed that my weight had dropped overnight by 0.9 kG - 1.7 lb : that could be a bit of dehydratation

I theorised that ARVs are changing my metabolism and more water is needed.
I did take much more water (1.5 litre) in the few hours left before Kivexa time
I felt better about taking my Kivexa pill and went to bed full of hope. But then, suddenly, the alarm rang...

It was 8:00 AM. I had fallen sound asleep and had a very good night

I can not say for sure that the water did the trick, but I kept very careful the entire week about it.

I also think that Kivexa makes me wake up in the middle of the night or wake up early. I was feeling the lack of sleep.
Therefore on Friday night I took half a pill of Unisom (an over-the-counter sleeping pill that contains Doxylamine succinate) I very rarely use it (only when I have jet lag problems) and most likely a quarter of a pill would have been enough to ensure a good, undisturbed, night sleep.
As a result I slept until noon (took my pill on time at 8:00, though) and again till 4 :00 PM. This is more than I would expect from a 1/2 pill of unisom and indeed I must have had a tiredness that went unnoticed and is now behind me.

Physically, the entire week went OK. a bit constipated, nothing worth mentioning. No rash, no vomiting, etc. The Kivexa drug information mentions that side effects usually occurs from the second week of taking the meds.
I am now entering this 'dangerous' zone.

Since the diagnosis (therefore 10 weeks before starting the meds) I suffer from brain effects that scare the shit out of me.
When it occurs, I feel like my brain is compressed in a helmet and floating on springs. It does not go away with the usual pain killers
Most times it happens when I am stuck in my though because I have tumbled against the virus thing. (for example, writing these lines triggers it...). This was not happening before the diagnosis and had some occurrences before initiating the meds.
To me, this sounds like self-inflicted stress-induced, not drugs nor virus related, but it leaves me a deep despair.
I have fainted a lot (5 times in 10 weeks) and cried a lot too. I have less crying now, but (consequently?) more of the headache thing

I had expressed concerns about a potential weakness there to my doctor (obesity/diabetes/Alzheimer in my family)
When I asked him why he chose a regimen that is normally NOT recommended in my case (it is written in the US guidelines that it is NOT to be prescribed to men with cd4 over 400)
he said that he was interested in the potential protection for the brain and central nervous system.

This matter is still being debated and right or wrong I do not know if there is yet a final answer.

Nonetheless this link here below shows that ALL of my regimen compounds are crossing the Blood/brain barrier.

http://www.thebody.com/content/content/art54535.html?getPage=4

So not just Nevirapine and Abacavir (as discussed above) but also 3TC (to a lesser extend)


Whether this is a good thing or not I do not know, But I feel very happy (privileged?) that he had listened to my concerns and that we are doing something about it.

This is why I am so anxious to see me pass the 6 to 10 first initiation weeks.
I suffer from an immense sense of guilt and stupidity about my infection and a failure to carry on a combo that I came to like would only add to it.

After now 10 days in the meds, a bit of stomach/liver discomfort that has apparently and so far disappeared, I am more upbeat

Reading the forums has been very helpful and I have the feeling that this regimen, once successful, can be carried on for many years.

There has just been a new publication on pubmed that comforts this impression.
http://www.ncbi.nlm.nih.gov/pubmed/20542847

It concludes:
NVP demonstrates sustained efficacy and good safety and is very convenient to use as reflected by a high rate of persistency.

I must deeply thank those who are posting on this thread about their experience with this combo. There are so many posts about Atripla that I felt isolated
All advises are welcome. If things go fine, I hope it will make it easier for me to come to terms with my fears and guilt.

BM, Rey, Inchlingblue : Thanks for the advises and support

I intend to take Viramune with the twice a day dosage, as this dosage has now been proven better for treatment-naives.
On the long run, and if we ever get there, I will consider take Kivexa in the morning and then, I might consider Viramune as a once a day dosage along with the Kivexa.

Next week, Wed., I'll get my blood work and will start taking Viramune twice a day. Hopefully I should be able to post lab results soon. My current general feeling of well being makes me hopeful.

I'll keep my fingers crossed
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline Inchlingblue

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Since the diagnosis (therefore 10 weeks before starting the meds) I suffer from brain effects that scare the shit out of me.
When it occurs, I feel like my brain is compressed in a helmet and floating on springs. It does not go away with the usual pain killers
Most times it happens when I am stuck in my though because I have tumbled against the virus thing. (for example, writing these lines triggers it...). This was not happening before the diagnosis and had some occurrences before initiating the meds.
To me, this sounds like self-inflicted stress-induced, not drugs nor virus related, but it leaves me a deep despair.
I have fainted a lot (5 times in 10 weeks) and cried a lot too. I have less crying now, but (consequently?) more of the headache thing


I'm not on your same combo but I was getting very strong headaches before starting the HIV meds and they pretty much went away once I was on the meds and became undetectable. I think it was caused by the HIV itself.

Offline J.R.E.

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  • Posts: 7,218
  • Joined Dec-2003 Living positive, since 1985.
Eric,


I also had some of these headaches after starting on meds.  It wasn't a daily thing, but they were severe enough at times, that I would be forced to lie down. I very seldom if ever get headaches any more. But I never fainted.

My working hours are flip-flopped from everyone elso.  I work the 11:00 PM to 7:00 shift. I sleep in the day and awake at night.

I was taking epzicom at 8:00 at night, but found it to be a little intense.  I switch it to 8:00 AM, and I usually go to sleep around 11:00 in the morning.

Yes, Make sure to drink plenty of water !!  You can also have meals with these meds, your not restricted to food intake on Viramune or Epzicom, unlike Atripla. So, try having some food when you take your meds. It might help to ease the stomach situation.



Ray
Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline BM

  • Member
  • Posts: 340
Hi eric48,
            If your stomach discomfort persists, it could be a sign of acid reflux, which is something I (and quite a few others) experienced when starting meds. Mention it to your doctor.

BM

Offline eric48

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  • Posts: 1,192
  • @HIVPharmaCure & tinyurl.com/HIVPharmaCure
Still alive and kicking !!!


trauma induced symptoms
*****************************

I have fainted in public and fallen into tears quite a few times now (including before the meds).
This creates a stress that reflects on my stomach/sleep etc.
On Wed. after going to the lab for the blood draw, I was feeling so bad that I would not be able to drive back home
I paid an unscheduled visit to my doctor (a few blocs away)
We did not have the lab results yet but physical examination was OK, so he told me to call to confirm if I could move forward, that is take Viramune  twice a day.
I said that I had the intention to do so and he kindly but firmly said that I should seek his approval before so doing.

While I knew Viramune should be introduced in a 2 steps process and needs to be monitored, I did not know that I should get doctor's thumbs up before continuing.
Considering that step 2 should NOT be delayed any further than the initial 14 days, it means that one should be very strict in having blood drawn on Day 13 and have a visit to the doctor on day Day 13 or 14
(my lab said they could give the results in a few hours, but I would not know if this is true for all labs).
My blood work had happened on Day 13...

I reported all my stomach/stress problem. He said that this is most likely of psychic cause and referred me to the clinic's psychologist and also prescribed Prazepam (N05BA11)
As of today, I have made an appointment with the psychologist, but I have not (and intend to avoid) bought the anxiolytic

I called the doctor on Day14 and he told me on the phone that the lab results are excellent and told me to carry on.

Referring to my post traumatic stress disorders he said that:
We will have to find the keys to carry on

Yes Doctor, I am working on finding these keys !!!

There was something in his voice that told me he is very confident this will work and we should carry on ...
Looking at the lab results, I also had a hunch that this is working. I will not speculate uselessly right now, but will share my thoughts once the real lab results (CD4 and VL) are available (in 2 weeks) 

Strangely enough, from the very moment I had entered the clinic for this unannounced visit, most , if not all, discomfort was gone
Upon starting viramune step 2, I felt safe, secure and have been feeling super since then.

Last Saturday night (Day 16) , I have had an episode that mirrors that of Day 4 : no sleep at all, constipation and feeling down the entire Sunday (today)

I have now learned a few things about of these 'side effects' on me:
- they are very bearable (so far)
- they will fade with time
- Stress/shock induced should not be mistaken with meds induced
- something really positive is going on inside my body


 Lab results
************
14 days after starting Viramune I have got my first follow up lab results. CD4 and VL have not been measured at this time, they will be in 2 weeks.
doctor is checking my liver enzymes:
GGT Reference ranges: 8-61
current (06/23/10) : 20  (baseline : 05/03/10) 15
SGOT (ASAT)
Reference ranges: Female 6 - 34 Male 8 - 40 IU/L
current (06/23/10) : 29  (baseline : 05/03/10) 27
SGPT (ALAT)
Reference ranges: 10 - 50 IU/L
current (06/23/10) : 18  (baseline : 05/03/10) 22
PAL
Reference ranges: 40 - 129 IU/L
current (06/23/10) : 52  (baseline : 05/03/10) 57

Reference ranges may vary upon test labs, gender, etc

CD4 CD4% and VL not measured
Lymphocytes are 3100 /mm3

I addition to info available here, I have found this site very usefull:
http://www.viramune.com/

Cheers

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Reporting July 4

I know I was getting sick with all the stress and shock recovery... I finally allowed myself the anxiolitic.

Since then, every thing went smooth, smooth, smooth (a bit sleepy with that medication)

Went to the pharmacy and did not faint (for the first time since...)
Went to the Lab and  did not faint nor cry (for the first time since...)

Tomorrow is my scheduled visit to the Doctor and I cross my fingers (there is always a bit of commotion around this 'older' guy crying and fainting like a Diva, which is something I hate about this situation)

Hopefully the results will be good...

Cheers

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline Inchlingblue

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Tomorrow is my scheduled visit to the Doctor and I cross my fingers (there is always a bit of commotion around this 'older' guy crying and fainting like a Diva, which is something I hate about this situation)


Your choice of wording here makes this rather funny ;)

Sounds like you're doing great, keep it up.

Which anxiolitic by the way?


Offline eric48

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Thanks!

This is true, I am finally doing real fine. All this stomach discomfort and headaches are gone.

I am quite sure that they were stressed induced.

Doctor prescribed Prazepam (goggle for :N05BA11 should you need more info). He said 10 mg in the morning and 10 mg at night. I'll do it for a few days then I will restrict to the Pharmacy/Lab/Clinic days.
(actually, I already take only one 10mg pill a day)

Can you believe that I had to walk all the way around the block where my Pharmacists is because the mere fact of walking past it would throw me in tears (and ruin the day...) ?

Believe it or not I had to postpone lab visits because I fainted on the way !!! And I am (almost) fifty !
(Doc says the younger generation takes it easier, I guess because they have NO IDEA what is was back then...)

Test and treat, they say... Easier said than done !

But you are right, the shock seems behind me now, and I must admit reading this forum has helped a lot

Thanks!

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline Inchlingblue

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One thing you should keep in perspective, Eric, is that you live in a country where you have access to treatments and medications as part of a national health insurance pool. Even in the US there are many people who don't have access to meds and to insurance, not to mention the deplorable conditions in the developing world for anyone with any chronic condition.

When you walk by that pharmacist you should be crying tears of joy.

Offline J.R.E.

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Hello Eric,

Glad to hear, that things are going better for you, and that the stomach and headache discomforts are gone. Stress can really wreak havoc on us, so it's best to try to manage this as best as possible.



Hang in there----Ray


Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline eric48

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Thanks guys ! Lab results came out SUPER. I'm on the road. Will post them all on Sunday.

Cheers!

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline J.R.E.

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Thanks guys ! Lab results came out SUPER. I'm on the road. Will post them all on Sunday.

Cheers!

Eric


That's great to hear !!


Ray
Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline eric48

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TEARS of JOY: Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #21 on: July 11, 2010, 10:05:39 AM »
For this last week, I have been doing absolutely fine !
No nothing ... no stomach uneasiness and most importantly no brain/mind issues

As reported before, I thing that the fog or helmet feeling that I had was stress induced.

Doc asked me to take 2 times a day 10 mg of Prazepam. Says it is a baby dose. Makes me sleepy.
Actually I only take 1/4 of the pills and now only when I  feel the need for it. I haven't had to take it for the last 48 h.

Knowing that this anxiolitic does marvel on me (and cost less than 5 bucks for 50 pills) I wonder why he waited that long to prescribe it.
I make this note for the new comer: do not hesitate to ask your doctor. stress induced brain pain could be misinterpreted for meds SE (by patient, at least)

DO NOT DRIVE when using these !!! The baby dose (as my doc puts it) makes me sleepy, and I was carefully NOT to take the pill on that morning I took the car for a long drive
my previous pill intake was 14 hours before. Nonetheless, while driving, I very suddenly went asleep and car drifted to the ditch. Apparently went in contact with the safety rail
with a very small angle. Front wheel dub exploded, that woke me up (sure did !!!) and I took control again.

Not even a scratch on the paint ! I will have to change that dub ($20) and that it.

This is why I am now on a 1/4 dose and only when needed (and no driving!). Doc says this anxiolitic is the mildest you can have and may have varying effects on people, but that some people take as many as 10 a day without problems.

I would not know if my specifics are just myself, the combination of the anxiolitic and ARVs, or just a result of the mental exhaustion I must be suffering.

This long note just to say that I could have died last week from... a mere car accident !...
I still recommend to mention use of a stress relief medication to doctors when just diagnosed or when starting the meds.
Just be Extra Carefull.

Tears of joy
************

Now I have a new problem : tears of joy !!! sudden outbursts (only when by myself...) (Boy, I even did not know this 50 year old guy could be sooo sissy...)

And there, believe me I take no action against these !

I already sensed the lab results would be good and I had even anticipated a good CD4 reading.
(due to my age, I had told myself to be modest in my expectations, but still...)

I was not expecting this:

Lab results
***********
as of July 5 2010 (under brackets are the latest known values most of them as of May 28 of beg. of May 2010) Meds started June 9

CD4 650 !!! (440)
CD4% 29% !! (20%)
VL: 600   ! (that is 2.78 log vs 68600 - 4.84 log)

That a 2.06 log decline in less than 30 days! No wonder I was tired !
(assuming 5 liters of blood that's 340 Million virions KILLED - GONE - KAPUTT)

I could not have hoped for better! Doc was kind of apologetic for the modest rise in CD4, saying that I have been on half dose of viramune for the first 15 days...

Doc! Are you KIDDDDING ??? that is a 210 increase (about 50 %) coming with a comfortable restoration of CD4% (+ 50% of the percentage) as a bonus.

May be that is because it did not see me burst in tears (again... and he is my favorite victim at a rate of 4-5 times/visit - but never fainted there)
And for a cause : I KNEW it was working on me... (and I had a 1/4 pill anxiolitic before too...)

It was only when I reached home that I started realising that the results are good because the other values are very good too!

Liver:
ASAT 27 (29);
ALAT 18 (18)
CCT  23 (20)

Cholesterol cranked UP! (as expected...) but importantly the GOOD HDL went way up!
HDL 0.53 (0.35) (this is my best reading EVER ! 40 was my usual before HIV)
LDL 1.38 (1.11)
Total Cholesterol  2.07 g/l (1.63)
Triglycerides 0.80 g/l  (0.65)

Fasting glucose
0.93 g/l (1.53 before the meds, 1.05 2 weeks into the meds)(this is my best reading EVER ! 1.05 was my usual before HIV)
Glycated hemoglobin (HbA1c) 5.8 % (6.4)

(side note: I've put on some weight: 1 kg, but, I can work on this...)

CHECKPOINTS
***********
Here, targets are
- decrease of 1 log after one month (PASSED!)
- decrease of 2 log and/or < 400 after 3 months
- <50 after 6 months

OK... I know I should be carefull about expectations as one never knows what kind of tricks the virus may have in store

Doc asked what I think about Side effects. Said that week 2 was a bit rough but all this is behind me now ...
Not so fast, he said... Allergic reaction may still occurs and I have to wait another 6 weeks to claim victory (over potential adverse reaction to viramune or Abacavir)
but, yes, I am 2/3 done... And another 6 weeks to go...

The CD4 increase: I knew it !
*****************************
(kind of...)
At Week # 2 I had an intermediate lab results that did not have CD4 nor VL ...
Nonetheless, reading through this forum and posted data, I have noticed that in  *** most*** cases (but not all, I must admit)
CD4 %, which is usually a less fluctuating value, would at least remain stable (read: will not decrease) right after the initiation
So I took my latest CD4% (20%) and the total lymphocytes reading at Week #2 (which I had: 3100), multiply and got a prospective value of 620 (assuming CD4% would not change)
I think the assumption that CD4% does not change is valid for a a short range of time, but hey, it gave me a number that gave me hope and relaxed my stress !!!

My Doc says he is not too much into maths and stuff, and as long as I this had made me feel better, then it is fine with him...
(I sure think that me not bursting into tears as usual was already good enough for him)

Future plans
************
I take viramune at 7:00 AM and 7:00 PM , then Kivexa at 22:00.
Doc says I am over doing it : I could take Kivexa at same time as Viramune ... Well, doc, see, I do not want to stress my liver too much.
Even if it is an overkill, it does not bother me that much (at least in the beginning)
In 6 weeks, if I pass the SE danger zone, then I'll try Kivexa in the morning (some people have had a hard time with this)
Then see how it works for me.
On the long run, I am concerned that I might forget a Kivexa dose, go to sleep and then it is too late...
If you miss it in the morning and realize it soon enough, you still have time to do something about it.
2 takes a day does not bother me much. What I fear is a tiring day at work, a glass of wine and... falling sound asleep in the couch...

Doc said that if this works for me, after a while we could even take the 2 viramune in the morning (We ?, ???, ?????????)
He said that the Viramune manufacturer is already working on a once a day pill.

We ???  (some more TEARS of JOY)
******************************

Doc, do you realize you took care of me, gave me a combo that is NOT the most prescribed (Atripla) (though I admit your choice suits my concerns)
Doc, do you realize how much I admire you, for your work, for your calm, understanding of people, your deep and comforting voice ?
Doc, do you realize I am scared to death (and of...) with the SE (that did not come so far) ?
Doc, do you realize I talk to you all night long ?
Doc, do you realize you just said that we could take all those pills, all at one time, at 7:00 AM, then get back to sleep for a little while and forget about all this and start the day as usual?

Doc, do you realize you just said WE ... Like... like... See what I mean ? ... WE (like in ... ) ???

Oh Boy !!!, I had to refrain some more TEARS of JOY and rush out of the clinic ...

I am Soooooooo confused and sooooooo happy at the same time !!!!

Stay tuned

Cheers!

Eric
« Last Edit: July 11, 2010, 10:09:36 AM by eric48 »
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline Inchlingblue

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Eric, you're doing great, congratulations.

Offline eric48

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Hi,

This week the good news is that there are no news...

Some days, I 've been tired... I think it is exhaustion resulting from stress. Actually, I am taking the anxiolitic far less than the prescribed dose (I take 1/4 of a pill, only when needed, whereas doctor prescribed 2 x /day)
I think I may have taken 1/4 of a pill only twice this past week. Still does the trick !!!

Looking back, I think that most of what I had described above was due to stress. This is important to note because there are not that many patient posts on forums or the Internet about this combo. I guess that is because people usually have nothing to complain about it.

The new US guidelines says that Viramune should not be given to people with higher CD4 (>400 for man and 250 for women). So people, who, like myself, have been offered this combo at 400+ are kind of worried.

As for myself, I keep my fingers crossed until the end of the initial observation period (10 weeks); in my case, end of Aug. 2010. But so far, so good ... Week 2 and 3 have been a very little tough, but no big deal. Nothing of interest since.

Someone, who was concerned with Viramune at 400+ has posted on TheBody:

http://www.thebody.com/Forums/AIDS/SideEffects/Current/Q209607.html

(Viramune + Truvada lypodystrophy & other side effects)


I will gather some of the information I had collected when I was asking myself the same question as he does and will post next week.

It is kind of hard to say, but, reading through patients opinions, I've almost never seen any complaints about Viramune whereas the number of people complaining about brain SE with Efavirenz seem to be quite many (some people say as high as 20%)
So, yes, Viramune (and Kivexa, in my combo, alike) require close monitoring at the initiation (because of allergic reaction of the liver), but I guess that once you've passed that, then, it is OK (I hope...)

I hope to gather your user's experience and share it with others ...

Cheers

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline heartforyou

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Hi Eric,

Thnx for the condolences. Even now there is always time to help out, so... here is my experience.
I have been on this combo, + Viread since about 4 or 5 years now.
I am extremely happy with it. It has been the easiest combo to take for me, once daily.

I do not have any side effects  at all.
I may experience a light neuropathy occasionally, but that only occurs if I have  not had enough sleep or I wake up in the nigth. This occurs vere rarely though.

I once was at  7 CD4 count  and a viral load of millions.
I am now undetecable since 1996 and my t count is currently at 750, the highest ever was 950.

Now, consider yourself lucky to be on it... I have been on MANY other combos, of which the one with truvada was sheer horror. Many others gave me nausea, liver or kidney problems and fatigue. This one is just .... a dream come through for me.

I surely hope you can stay on it...

xx hermie
Diagnosed in 1987 and still kicking
Viread, Kivexa (Epzicom),Viramune once daily

Happiness is the freedom of breathing fresh air every day.

Offline J.R.E.

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Hi Eric,


I have been on this combo, + Viread since about 4 or 5 years now.


xx hermie


Hello Eric,


I thought Herman would chime in , when he read this thread.  He was the one I mentioned in my first response to you in this thread.  I want to add, that I was also on Viread, along with Viramune and Epzicom.  I dropped the Viread around October of 09, and so far so good.



Ray
Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline eric48

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hi guys,

Many thanks for your comments and encouragements !

This weeks I have been working on collecting some articles about hepatotoxicity due to Viramune (nevirapine) in order to document my thoughts, especially with regards to the message left by someone on TheBody (see my post above)

See, I was offered this combo eventhough I was CD4 > 400 (and male). Guidelines for the Use of Antiretroviral Adults and Adolescents; by DHHS, dec 2009, says no, no, no... So like this person who had posted on thebody I was highly surprised

Your opinion about this combo has been (and still is ) very dear to me during this initiation period. Collecting information, I found reports that contradict the reports on which DHHS based their limitations.

I will therefore put a bit more time into it before I write any further.

As for myself, this week's report is going to be short:
- I have to go to bed early, leave early for blood work tomorrow. It is going to be more fun when we have the results...
- my general status is improving...

Until last week the only  subject of concerns where:
1- I am constipated
2- I sometimes have a fog effect in the brain (this immediately makes me very worried and sad)
3- I sometimes have a heat effect in the back of the neck (flu-like, duration 2-3 hours)

1 is since I take the meds (never happened before); 2 is since I have been diagnosed (never happened before); 3 dates from way back and I know I had this before I got diagnosed, so may be its the virus that does that
2 and 3 are typically every other day, always starting around 4 PM, lasting 2-3 hours. This is bearable but since it is recurring, I found it very depressing.

I have finally resorted to take the anxiolitic once a day (1/4 of a pill max per day instead of prescribed 2 pills a day). I think it helps!

I suspect there is some kind of interaction between the anxiolitic and the meds because the only day where I took it at my Kivexa time (10 PM), I had a bad night (nausea, tachycardia)
I now take the anxiolitic at 4 PM. and for the last 5 days I have not had any of the 2 and 3 effects.

In other words, the last 5 days, my only (little) problem has been constipation. All other effects have receded. I will carry on with the anxiolitic for a while and then we will see.

I am very hopefully. I am very anxious to pass these 10 weeks initiation (I am at week 5 or is it already 6?). Like Hermann said, I would very much like that this combo works for me, because from all I have read, while this combo may not be for everyone (hepatotoxicity in a very few % of patients), if you can have it seems to been an easy enough combo.

Once again many thanks for your feedback !

Next week post will be more fun as we are going to have new labs !!!

I must go... It is time for Kivexa (and teletubbies...)

Cheers
Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Good news ? Bad News ? New labs. VL going up

Hi,

I got my lab results of Monday July 26

on the goods news: CD4 and CD4 % still increasing:
********************************************************
CD4 : 800 (last month 650 - base line 450)
CD4% : 32 % (last month 29% - baseline 20%)
CD4/CD8 ratio : 0.7 (last month 0.59
CD8% 46 % (base in the sixties)
Fasting glucose 0.81 (lowest EVER)

On the NOT SO GOOD
**************************
VL is slightly up (700 vs 600 last month)
Cholesterol (all figures) are up another 10%

At first, I was so happy with the good immunologic response, that I did not noticed the VL slightly up ...

Now, I am left in anxiety. Next meeting with doc is Thursday 29. Will see what he says. In the meantime, I still have the anxiolitic to help me through.

I t is not that bad, if the trend is not confirmed on next lab (next month...). Boy , I would hate some king of virologic failure!!! Despear....

I do not know what to think.................

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline Inchlingblue

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Don't get stressed out. This does not necessarily mean resistance.

If you've been totally adherent then chances are it's nothing, there is a margin of error when measuring these things.

Offline eric48

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Thanks Buddy !

I try to cool down and be rational. I know I am panicking over details and it does me worse than good. My virus already has one mutation (although not limiting my choices too much) but still... I just can't stop thinking that
it is an experienced virus. Because my virus is resistant to older meds (AZT and d4T) I can't stop myself thinking that, in the transmission history, there is someone who was under these older meds and transmitted the virus.
Someone who KNEW he or she was infected and somehow carelessly passed it on. I wish I would not have to say so but this simple thought fills me with hater or rage, and then I know the brain frog might come (I successfully keep it under control thanks to the anxiolitic)

I have a (difficult) anniversary to pass and was looking forward to a bottle of champagne for, you see..., good results.

Cd4 at 800 should be more than enough to be happy with. It is just that I can't suppress the idea that my virus could turn out more tricky than I thought. Spoils the celebration, kind of...

Also found out a significant deficiency in Vitamin D, but that should be expected and I think they have something for it.

Vitamin D3 is at 11 ng/ml which is very low. May be the reason why I feel exhausted...

You are very right... I should just cool down... I wish I could. Good to know you're around

Cheers with a grin but Cheers nonetheless !

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #30 on: August 01, 2010, 05:14:58 PM »
Hi,

I visited my doctor on Th. July 29 2010. and expressed my concerns about VL going slightly up. He said that VL measured at that stage was not very relevant.

I had it measured because I needed the CD4 count for some other reason, so while I was at it... Could be an outlier... There is noway to know. Or is there ?

I came across a very recent article where the researchers have tried to find a reasonably good substitute for VL measurement in economically challenged area, where VL is not readily available for all.

http://www.aidsrestherapy.com/content/7/1/25:

Identifying individuals with virologic failure after initiating effective antiretroviral therapy: The surprising value of mean corpuscular hemoglobin in a cross-sectional study

The full article is available for free

While WHO considers that a good immunologic response is a good marker of virologic response, they found out that it, alone, is not a good enough substitute/predictor.

The surprising finding was that another readily available set of data, when combined with the immunologic response, provides a pretty good model.

The amount of Hemoglobin in RED cells, that we can imagine being how much red a red cell is, when combined with the immunologic response in a simple calculation, is a pretty good substitute to virologic response  measurement (using VL)

The researchers themselves seem to be pretty much surprised with their findings

In addition to current CD4 count and cd4%, you only need to know MCH (and, of course, values at baseline). This value is usually reported in basic lab reports (I found it in mines)

I made my self a small Excel sheet, which I'd be happy to post if I knew how...

Inputs are: Baseline_MCH ; Current_MCH ; Baseline_CD4% ; current_CD4% ; current_CD4 (count) (MCH = mean corpuscular hemoglobin)

You calculate:

A = 7.27
B = 0.19 x Current_MCH
C = 0.22 x (Current_MCH - Baseline_MCH)
D = 0.32 x current_CD4 / 100  (you must divide by a 100...)
E = 0.05 x (current_CD4% - Baseline_CD4% )

Then calculate F = A - B - C - D - E (simple substractions...).
The probability for intermediate virologic poor response is then P = 1 / (1 + e ( F * -1))

F is likely to be a negative number, therefore have to be multiplied by -1. e () being the neperien exponentiation.

I have applied to my numbers:

As of July 5 (therefore 4 weeks into the meds)
Baseline_MCH = 30.8
Current_MCH = 32
Baseline_CD4% =  20
current_CD4% = 29
current_CD4 = 650

Yields a probability of poorer virologic response of 33% (as defined as failure be at VL < 500 after 4 months)

As of July 26 (therefore 7 weeks into the meds)
Baseline_MCH = 30.8
Current_MCH = 33,1
Baseline_CD4% =  20
current_CD4% = 32
current_CD4 = 800

Yields a probability of poorer virologic response of 19%

In other words, things may have improved more than I originally thought...

The lowdown is that I am using the J. Hopkins formula as a predictor, whereas it is not intended to be. (it is intended to be a substitute in case VL can not be measured at intermediate end point of 4 months)

And odds are just what they are... odds. Also, I think that the findings of the researchers at J. Hopkins are , as they state: surprising !

Still going through the above calculation cheered me up and I have had a much better week.  

In fact, on the SE, nothing to report except a bit of constipation.

So, ... so far, so good

Cheers!

Eric
« Last Edit: August 01, 2010, 06:31:49 PM by eric48 »
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Offline Inchlingblue

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #31 on: August 02, 2010, 12:31:37 AM »
Eric, you're doing very well. On the one hand all of the calculations can maybe help you cope but make sure you don't overthink or obsess too much!

And if you cry when walking by the pharmacy make sure they are tears of joy for being fortunate enough to have access to good health care. ;)

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #32 on: August 08, 2010, 11:10:06 AM »
Thanks buddy!
****************
Your support helps in these difficult times (see below).
Let me add one side comment to one of your other posts: you said somewhere:
I work out pretty regularly but the other day I jogged for the first time in over 25 years! I'm 48 and did 1.66 miles.
My thigh muscles hurt the next day but in a good way and right after the jog I felt elated and invigorated. I'm pretty sure my cerebral blood flow must have improved.

Same here... I had let go of jogging but recently go back into it with one of the variants called slow jogging: it's jogging with very small steps. Someone walking fast would actually pass you.
Think of Mr Bean jogging and you have it. It was recommended to me as burning 60% more calories than walking, improving blood circulation as much as regular jog, but, avoiding the fatigue/stress on muscles that is in fact due to a raise in one acid in your blood (lactic? urea? I do not remember...)
It is worth a try, if you do not mind being ridiculed by kids...

http://video.google.com/videoplay?docid=4894531621070390634#

Just my 2 cents...

Side Effects
*************
I 'd wished I could say that every thing is OK.

But, unfortunately not the case ... On the Liver, everything seems OK, so far.

On Wednesday, from quite early in the morning to late in in the afternoon, I got this intense burning sensation on peripheral skin. Just like you have been sun burnt. Badly ...
There was no rash, skin (especially on legs) was a bit itchy, not even red, but that was not the problem: it was intensively HOT. Like a fever but not internal. Just on the surface.
(temperature, measured under the tongue was normal - I had some tachycardia, too)

That was not severe enough that I would rush to my doctor or the ER, but a bit more intense than just 'moderate'. Went away with the evening

The next day happened to be fever-like but less intense, and the day after was also hot, but again less.
Despite bearable, there is no way I could keep going to work under these conditions (actually on Wed. I had to skip work)

Saturday, I only had the 'usual' heat in the back of the neck and noticed, I was always feeling better (actually feeling fine) when in shops/malls or museum (because they have air conditioners) ,and it starts being 'bad' when I get out in the summer wether ...
At nights, I 'am fine... So  *** may be ***, it is a thermoregulation problem

It scared me because it was burning hot. I was expecting a rash to come out anytime, but it did not...
If it is a onetime thing, then lets forget it. If it ever comes back and again, it is going to be intolerable.
I am now well into the the 18 weeks surveillance time, so I just hope I can get by.

Today, Sunday, weather is cooler and me too !!! Today is a great day (at long last !). Maybe that is the trick (outside temperature)

I have gained some weight (2 pounds) despite working on it closely

Towards Once a day
***********************
Retrospectively, it way look strange that I was taking this combo in a 3 times a day (whereas it is a twice a day), but both Viramune AND Kivexa have liver/rash side effects so may be it was not such a bad idea (say, in the beginning)
I was worried that it was because I am now taking Viramiune and Kivexa both at 7:00PM (I also have one viramune at 7:00AM).
I decided that if that burning effect was back the next day, I would separate the timing a bit (as I was doing until last week Viramune at 7:00 and Kivexa at 10:00 PM)

Taking  Viramiune and Kivexa both at 7:00PM (at the same time) is a significant improvement on my daily routine. And of course, I am looking forward to the promising Extended-Release Formulation Of Nevirapine

http://www.medicalnewstoday.com/articles/195631.php
(Study Shows Once-Daily, Extended-Release Formulation Of Nevirapine Was Not Inferior To Twice-Daily VIRAMUNE In Treatment-Naive HIV-1 Patients)

If the extended release is approved, if I can stand the combo, and if it works on my virus, and if the HDL / LDL / Blood Sugar improvements are confirmed, then this combo is a winner (for me...)
Still a lot of ifs, but the more I advance, the better the outlook.

About Numbers
*****************

One of the specifics of this combo is that you get more blood tests than other people (to monitor liver parameters).
What I like in the article I quoted last week, is that regular blood tests could be used, to a certain extent, to prioritize the more expensive CD4 + VL tests in areas where these tests are challenging (cost, availability...)
In the same fashion, I am using MY numbers to validate a predictor or estimate for CD4 and CD%

The computation goes like this:
- take your latest known CD4%
- multiply to your current lymphocytes count to get a first estimate of CD4 count
- divide by your previous CD4 count
- apply this ratio to your CD4% to get your ESTIMATED  CD4%
- multiply this ESTIMATED  CD4% with your lymphocyte count to get your ESTIMATED  CD4 count

Since I coined this algorithm by my own, I am taking advantage of extra CD4 + VL test availability (at my OWN cost) to validate, at least on myself...
As of today, I only have 2 sets of data to play with and they are looking good. 

This simple algorithm, if valid, could be combined with the estimator that J. Hopkins researchers came up with and may help:
- those, like me, who have intermediate CBC and are anxious to know more about they immunologic/virologic response
- those who have to prioritize CD4% assay and VL assay in situations where it is not easily available

In this regimen, numbers play a more important role than in some others:
- they are thresholds in DHHS guidelines (VL must be less than 100.000 ; CD4 count less than 400 for males, 250 for females)
- Liver parameters must be monitored (ASAT, ALAT , CCT, etc.)
- Oesinophiles are something my doc was showing some concern about (I'll get back to it after I understand better), but that is yet another number to monitor
- HDL goes UP (which is a POSITIVE side effect)
- LDL goes up (while not so goodnews, the protective effect of HDL makes it acceptable): these are again more numbers to understand
- blood sugar/insulinoresistance (again more numbers) must be monitored for people at risk, like myself (in my case showing significant IMPROVMENT)

Hopefully next week will be better...

Cheers !

Eric


 
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Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #33 on: August 15, 2010, 04:55:58 PM »
Hi,

compared to last week this week was quite OK.

Physically, nothing to complain about and the week would have been perfect if I did not have this :

I had to visit a customer located quite far a way and had a lot of driving. It was hot and tiring. while driving I had this brain effect (which I have had before) that is a combination of brain-fog and contraction of the jaw.

It is not painfull per se by annoying. It usually goes away after 1-2 hours, but this time it lasted continuously for more that 48h. Because of the driving and customer call, I could not take the anxiolitic.

Contraction of the jaw during the night is a pain and I had to place some cloth in the mouth to get to sleep.

After I came back home the fog disappeared but not the contraction, which I again have even right now. I take the 1/4 of a pill anxiolitic (with much hesitation); helps a bit, but I do not dare take more because it makes me sleepy.

I have moved my Kivexa intake to the morning (I moved it forward 6 hours, then another 6 hours earlier the next day, therefore moving it from 7 PM to 7 AM)

The next 2 days, I had some kind of mild diarrhea twice (was a bit liquid and pressing). No big deal but if I ever have to do this again (time difference when travelling, etc.) , I should know and be prepared.

When the weather is cooler, I get better. I 'll make sure to get an air conditioner installed before next summer.

This jaw contraction may be due to taking Kivexa in the morning. I'll give it some time and we will see...

With this combo I have a choice of taking Kivexa in the morning or in the evening since I have to take Viramune twice. I , now, take my meds twice a day, which is a great improvement and I can go to a once-a-day, it will be even better !
(and I can then try placing it a the most appropriate time of the day, whereas, now, I still have to have a 12 hours difference between the 2)

Viramune (nevirapine) / Kivexa (ABC Abacavir + 3TC Lamivudine) and Diabetes
+++++++++++++++++++++++++++++++++++++++++++++++++++++++++

One of the things I liked about this combo is its good reputation with regards to diabetes. One of my concerns.

I quote here:
http://www.catie.ca/SideEffects_e.nsf/toc/A6A5AACCA7FAD09085256C7C006A51A2?OpenDocument

"there is some evidence that switching from a PI to either the non-nuke nevirapine (Viramune) or the nuke abacavir (Ziagen, ABC) may improve insulin sensitivity and lower glucose"

Before infection my blood sugar was borderline and I could feel the effects of this pre-diabetes state (tiredness after meals, strange feelings along the legs)
Fasting blood sugar was hovering between 1.0 and 1.5 which is (depending on doctors, the threshold for diabetes)
After infection, Blood sugar went up to 1.56 and remained there.
Right before meds, Glycosuria was 5.6 g/l (whereas there is none in healthy individuals) and Microalbuminuria was 45 mg/l (reference value : less than 20)
(in other words urine is brown-red)
Before starting the meds, Glycated Hemoglobin (aka A1C or HbA1c) was at 6.4, which is also above the defining limits of diabetes.
In general, the reference range (that found in healthy persons), is about 4%–5.9%.
The International Diabetes Federation and American College of Endocrinology recommend HbA1c values below 6.5%, while American Diabetes Association recommends that the HbA1c be below 7.0% for most patients
(http://en.wikipedia.org/wiki/Glycated_hemoglobin)

Blood sugar is raised by infections/inflammation, therefore, frank diabetes should be declared on non-inflammated state.
Therefore whether I was already in the Diabetes zone or not is debatable, but, honestly, was a real concern

A1C works as an estimate of average glucose over the previous 6 (?) months

The approximate mapping between HbA1c values and eAG (estimated average glucose) measurements is given by the following equation:

eAG(mg/dl or g/l) = 28.7 × A1C − 46.7

I should wait until my A1C stabilizes (which may take a total of 6 months) before I can use the above equation.
As of today, it would give:
May 2010 : A1C = 6.5  gives eAG = 1,36 (consistent with my Fasting Blood Sugar : 1.52)
end of June 2010  A1C = 5.8  gives eAG = 1,19 (consistent with a decrease of my FBS to : 0.93)
end of July 2010  A1C = 5.6  gives eAG = 1,14 (consistent with a decrease of my FBS to : 0.81 - my lowest ever, by far)

Recent research seems to say that measured data are biased by Abacavir (my case) and growing MCV  (also my case, see my previous posts)

I quote:

http://www.ncbi.nlm.nih.gov/pubmed/19502538

Relative to the control subjects, A1C underestimated glucose by 29 +/- 4 mg/dl in the HIV-infected subjects. Current nucleoside reverse transcriptase inhibitors (NRTIs), higher MCV and hemoglobin, and lower HIV RNA and haptoglobin were associated with greater A1C-glucose discordance. However, only MCV and current NTRI use, in particular abacavir, remained significant predictors in multivariate analyses. Fructosamine more closely reflected glycemia in the HIV-infected subjects. CONCLUSIONS: A1C underestimates glycemia in HIV-infected patients and is related to NRTI use. Use of abacavir and increased MCV were key correlates in multivariate analyses. Fructosamine may be more appropriate in this setting.

If data are biased by Abacavir, then previous indication that Abacavir is good for blood sugar may have to be revisited

Thus, my numbers *** may be *** biased and may warrant further analysis.

Nonetheless, I am quite certain that blood sugar has decreased significantly:
- my urine is (almost everytime) clear
- I do not feel the post prendial sleepiness
- Glycosuria is not to be found in my urine sample
- I just can feel it

I'll try this Fructosamine test, just to make sure how much my blood sugar has improved

If, as I think, it has improved this much that I am not in the diabetes zone any more, then it would be a MAJOR POSITIVE side effects of this medication on me. Then I will not have to take Metformin

Works for me, may be not on others.

Doctor was impressed by the change in blood sugar and A1C and asked me what is it I had done to get this (as if I was taking some medication or ancient recipe without telling him...)

Well no, doc, the only meds I've been taking are YOURS. Of course, I have being dieting (as usual, as my family is mostly obese, as I was) even more carefully and have lowered the carbo hydrates intake even more...
Some papers I had read seem to say that a proper low carb diet (and regular exercise) actually performs better than metformin

Possible causes for my blood sugar improvement since I started the meds:
- inflammation due to HIV has lowered
- this combo
- my diet (more carefull on carbs...) and exercise

I may never know which is which, but since diabetes is such an impairment of life (especially when getting older), I am quite hopefull that this will hold with time !

Since there is an overwhelming number of people using Atripla, I do not find much patient's comments with regards to this regimen and diabetes.

Have you seen your blood sugar IMPROVE or WORSEN ? I'd like to know !

This regimen is potentially risky and risks have to be carefully balanced with potential benefits. If there is a benefits there (for those concerned) , then it is worth it!

This Jaw contraction is still a bit worrying... Wait and see

Cheers!

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline J.R.E.

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #34 on: August 15, 2010, 08:09:23 PM »
Hi Eric,

I have a neighbor, that I haven't seen in probably 6 months. Because of my schedule we miss each other.  Well, I seen her last week.  This woman is about 60 years of age, and was always on the heavy side.

I couldn't believe it !! She had slimmed down, lost she said ( 65 pounds)  and she looks fantastic.  Looks like someone much younger, looked like a totally different person.

She was taking insulin,for diabetes,   but as a result, she no longer needs it, everything is naturally undercontrol.  She has changed her diet completely,  she's joined a gym, and goes three times a week,  and says she has never felt better!

Eric,  I think if you continue to watch you diet, get regular exercise, you'll continue to see improved results !!

As far as the Kivexa making the jaw contraction.  I never had this problem with Epzicom.

Yes, get that air conditioning !! It's been a long hot summer, and still got more to get through.This heat has been brutal for a lot of us.  I know I can't spend that much time out in it.

Good luck-Ray
Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #35 on: August 22, 2010, 05:00:19 PM »
Thanks Ray,

(Aug. 22) I am still having this jaw contraction thing and, honnest, it tires me. Other than that, everything is fine (still a bit constipated)

Yesterday, as I was preparing my pill box for the week, I just do not not why, some sort of reflex, I took the pill (Viramune).
I was preparing my pill box for the week and there it was in front of me, so, I (stupidly) swallowed the pill. 3 Hours ahead of schedule. No big deal.
During the night I had a bad episode of jaw cluntching. Bad. Cried a bit (something that has not happened for quite several weeks now). Because I am fed up with it.
I have tried several times the anxiolitic, but it puts me to sleep. So I did not use it (I had to make sure I wake up at 5 AM)

This morning, thus, I had to take my Viramune 2 hours ahead of schedule at 5 AM:00, and tonight, it is going to be 1 hour ahead and that is it...
Of course, I took my Kivexa on time at 7:00 AM. Thus there has been a 2 hours difference between my Viramune and my Kivexa. Just by chance, pretty much like I was doing in the beginning.

It seems to help a bit on the jaw thing... May be a timing issue. Maybe it is too early for me to take Viramune at the same time as Kivexa.
Otherwise taking Kivexa in the morning (and along my viramune) did not seem to produce any problem, and it was very handy...
Maybe... When I had mentioned to my doctor that I was taking Viramune at a different time than Kivexa, he shrugged, as if it was pointless. Maybe not so. May be it was a good idea after all (at least at initiation)

I can live with the idea that I should give it time...

It is just unexpected...

Tomorrow I have some blood work... Will know more soon and I 'll be visiting my doc on Thursday.

Thanks for your kind support. Stay tuned

Cheers!

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Good Labs Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #36 on: August 24, 2010, 05:49:35 PM »
Got my lab results same day as blood work...
Everything in the GREEN. All hopes and expectations CONFIRMED !

CD4 : 780 CD4% 30 % VL : 220 (so check point at month 3 is PASSED !)
Blood Sugar (diabetes concern) : very good
Cholesterol : SUPER !
Liver and others : Nominal

Some data still missing . Will post full details Sunday when I have them in front of me and after Doc visit.

Doc visit is going to be quite cool (I expect...)

Stay tuned

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline J.R.E.

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Re: Good Labs Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #37 on: August 24, 2010, 09:01:35 PM »
Got my lab results same day as blood work...
Everything in the GREEN. All hopes and expectations CONFIRMED !

CD4 : 780 CD4% 30 % VL : 220 (so check point at month 3 is PASSED !)
Blood Sugar (diabetes concern) : very good
Cholesterol : SUPER !
Liver and others : Nominal

Some data still missing . Will post full details Sunday when I have them in front of me and after Doc visit.

Doc visit is going to be quite cool (I expect...)

Stay tuned

Eric


Looking good Eric !!!!  Numbers are great ! 


Ray 8)
Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline eric48

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Virologic failure ? Already ??? Kivexa (Epzicom) + Viramune
« Reply #38 on: August 29, 2010, 05:54:10 PM »

Virologic failure ? Already ? Kivexa (Epzicom) + Viramune

Doc says my jaw tension issue is PTSD (stress). I said I do feel much better about the whole thing now and that I have no reason for anxiety (I have even dropped the anxiolitic).(BTW, I am back to taking Kivexa at same time as Viramune)

He insisted, saying that I have been through a lot recently...
He was smiling (out of sympathy, he is such a nice guy, truly is, charming eyes, too...)
I WAS NOT (I am fed up, included with myself...)

And ... I was happy with the lab results.
Here they are: at 11 weeks
HIV: CD4 782  ; CD4% 30 ; VL 220
CD8 % : 48  CD4/C8 ratio 0.63

Baseline was:
CD4: 440 CD4%: 18 CD8%: 61 VL: 65k (4.82 log)
CD4/C8 ratio 0.25


Liver: Unchanged
eosinophiles : now down to 3 % (max 5.5 - baseline 2-3 %)
(eosinophilia is a listed side effect of Viramune but remained within range)

Diabetes: Fasting Blood sugar: 0.86 (BL: 1.56 during infection; 1.05 before)
A1C : 5.4 (BL: 6.4) (all within range; Doctor still suspects I really must have done something I am not saying)

Cholesterol : HDL : 0.66 g/L (great !) (BL : 0.35)
LDL : 1.20 (down from last month 1.57 BL: ca. 1.10-1.20)
HDL/LDL ratio: 0.55 (which is super good and best ever) 

Our local guidelines for virologic success requires
more than 2 log VL decrease and/or less than 400 at 3 months (i.e. 13 weeks)
decrease is : 4.82 - 2.35 = 2.47 log. and VL is 220. So everything is fine is it not ?

Blood work was done 2 weeks ahead of schedule (Doc visits are out of pace because liver monitoring is at 2 weeks, then monthly- this is why it was done at 11 weeks)

If this jaw tension (I have less of it now, but still there) is due to stress, then the cause might be my concerns about VL (went down very fast, then kind of slowed down)

I did not want to ruin the day and did not mentioned that I had some concerns about this VL

Doc said that CD4 where much better than one could hope for (and some how wondered why)
He seemed happy

I did not want point out the VL.

HE DID !!!

Doc : one thing worries me, though...
Me : has to be VL,then
Doc : Right. That stands out
Me (to myself) : shit, I knew it...

Doc expresses concerns, hesitates a while because blood drawn a bit early, mentions that Nevirapine (Viramune)
has a low barrier to mutation, calls the biologist over the phone and orders an extra drug resistance test (genotype) on last month results
(where VL was 700, therefore, still high enough, this time blood sample is at VL 220, too low for genotype)

Oh Boy, this infection is a journey of sorts !

Doc wants to cool me down and says we have solutions in case...

And here he is, discussing about a possible switch to PI (potent, once-daily, but not so lipid friendly) or Isentress (lipid friendly but twice a day)

Holy shit !!! (excuse my French...). I came in, trying to focus on the beauty of the results, in order to reduce my stress

And here where are: he is laying ground work for resistance and switch talk.

Strangely enough, it does not ADD stress but rather reduces it since I know he is taking a very cautious step (genotyping)

I just knew it. I (kind of) knew my body would respond well, but virus be a bit more tricky (one mutation already registered)

Next visit in 3 weeks (well enough to get that resistance test done, he said)

I promised myself to go to the lab at month 3 sharp (09/09) and get a CD4+VL and bug the biologist about the genotype.

I sure want to have time to review my options before the next visit...

I left , a bit disgrunted ... then rushed into the local bath house for a cheering up (protected) fun, that was actually quite enjoyable.

One Roller coaster day ...

Eric








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Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #39 on: September 05, 2010, 07:24:21 PM »
ept 5 2010

Nothing new. Jaw crunching still around; may be a bit less noticeable. Doctors say this is stress... Well this has been lasting since Aug. 12 (now 3 weeks!)
It better stops or I'll start questioning all these meds flowing through my brains.

Fructosamine results came back at 250. This is within range. I'll use this to evaluate whether the above mentioned report stating that Use of abacavir and increased MCV may lead to underestimation of glucose level if using glycated hemoglobin


www.viramune.com has a good monograph
http://www.viramune.com/downloads/Vir_mono_apr06.pdf

It states:
Unless the clinical benefit outweighs the risk, VIRAMUNE therapy is not
recommended for women with CD4 cell counts >250 cells/mm3 or men
with CD4 cell counts >400 cells/mm3.

because my CD4 cell counts >440 cells/mm3. (I had 3 readings: 440,535,450), I sure want to see the 'clinical benefits'

Generally speaking, Viramune is said to be beneficial for HDL (same is said for Abacavir) while only slightly increasing LDL
In my case, and as of today, this is confirmed

Same with Abacavir, I sure want to confirm the benefit outweighs the risk.
Abacavir is said to be good for people with diabetes concerns.
In my case, and as of today, this is confirmed

But, that holds true ONLY IF the medication is not biasing the lab results !  (cholesterol/blood sugar)

Seen from my doctors perspective the advantages are:
- more penetration into CNS (reduces VL in the brains)
- reduced VL in semen

OK Doc ... But considering that I do not interact with others that much and if so I ALWAYS use condoms ( a 25 years - 100 % adherence to this policy that had one and only one YET DRAMATIC exception - I've learned my lesson !)

I didn't know that the tissues at my bedside were at risk of infection !!!

So now my brains are fully loaded with ARVs: they'd better be protective !!
And I hope that they are not the cause for that tension I keep having on the Jaw

Seen from my perspective the advantages are :
- good for cholesterol
- good for blood sugar
- once-daily down the road
- saves Isentress and PIs for future use (in case of resistance)
- less CNS risk (read all those threads about Atripla...)(1 % vs 11 % for Efavirenz)

So far so good.

We are still waiting for the genotype (possible resistance)

BTW, the CD4 cell counts >400 cells/mm3 comes from the 2NN study. Since the >400 cells/mm3 has been established, less AEs had been seen in other studies, too.
YET, reports from doctors in ressource limited settings where Viramune (nevirapine) is used regardless of this recommendation seem to contradict this increased liver toxicity risk.
(eventhough, I doubt that in these settings they initiate often at above 400...)

If it were not for the above, I would have preferred I&T
I now think he did not offer that because I&T is not yet in the recommended list for treatment naives here (it is in the US...)

Also, we now know more about Isentress...

http://www.thefreelibrary.com/Prezista+and+Isentress+can+get+into+nervous+system+and+brain+to...-a0219589806
Prezista and Isentress can get into nervous system and brain to attack HIV

If the resistance (genotype) comes back with bad news, then I&K is a good candidate, I guess ...

Cheers!  Eric
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Offline eric48

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Resistance to Viramune + Kivexa (Epzicom) Already ???
« Reply #40 on: September 11, 2010, 04:20:17 PM »
Resistance to Viramune + Kivexa (Epzicom)

Hi,

I do not know how to put it. Let's be factual
I went to the lab to inquire if the genotype that my Doctor ordered was done. I said I need the information because I need to schedule an appointment.
They confirmed that the results had just been sent to him that very day. They would not give the results to me. I did not make an issue of that I was way too much under stress.

I got my blood drawn to get CD4 count and VL right at month 3 (started meds on June 9, blood work was on Sept 9)
Got the results yesterday.

I hypothesized that if the CD4 count was stable more or less and VL going down then, I could be hopefull that the resistance test would come up clean.

Unfortunately, CD4 count is down to 550 (from a low 800 2 weeks before) and % is also a bit down (28 % down from 30 %) and VL slightly up 242 (vs 220 , 2 weeks ago)

The CD4 count drop is not small... I hope the resistance test shows something (even if it is bad news), because if it does not, then, well ... I do not know...

Doc has a lot of experience, so ... And I would not mind a switch. I think I 'd prefer a switch to a combo that it working poorly.

I do know I do not have much to fear and so on. For the last few weeks I have had good nights and no crying, no fainting , no nothing (but for a tension in the jaw that is slowly fading)

Today, I even had a tiny bit of discomfort in the liver area, which made me notice that have not had that for days...

While waiting for the lab there was that great looking guy who came in, he was JUST my type (and my taste is not one of the easiest), RIGHT ON; but I do not like to dream about the unreachable, I could not help my self, I guessed. He was on his way back. Had a eye contact first , then a second.

I was so depressed, I did not run after him. I regret that now. He's been on my mind since. 

I stand on a razor edge between the prospects of success and that of failure.

Crying is back.

Appointment with Doc is on Monday, first thing.

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #41 on: September 19, 2010, 06:21:46 PM »
Resistance or not ?

Doc: I have one good news and one not so good
Me : shoot
Doc: the good news is that the genotype does not show any new resistance (as of end of July), bad news is that VL is somewhat high (242)
Me: ...
Doc: that is still within target, though, we 'll just monitor it a bit more closely, next CD4+VL in 6 weeks...

Side effects?: I still have this tension in the jaw muscle, may be a (tiny) bit less, a bit less constipated too, some times a bit itchy... Nothing else
well, I do have something else: skin on the legs gets some tiny muscle contractions...repeateadly, erraticaly, like some allien is leaving underneath.
He gave the name for it... said is has no clinical significance
Me : ...
Doc: your side effects are an intellectual challenge to me (he smiles)
Me (by myself): Well, doc, I am not here for your intellectual enjoyment !!!

I hope this regimen will work for me: it has proven good for me (blood sugar and colesterol profiles have improved and I do feel it)
and can be once a day down the road...

If I need a switch he said Isentress is a good candidate eventhough it is twice a day. Same feeling here.

Discussed popularity of regimens, which, based on this forum, this Nevirapine + abacavir + 3TC is not the most common.

Doc: yes, I must admit. I only have 2 or 3 patients on that. And they are inherited patients (they came too him after starting treatment)(note: he has got a lot of patients and experience, I have checked that...)

WhAAAAAT ?????? I am the first patient you are initiating on this regimen ?????

(No doubt, I feel nervous... I kind of knew it... Is he experimenting on me !!!???)

Discussed new meds/options, etc.

He then made a point, which, in my humble opinion makes a lot of sense about my combo (Viramune + Kivexa), which is not so common. This combo carries a long list of POTENTIAL side effects, it scared the S*t out of me...

The list itself is long, but, me, knocking wood, I am so far doing fine... A long list of possible side effects does not mean a high probability of getting SE. They are just very diverse. Atripla has a much shorter list, but as many as 20% seem to complain about the CNS SE.

The longer list may be one of the reasons why Viramune appears to be less popular amoung the people in this forum.

Another example: read the list of potential side effects ABACAVIR (which I am taking) is carrying. Sounds like a complete series of Dr HOUSE , MD, they are so many and so scary. They are not to be taken lightly.

Yet, in one study (don't remember which) over 500 naives initiated to ABACAVIR , only 4 got these SE (and in fact 2 of the patients, if I remember well had other conditions HVC, what have you,  do not remember). This is LESS than 1% !!!

Doc said that some of his colleagues are teasing him for still prescribing Viramune

Sometimes a small study involving a mere hundred patients shows good results and, all of the sudden, this med becomes instantly popular (see QUAD), at the expense of the 'older' ones.

He said that MILLIONS of people are (or have) taking Viramune, daily, for years (it has saved millions of lives). If it were THAT bad it would show!

I thought that comment made a LOT of SENSE. A hell lot of sense...

I love the guy ... He is HUUUGE, I feel sorry for him when I see his HUUUGE fingers stricking his keyboard, He should ask Hagrid for a giant Wizard version.
I can't even say how big he is, he's beyong my usual scale. He's got that deep, profound voice, that connects to people. Charming eyes too.

He taps my belly (liver exam...)
Doc: hear it, you're full of air
Me : not air, doc, gas... I'm constipated, I'm full of S**t
Doc: that's what I meant... LOL (he, literally, speaking went LOL !)

Doc: And also, you have Respiratory sinus arrhythmia (RSA)
Me : .... (what the hell is that new thing ??)
Doc: your heart speeds up when you breath in and slows down when you breath out
Me : ??? !!! ???
Doc: It is usually found in adolescents or people with great control of stress (Me ??? no kidding !!!)
Me : well, there is still a lot of a teenager left in me (I was trying to be funny, - failed - but, this is quite true, in fact...)
Doc: ...


(wikipedia says: The term sinus arrhythmia refers to a normal phenomenon of mild acceleration and slowing of the heart rate that occurs with breathing in and out. It is usually quite pronounced in children, and steadily decreases with age. This can also be present during meditation breathing exercises that involve deep inhaling and breath holding patterns.
wikipedia adds: Adults in excellent cardiovascular health, such as endurance runners (my case?), swimmers, and bicyclists, are also likely to have a pronounced RSA.

So, this is pretty good news: Heart is in good shape... Come on sweety boys, this old fellow still young and H...y !

I started this thread because I could not find much on the Internet about this combo. I was kind of worried.

I am NOT worried any more... The slow virologic reponse was kind of anticipated (being older, etc...).

I'll carry on for the excitment of the (not so few) readers

also, did not cry during the interview (for the first time) : some progress on this front too...

Resistance or not ? : we still linger in the lymbs of the unknown... And it is quite enjoyable !

Cheers Eric


  
« Last Edit: September 19, 2010, 06:24:35 PM by eric48 »
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Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #42 on: September 26, 2010, 05:14:29 PM »
Just came back from a week in Africa. Didn't get any additional health issue. The tension on the jaw is still there... May be a little less today. If this would go, life would be a breeze.
Cheers Eric
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Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #43 on: October 04, 2010, 08:28:22 PM »

That chronic tension on the jaw (and sometimes brain fog) is a pain in the butt (well, no... in the jaw, but still...) Therefore, I have moved my Kivexa time upwards to PM intake. At first it seemed beneficial, but, now, I   am not so sure. maybe slightly better. This problem arised 2 weeks after changing timing so I will give it some time and see if the timing change resolves it.

if THAT wasn't there (and such a low noise impairment is a real annoyance) I would dare say that my general sense of well being (say energy, strength, interest in things, etc...) is actually BETTER than before infection (sic...). Meds have improved my HDL and insulin/sugar resistance that are insidious age/aging effects.

I have much longer, efficient working days, much less naps (if ever) (and if so shorter); it is like the clock is ticking backwards. too bad this med-induced-stress-mimicking-effect is ruining the day(s)...Wait and see...

one funny thing, the other day, I was doing some internet search on Viramune (nevirapine) and ended up reading my own thread. I also found interesting things...

this one for example:

------------
http://www.ncbi.nlm.nih.gov/pubmed/20679961

Development of new HLA-B*3505 genotyping method using Invader assay.

Hosono N, & al

Several pharmacogenetic studies have revealed strong associations between specific human leukocyte antigen (HLA) alleles and the susceptibility to drug hypersensitivity. Recently, we reported HLA-B*3505 as a strong genetic biomarker for the nevirapine-induced skin rash in Thai population. Here, we developed a new HLA-B*3505 genotyping method by a combination of the Universal Invader assay and sequence-specific primer PCR. From the sequence alignment of 68 HLA-B alleles in the Thai population, we selected the two most discriminative SNPs (rs1140412 and rs4997052) as target SNP sites. When we carried out the assay using 324 Thai individuals, fluorescence intensities of HLA-B*3505-positive and HLA-B*3505-negative samples were apparently discriminated at the endpoint of the reaction. Our results were 100% concordant with those obtained by a sequence-based typing method. As our assay is simple and rapid, we believe our method will be a useful tool for pharmacogenetic testing of the nevirapine-induced skin rash.

------------

If I understand well, and if it works like the HLA B*5701 genotype screening now enforced for Abacavir, it would at the same time reduce the number of people iniated to Nevirapine (in the same fashion that less people are iniated to Kivexa than to its virologically quite similar Truvada), it would also reduce the incidence of skin rash SE, which from the user perspective, is good news !


This one is interesting too...

-----------

http://www.ncbi.nlm.nih.gov/pubmed/20668070

J Virol. 2010 Oct;84(19):10230-40. Epub 2010 Jul 28.
Estimating frequencies of minority nevirapine-resistant strains in chronically HIV-1-infected individuals naive to nevirapine by using stochastic simulations and a mathematical model.

Gadhamsetty S, Dixit NM.

Nevirapine forms the mainstay of our efforts to curtail the pediatric AIDS epidemic through prevention of mother-to-child transmission of HIV-1. A key limitation, however, is the rapid selection of HIV-1 strains resistant to nevirapine following the administration of a single dose. This rapid selection of resistance suggests that nevirapine-resistant strains preexist in HIV-1 patients and may adversely affect outcomes of treatment. The frequencies of nevirapine-resistant strains in vivo, however, remain poorly estimated, possibly because they exist as a minority below current assay detection limits. Here, we employ stochastic simulations and a mathematical model to estimate the frequencies of strains carrying different combinations of the common nevirapine resistance mutations K103N, V106A, Y181C, Y188C, and G190A in chronically infected HIV-1 patients naïve to nevirapine. We estimate the relative fitness of mutant strains from an independent analysis of previous competitive growth assays. We predict that single mutants are likely to preexist in patients at frequencies ( approximately 0.01% to 0.001%) near or below current assay detection limits (>0.01%), emphasizing the need for more-sensitive assays. The existence of double mutants is subject to large stochastic variations. Triple and higher mutants are predicted not to exist. Our estimates are robust to variations in the recombination rate, cellular superinfection frequency, and the effective population size. Thus, with 10(7) to 10(8) infected cells in HIV-1 patients, even when undetected, nevirapine-resistant genomes may exist in substantial numbers and compromise efforts to prevent mother-to-child transmission of HIV-1, accelerate the failure of subsequent antiretroviral treatments, and facilitate the transmission of drug resistance.

------------

The take-home message for me is not clear, but if I understand well, if a (drug resistant) mutant appears, it is because it pre-exists, and if so at a level fairly high, but not so high that it can be detected at pre-initiation genotype (where VL is 4-5 logs), but still fairly high and thus it should not be missed at a post-initiation genotype (mine was made at 600)
and since no resistance was seen, then it makes me hopefull that there is no resistance

I still keep my fingers crossed, though...

Cheers

Eric   
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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #44 on: October 17, 2010, 06:24:52 PM »
hi,

Since I am taking Abacavir I am interested in knowing more about it. There is a controversy about the potential higher risk of heart attack. Not every report is consistent...

This interesting post :

http://forums.poz.com/index.php?topic=34685.0

points at:
http://www.aidsmap.com/page/1518618/

and subsequently at:
http://www.cphiv.dk/TOOLS/NNHforabacavir/tabid/436/Default.aspx

I have played with my numbers...

if I take my pretreatment numbers (non smoker, systolic 120, total cholesterol : 160 mg/dl HDL: 35 age : 48) and on borderline if diabetes (means I calculate with and without ...)

if I choose diabetes : no : NNH for abacavir and given patient profile is 141 (Framingham 5-years risk while on abacavir is 1,5%)
if I choose diabetes : yes : NNH for abacavir and given patient profile is 62 (Framingham 5-years risk while on abacavir is 3.5% !

So my doc should certainly consider avoid ABC, but since he did not (obviously), I should certainly get nervous (which I did, obviously...)

BUT, if I take my latest numbers (under this combo : viramune + Kivexa (Epzicom), and since my lipid/sugar number have drastically IMPROVED (thanks to this combo, there is no other reason...)
namely:
(non smoker, systolic 110, total cholesterol : 199 mg/dl HDL: 66 age : 48) and clearly diabetes :no

then NNH is 766 (Framingham 5-years risk  while on abacavir is 0.3%)

more interesting if I take my preinfection numbers (non smoker, systolic 120, total cholesterol : 172 mg/dl HDL: 38 age : 47) : the underlying Framingham 5-years risk for the specified patient profile is 0.6%

The funny outcome of these calculation is that my Framingham 5-years risk is now LOWER than before infection! (even with Abacavir)

Somehow, this is a bit ridiculous and a bit unfair to the nice research work that is reported here.

Those calculations are highly relevant and helpfull when it comes to making decisions and your profile already sets you in the at-risk pool.

As for myself, I am in the low risk end and those number kind of loose relevance.

I did it just for fun ...

Speaking of the choice of treatment (amoung options left open after genotype...):

http://www.iasusa.org/pub/topics/2010/issue3/112.pdf

is a nice, free wrap-up article

With regards to my Side effects aspects the only thing left is this tension on the jaw that diminishes only very slowly

I have done some research on resistance and viramune with regards to resistance: I am not too worried... Labs are next week...

Wait and see...

Cheers

Eric



« Last Edit: October 17, 2010, 06:28:18 PM by eric48 »
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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #45 on: October 23, 2010, 06:52:31 PM »
Labs as of Oct 21:

CD4: 621
CD4% : 32
CD8% : 44
CD4/CD8 : 0,73

HDL: 77
LDL:  138
A1C : 5.1 %
Liver panel: right on

tension on the jaw : a bit less every week. Still there, hardly noticeable.

I am still not UD ... (VL at 217 (log 2,34 at week 19 ...) and THAT is depressing...

Meeting with doc next week... We will see...

Cheers! Eric
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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #46 on: October 24, 2010, 06:39:10 PM »
In a rare twist of history one of my family members invited me to an open doors at our local NIH equivalent as part of a fund raiser. (that side of our family runs a foundation that donates a lot to cancer research)
visitors were randomly directed to various labs and the lab tech/manager gave presentation about what they do.

The most unexpected thing of all is that, by the most unexpected chance, I was assigned to visit the very lab and receive explanations from the very same person that has signed off my genotype tests!...

That was emotionally hot. (one girl actually fainted during one of the conferences...). I, myself, was very unprepared too...

I've just got to see with my own eyes the very people who are doing this research here, in their working environment.

Actually a genotype test seems to be very labor intensive... And the equipment they use seems so basic (and ancient...) so much different than the luxury labs of big pharma.

there was a hands on on gel electrophoresis as part of the open doors (on a colorant not a real sample) and I volunteered.

That was so unexpected ! (and cool!)  Eric
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Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #47 on: November 28, 2010, 06:12:44 PM »
Doc Visit (Oct 26)

I am still not UD ... (VL at 217 (log 2,34 at week 19 ...). Let's see what doc has to say:

I am usually looking forward to visits to my doc. Its some privileged moment, personal... I admire the guy, he is also so much the opposite of me

The mood was not to good. There was a bit of a commotion in the waiting room with one patient sharing (loudly) his personal experience with rash, lack of adherence, sickness, etc.
I was not in mood to hear that...

Doc: got your VL results. Could not sleep half of the night because of that
Me: we're even, I could not sleep the other half
Doc: I have not told you which half I could not sleep
Me (trying to save the day) : don't bother, I could not sleep neither halves
Doc: ...
Me : ...

Doc: checkpoint is VL < 50 at 6 months. Your VL is somewhat high that is what worries me.
Me : ...
Doc: we are not yet at Month 6, so let's carry on, we are not yet out of the set guidelines
Me: I agree
Doc: next blood draw Dec. 6. VL below 50. That's our red line. Not negotiable. Resistance is too serious an issue.
Me : I know

His eyes are daring me. I do not care, I do not look at him in the eyes. I can only look at his huge fingers on his keyboard
That is because I know we are not going to be below 50 on DEC. 6.

I also know why, but I am not saying anything.

I pretty much liked the fact that he could not sleep because of me. Liked to share the pain, the distress, the crying at nights, the praying (is there a prayer against resistance?).

Me : do not worry, I am comfortable with whatever comes up...

Yes, let's see what you've got under the hood when you will have to declare me a 'virologic failure'

Next visit will be a tough one. I do not mind a man-to-man, Will see if you duck in or got some balls ... Herr DoKtor !

And, at long last, I am starting to find this interesting and exiting!

looking forward to the endpoint !

Fist up.

Eric
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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #48 on: November 29, 2010, 01:32:28 AM »
Eric I would think if you were actually having treatment failure your VL would be a lot higher than 217.

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #49 on: November 29, 2010, 10:22:36 AM »
Eric, you had a genotype test that only revealed the T215E mutation which only rules out AZT and d4T. So, unless you've not been adherent, I wouldn't think resistance was your issue. Your VL is practically UD now. On tests that were still in use only a few years ago, you WOULD be UD NOW. Try to not sweat it so much. Chances are very good that you'll be UD very soon.
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"...health will finally be seen not as a blessing to be wished for, but as a human right to be fought for." Kofi Annan

Nymphomaniac: a woman as obsessed with sex as an average man. Mignon McLaughlin

HIV is certainly character-building. It's made me see all of the shallow things we cling to, like ego and vanity. Of course, I'd rather have a few more T-cells and a little less character. Randy Shilts

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #50 on: November 29, 2010, 03:08:46 PM »
Hi Guys,

Thanks. In the bottom of my heart and from learning so much in this forum about individual experience, I believe you are right.

Nonetheless, in our socialized health care system, HIV clinics, allowing doc to appreciate case by case, is all new. The one I am going to is the first one and has opened only very recently. My long timer Doc had to leave his hospital practice (and monthly salary) to go private and I believe that they have established sets of rules where patients have to be handed back to hospitals. Reaching 50 at month 6 is one of these rules (as I read them...). They are keeping a leash on him... Now, what kind of attitude my Doc will have, I still do not know.

Believe it or not I may very well have been the very first newly infected patient there. (other patients are mostly follow ups, I assumed). The paint was still wet when I walked in...

My doc said he could not sleep half of the night because of my case. I therefore assume he could have a good, sound, sleep the other half, then... The reason why my VL decreases only slowly is something I hope to investigate a bit further. This way, I can share my personal experience with confidence and support others in the same situation.

Intellectually speaking, I am not worried. Strangely enough , since my POZ test, seems like my intellectual self and emotional self have dissociated themselves...

Thanks again for the support

Eric

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Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #51 on: December 06, 2010, 07:06:57 PM »
Blood test today, results received late at night...

BINGO !!!

Stay tuned

A very happy Eric
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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #52 on: December 12, 2010, 10:01:32 AM »
Blood test today, results received late at night...

BINGO !!!

Stay tuned

A very happy Eric

So tell us what's going on Eric!

Ray
Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #53 on: December 12, 2010, 06:44:32 PM »
Hi Ray,

Recently I have been reporting a bit less in this thread because I have been distracted by other issues and do need to move on or at least be less obsessive in order to ease my stress issue (the tension on the jaw, which is still there but fading)

Yet, eventhough it is past midnight, I'll be happy to answer you: you help in this matter has proved priceless

A moment of truth
*****************

I have kept reporting on this (monologous) thread because I have realized a good number of people are reading it.

I had initiated it because this combo is less used and it is hard to find patient's experience on this, but I know for a fact that lots of people do read this forum, looking for information, even if they are not participating themselves.

I have been a bit cautious recently in reporting real time because I, sometimes, needs a bit of time to analyse things before stamping something that will stay in this thread forever.

sometimes I can get so self-convinced that I can be led into entering controversy and the last thing that this thread needs is controversy.

My gut feeling is that this combo works very fine for me. After all the anxiety of the initiation, the last remaining issue is virological success (or failure): it is also the most important

It would do a disservice this combo and the readers who are considering it to report alarming labs.

My VL is going down slow... That is a given fact.

So what ? It's MY body, MY virus and MY combo.

Here, in this country, if your VL is above 50 at month 6, you are declared a virological failure, and, I, personally hate failures (in general).

All markers were pointing to a slow but steady decrease, yet, my projection was that I would be a bit a above the 50 landmark.

What if it is 70 ? or 60 ?

Preparing for a doc visit under these conditions was psychologically and intellectually exhausting.

As we got the results, the discussion with my doc could have lasted no more than 5 minutes.
It lasted 1h and 1/2 (as usual...), because I wanted to get to the bottom of a few issues, and, that, I'll report later.

let me give you the results raw and I'll comment next week.

HDL : 0.78 ( cool !!!)
LDL : 1,38 ( fine with me...)
Fasting sugar : 1.01
A1C Hemoglobin : 5.2 % (a dream come true...)
Everything else (liver, kidney, etc.: perfect)

CD4 : 707
CD4% : 32 %
CD4/CD8 ratio : 0.78

and last but not least:

VL : 48 ! ! ! ! ! ! ! !

That's all folks ...

Cheers and thanks for you continuous support

Eric

NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline J.R.E.

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #54 on: December 12, 2010, 08:51:51 PM »


HDL : 0.78 ( cool !!!)
LDL : 1,38 ( fine with me...)
Fasting sugar : 1.01
A1C Hemoglobin : 5.2 % (a dream come true...)
Everything else (liver, kidney, etc.: perfect)

CD4 : 707
CD4% : 32 %
CD4/CD8 ratio : 0.78

and last but not least:

VL : 48 ! ! ! ! ! ! ! !

That's all folks ...

Cheers and thanks for you continuous support

Eric



That's fantastic news Eric!! Congratulations !! Thanks for checking back. Keep in touch when you can,  I am always checking out this thread.


Ray 8)
Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #55 on: December 20, 2010, 05:28:07 PM »
Hi,

Back to reporting... Doc had scheduled a 1 hour slot. discussion lasted much longer... Many issues have been discussed.

I'll report those which are of interest to this thread, mainly aiming at providing information about this once demoted regimen.

I am trying to guess who reads this thread as so few of us are reporting being using this combo ...

- search engines and crawlers
- regulars (thanks again Ray !)
- those who are anxious as their doc recommended this somewhat out_of_fashion combo whereas there are many other cool alternatives (and they wonder why...)
- those who are anxious as their doc prescribed this because of LIMITED choice in their country (and they feel frustrated...)

Access to information (Internet) is far less expensive than access to the meds themselves. Sometimes I feel for those, born in a poorer country, as they read on the Internet all those cool news about meds they will never be able to afford.

This report is for them. Me? as far as I am concerned, HIV is : PROBLEM SOLVED (so far...). I hope to help others

Before I start let me say this: me being slow in VL decrease is NOT a meds issue. It relates to my personal, individual dynamics.
So if the previous reports had been a bit alarming about resistance, stay reassured, I am strongly convinced this combo works for me (but I'll keep checking)
I have taken a number of blood test in between which I have not reported as they are being collected for an other purpose.

Doc: Well this number (48) is better than you had projected.
Me: Yes, on one hand it is a relief. on the on other it deprives me from the right of a virile discussion with you about the choice you had made (meaning : we are going to have this discussion no matter what)
Doc: Before we start, I see no reason to switch you from a combo that you seem so found of. And also, the alternative that we had considered (Isentress and Kivexa) will NOT be a once-a-day with me.
Me: I know that already... Do you know what I like most about this combo ?
Doc: ??
Me: It is LOW COST
Doc (surprised): indeed one of the least expensive. But does that matter to you ?

(side note: the monthly cost of the med is what I charge my clients for one HOUR of my time... not that I am bragging about that, but it helps explain my docs comment)
(my doc is a Humanitarian type, doctors-without-(sex)-borders type, I'm a hardcore selfminded entrepreneur, sort of)

Me: if all the money I have spent in (uncovered) tests and monitoring can help people who can not afford that luxury, then it is money well spent
Doc : (smiling)
Me: Low cost, high risk, high return. I love that !... You had become a bit nervous, no ?
Doc: well...
Me : now, if you would even start to think that I might fear that the meds are only working halfway, then you'd be mistaken.
the meds work or they don't. For me, (thus far) : they WORK
Doc : I am happy to hear you are so positive

(being 'so positive' in the mouth of an HIV specialist is somewhat, hum... bad taste... But, hey, we are having a frank discussion, here)
Me : I'm sure you would want to know why (now, he is cornered...)
Doc: Sure, I do (do you really ?)

Do you want to know why I think it works (very) well for me ?

Do you ?

Then stay tuned... and see you next week

Happy Holidays everyone !

Eric



 
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #56 on: December 31, 2010, 06:11:11 PM »
On one hand I am happy that I have a doctor that is so involved and offers a reassuring, comforting approach.
They even offer a trained psychologist and assistants for discussion, etc. (I declined, though)

It is important to have someone to talk to.

On the other, I can not help it. The wait to UD, the fear for SE, the sense of urgency on every thing (clean up my financials, work, ..., just in case...) as opposed to the long wait for something that might not even come (toilets, UD, failures of all kind)
has drained a lot of my energy.

I talk to my doc every day...

Even have his picture on my PC, by my bedside.

I MUST understand, sort, clarify, classify, no stone left unturned.

I have a one time chance to talk to him for real. I realize that this is a rare chance I have that he spends some time with me (and most likely many others, too...).
It is a privilege that not everyone can enjoy (socialized health care or not)

But drawing ones doc attention is something than can be earned:

- educate yourself (so that he does not get bored with answering trivial questions)
- prepare your visit
- list items on your current health (side effects, weight gain or loss, mood, etc.)
- list your questions (in writing, you should leave the interview with an answer for each of your questions)

Somehow, try to make the interview entertaining for him/her as well !

Before I tell him what I think of the whole thing, I had to put things straight with my doc:
- that I did my homework the best I could, but so many concepts are so new to me
- That I think he was quite alarmed at month 4 (and so was I)
- that we need to analyze it, understand it before we put it behind us and move on

That being said, the discussion could begin...

There is untimely interruption in this report, though...

We are 3 minutes to midnight and hence, to 2011. It is New Year's eve !

I have 3 minutes left for a thank you note:

- the people I have met through this journey (docs, nurses, biologists...) they know and have been very comprehensive
- the people who around me and do not know (family, coworkers, etc.) : their just being around has been helpful in many ways !
- the people on this forum :it is a truly open and challenging place

And at this very minute it is New Year !

Family is asleep, but I'll sneak out with a bottle(s) of champagne and plastic glasses and share it with the crowd that has assembled in front of the City Hall and is celebrating

Happy New Year everyone!

Eric  




« Last Edit: January 02, 2011, 02:11:08 AM by eric48 »
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #57 on: February 15, 2011, 06:30:16 PM »
Feb 14

Hi,

The reader deserves that I carry on my report on discussion with my Doc about the time it took me to become UD.
Simply because some reader may be offered this combo as a choice and this thread is about collecting pros and cons as well as patient's experience.
What makes it difficult to report is that once you state something, in an informative thread like this one, you do not want to be dragged down into fruitless controversy.

Therefore, before exposing the discussion with my doc, let me get back to one thing.
Sometimes, I have said things as if there were obvious, because I got them from him and I take it it is common or current knowledge.
This is not exactly what I have experienced in posting in this forum. My doc is sitting in (our local) HIV guidelines committee and locally plays a role similar to Dr Gallant in the US, providing usefull insight the local groups/associations/activists/govt.
He is no guru, but treating people with HIV and other STD's is his turf...

I need to says this, because I was offered what he, himself, once, nicely called an 'atypical' regimen. and many might thing he is completely NUTS.

Since then, I also found out that I am the first one HE initiates on this combo, and, inadvertently, understood that he initiates OTHER people on different combos (depending on their profile)

I also found out that he follows up a lot of 'old timers'. This gives him some perspective about long term efficacy of a combo, in particular, this one.

We had everything covered with in-depth interviews, blood analysis, close follow up etc. and if it were not for that extended time to UD, I'd say everything went right on.

I am not an advocate for my combo.
I simply relate my own experience and happy to share with others using the SAME combo, in order to provide the prospective user a better feel

On the other hand, my previously reported slow decay in VL could (falsely, IMHO) be interpreted as a lack of virological efficacy and this would do a disservice to the combo, as well as its current or prospective users.

If you read this thread as a prospective user, what does MY slow decay in VL means something to YOU ?
(and, incidentally, as concerned individual, does it mean something to me?)
Should you be worried that my personal experience transposes to yours ?

NOT reaching UD is bad news: it is called virologic FAILURE... a would warrant a switch.
Is reaching UD slowly some semi-failure ?

Time-to-UD
**********

The concept of Time-to-UD (the length of time between initiation of meds and and the moment ones' VL becomes UD)
is to be taken with caution. because its significance it NOT the same whether you look at it from a global/statistical level or at an individual level.
Look at it this way: rich nations have poor people, and poor nations have some ultra rich people. Statistically, it is better fortune to be born in a rich country. But, individually speaking being the son of Mr Multimillionaire of a poorer nation can be quite fortunate as well.
So statistical and personal perspectives are different

Because the history of HIV meds started with meds that were moderately potent (so that HIV was not entirely suppressed and a residual viremia occurred, hence resistance, etc.) and as new meds were introduced, it became quite obvious that the shorter the time-to-UD for the first cohort to use the new combo for the first time, the better.
Therefore, after crunching all these data from all these patients, the-faster-to-UD-the-better concept emerged (for assessing a new product or delivery method or dosing).
The current golden standard is Efavirenz.

All this under the threat of dreaded RESISTANCE.

This is supported by the fact that early mathematical models have predicted that the rate of decay correlates to first approximation with the drug potency.
Of note, these publications date back to 1998-2003 (for the very latest major paper), at a time where under-potent drugs were still in use.
For example:
http://www.ncbi.nlm.nih.gov/pubmed?term=9192676
http://www.ncbi.nlm.nih.gov/pubmed?term=11734232
http://www.ncbi.nlm.nih.gov/pubmed?term=12660935
http://www.ncbi.nlm.nih.gov/pubmed?term=9727569

Hence, after reading all theses post, gladly announcing : started XYZ and became UD in 2 months! , started ZYX and became UD in 3 weeks !!!. etc.

I was looking forward to the UD status, eager for it, anxious for it, desperate for it !

Well, my personal history gave me time, much more than I wanted (to be honnest), to reflect upon Time-to-UD.

And came to the conclusion that the faster-to-UD-the-better-golden-rule may need to be revisited or at least nuanced or put in the perspective of context.

See... I am moving slowly, very cautiously into the argument.
That is because it is so easy to jump to conclusions. (and I hope to avoid controversy)

First, let's bear in mind that, at least where I live, underpotent meds (e.g. AZT) have been phased out and any new med's potency is checked before approval.

I was initially very attracted by Isentress + truvada (and was very upset to hear that our socialized healthcare guidelines does not offer that option for treatment naives, here, whereas it does in the US)
That was because, statistically, Isentress + truvada gets you to UD faster, so, I thought, quite naively, that it is virologically superior.
If the faster-to-UD-the-better is taken as a golden rule for choice, then, this is a quite obvious thing to assume.

Except that, viral load dynamics are a little more complex than I initially thought...

Dr Siliciano, himself, reviewed the issue here, in 2009 :
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980788/pdf/nihms246009.pdf
and concludes: (I cite from the above article)
viral dynamics produced by different antiretroviral drugs should not be directly compared with each other.

He discusses here that it is the very nature of the inhibitor's mechanism and its earlier position (and intervention) on the time line of viral duplication in the cell that will mechanically lead to a faster decline of VL and NOT because of some a virological 'superiority'.

Therefore the recent need for a better definition for drug potency than just the rate of decay.

Several candidate surrogate indices have been proposed such as instantaneous inhibitory potential (IIP) or the inhibitory quotient as predictors of antiretroviral efficacy.

The issue is still currently (2010 Nov 1) fiercely debated as can be seen here:
http://cid.oxfordjournals.org/content/51/9/1105.2.full.pdf+html

More recently, experts have developed a concept of med's potency index. It is a fairly a new concept (2009 Dec) and it is developed here:
http://www.ncbi.nlm.nih.gov/pubmed/19837466
and better developed in this free article:
http://www.iasusa.org/pub/topics/2010/issue3/104.pdf

(side note: I admire Dr Siliciano's work and the way he develops his work and thoughts with crystal clarity)

In my personal understanding, the take home lesson is that if the combo is potent enough to suppress the virus (and fits the resistance profile, of course), the virus gets suppressed.
The 'pressure' is so high that it can't replicate.
If the 'pressure' is enough, it does not have to be more than enough, nor ten times more than enough, nor hundred times (it is a logarithmic scale...)

In that perspective viramune + Epzicom (Kivexa) is potent enough (provided it matches the resistance test profile). It is not the most potent. But its potency is over the required (or recommended) level of 6. (as per the above article)

Since all 'recommended' or 'alternative' regimen (in the developed world) are potent enough, this faster-to-UD-the-better sorts of loses some of its pertinence at the individual patient's level.
Pretty much like the competition for faster cars should be tempered down by the generalisation of speed limits.

The take home lesson is that faster-to-UD-the-better, despite remaining the golden rule, in the absence of a better rule, also needs to be placed and nuanced in the context, EVEN at the drug efficiency assessment level.

Of course, all the above was NOT part of the discussion with my Doc. They are 'starters' or appetizers, if you would.

Because, that discussion I am reporting is not a about the-faster-to-UD-the-better-golden-rule at meds' level but was about patient's level.

Yet, the cautious reader needs to be aware of my state of mind at that time and current scientific context.

I am more than happy to congratulate anyone who reaches the Graal (UD) quickly, but, relating my own experience, would like to convey to those who do not open the bottle of champagne within the first month of treatment that there is no rush (as long as you get there..., though)

This is what my discussion with my Doc is about.

Yet, before I go on, please allow me to introduce another concept.

Time-to-Bed
***********

It is WAY past midnight and Time-to-UD should yield free passage to Time-to-Bed

Stay tuned ! And a happy Valentine everybody !

Eric
« Last Edit: February 15, 2011, 06:43:46 PM by eric48 »
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Latest results: (from first yearly Hospital check up, Blood drawn Jan. 24, that is 7 months into treatment)
CD4 : 680
CD4 % : 35%
CD4/CD8 ratio 1.0  (Yeah...)
VL < 40
Everything else: perfect (cholesterol, blood sugar, anal smears, bone density, lung radio, ECG, mental tests, etc)

The report included some comments that cardiologic risk was very low.
The cardiologist did not provide final conclusions, though, as a stress test has been ordered (because of taking ABC).
This will be performed in May.

The report is 3 pages of data...

The overall conclusion by the virologist was: virologic and immunologic response is optimal

She added that I am still CMV neg (thanks Lady... I'd easily trade HIV for CMV, if you'd want MHO   - LOL)

Doc commented that all lights are on green, not a single one on even yellow.

Could not have hoped for any better.

Doc obviously in good mood.

Still does not have a clue for my jaw clunching effect which is now very light but still noticeable, usually after 5 PM.
Typical anxiety syndrome, he said.
I am still on the small dosage anxiolitic. This is the least addictive they have, I take the smallest dosage they have and only one pill a day.
I just don't like these drugs.



Doc teased me and said he'll put me in a Swiss Alps rehab clinic at his own expense if I can't get off this one...

I just hope he keeps to his word and we can go skying together if I am still on it by next winter.

Transit regularity is almost back to its old once a day.

(I also still suffer a bit of depression, but declined any help he was trying to offer.)

Last but not least:

from now on, he has allowed for taking the 2 Viramune pills together, so now, this combo, is, as far as I am concerned,

ONCE-A-DAY ! ! !
****************

Cheers !

Eric
 

« Last Edit: March 02, 2011, 11:25:43 AM by eric48 »
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline newt

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

Offline J.R.E.

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Eric,

Everything's looking very good for you  :)      !!  I think it was  back in 2004 or early 2005 ( I would have to check my records),  that I was taking both Viramunes together, with the doctors approval.  I only did this for about a month.

But for me, it was just a little too intense, taking both at the same time, especially for the first few hours, so I switched back to twice a day.  But, once again, that was just my experience, and for me twice a day isn't too bad, and is an easy schedule to maintain.



Good luck----Ray
Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline eric48

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  • @HIVPharmaCure & tinyurl.com/HIVPharmaCure
Thanks guys for your continuous support !

It is much needed and appreciated, I can assure you, especially since I also have some concerns (and stress symptoms) with some long term effects of the drug.

A recent article on thebody.com  and my yearly hospital check up gives me the opportunity to mention some of these:

ABACAVIR and Increased Risk of Heart Attack:
********************************************

One of the issue that came up during my yearly check up is the potential increased Risk of Heart Attack when taking ABACAVIR.

as I was being interviewed by the cardiologist, he asked the usual questions about family, use of PI, TG, cholesterol etc.
Yet, the issue of potential increased Risk of Heart Attack when taking ABACAVIR was not coming on the table...

May be he is not aware ? (after all, cardiologists have a lot of stuff to learn to keep uptodate) ?

As we were getting close to the end of the interview, I was getting nervous that we were not getting to it.

I was almost to press the issue when he suddenly said:

"evaluation of your risk profile is one thing but the real thing that I trust is the stress test: that is the real deciding factor ..."

I'll have the test done next month.

So, at least my case is left to the odds of statistical risk calculators

The suspicion of an increased risk associated with the use of ABACAVIR is a quite unexpected outcome of the DADS study.

To make a long story short this large international cohort observational study came up with a number of previously identified risk factors but the increased risk associated use of Abacavir was kind of new and standing out.

The additional risk is a baseline multiplier of 1.9 (smoking is a multiplier of 2 to 3)

I was naturally very anxious and reviewed the issue.
After all, if it had not been for a few posts in this forum I would not have been made aware of this. (Many thanks, BTW)

Here, where I live, people are getting a bit sceptical with our official Pharmaceutical Watchdogs about the side effect and risks, because of strong lobbying from BigPharma that tries to protects its industrial interests.

Big Pharma is not our enemy. But it may be in their financial interest to undertune some deadly side effects...

I went onto our local watchdog administration and found a paper on the issue.
it very conveniently linked to a European document, in English:
http://www.ema.europa.eu/docs/en_GB/document_library/Medicine_QA/2009/11/WC500009006.pdf

Both at our local level and European level, the results of DADS have been confronted with data compiled by the drug manufacturer.

The manufacturer line of defense is to collect all the clinical outcomes of all studies involving Abacavir: no increase of risk was observed

No pathway was identified and therefore the (European) Watchdog administration have decided that no warning note should be issued, at that time.

Let's take this document as a baseline for knowledge at the time it has been issued (2008).

In the mean time, while studies trying to relate ABC to traditional risk factors (LDL, HDL, TG...) failed to produce results, some other statistical surveys have confirmed the additional risk.

Some intresting observations are reported here:
http://www.ncbi.nlm.nih.gov/pubmed/19542863

and
http://www.ncbi.nlm.nih.gov/pubmed?term=abacavir+steal
(of note: An increased risk in cardiovascular disease (CVD) was reported in ABC/3TC recipients compared with TDF/FTC in the STEAL study)

a potential mechanism here:
http://www.ncbi.nlm.nih.gov/pubmed/20453628

Until the actual measurement of my arteries has been performed I can only speculate on 'risk'.

The one study that I found very interesting if this one:
http://www.ncbi.nlm.nih.gov/pubmed/20660842

I found it very interesting because:
- it does confirm a additional co existence of ABC use and additional risk
but also
- it stratifies users based on IDU and cocaine usage. and when stratifying, they find NO additional risk for the non drug user (such as myself...)

There are as many reports that claim this additional risk as they arethat are denying it, that I would not be able to participate in a constructive discussion on that matter.
Since this thread is a source of information to many, I simply report the latest available authoritative news:

Trying to sort out the issue, the FDA MANUALLY scrutinized data provided by the drug trials. It is reported here:
http://www.retroconference.org/2011/Abstracts/42436.htm

The analysis made in the following article is, IMHO, using the most appropriate language to wrap up this potentially controversial issue:
http://www.thebodypro.com/content/confs/croi2011/art60708.html

The take-home lesson is:
************************
- DADS has raised a suspicion for additional risk
- FDA has issued a NEED to be aware and a NO NEED to let this suspected effect interfere with the choice of meds (until further notice).

I would not say that settles the issue, but, helps the prospective user (as well as current user) put things in perspective.

Once-daily
**********
I take it once daily now, and I have even shifted it to the morning. It is real cool! Makes it much easier to manage indeed...
Some adjustment time me be needed though... (I have a had a bad night with tachycardia, very bad sleep, stress, etc...)
I had to buy a weekly pill box with larger container

Sunken cheeks
*************
My doc denied it, but, me, I can see like a hole or shadowed area (depending on light exposure) forming.
It seems benign to me at his point, non symmetrical (it started on one side, where it seems to have stabilized, now the other side has it, but less)
In my age range, it goes quite unnoticed, so, well... let's wait until I fully recover from stress/fear/trauma

Often confused, looking for words, lost in speech
*************************************************
It is most likely a result of depression, stress, overwork, anxiety (work and income), I know..., but it keeps my mind circling back to this issue...

You're looking great!
*********************
I Was at a business convention where I meet lots of people that I would meet only on a yearly basis.
I got commanded so many times (indeed, about a dozen) on how fit and healthy I look that I can't help thinking by myself : if you guys knew the truth...
But, hey, I took it as it came. As a compliment that helps me go through this ordeal.

Once again,
***********

many thanks all for your kindness (and nice PMs)

Cheers ! !

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline Inchlingblue

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Did you see the results of a recent study that found no link to abacavir and increased risk of a heart attack?

Offline J.R.E.

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Did you see the results of a recent study that found no link to abacavir and increased risk of a heart attack?

That would be this one Eric:

http://www.poz.com/articles/HIV_abacavir_heart_FDA_761_19965.shtm



OOPpps..... Link not working See next post




Ray
« Last Edit: March 19, 2011, 09:40:01 PM by J.R.E. »
Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline eric48

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Hi,

If you are refering to the FDA poster at CROI 2011, it is the one  I am refering to in my post here above.
Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline J.R.E.

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FDA Analysis: No Increased Heart Attack Risk While Using Abacavir


by Tim Horn

Can't get the link to work above


There is no association between the use of ViiV Healthcare’s nucleoside analogue abacavir—found in Ziagen, Epzicom and Trizivir—and heart attack risk, according to a new analysis conducted by the U.S. Food and Drug Administration (FDA), reported Monday, February 28, at the 18th Conference on Retroviruses and Opportunistic Infections (CROI) in Boston.
In February 2008, at the 15th CROI, also held in Boston, a review of data from the Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) study indicated that abacavir was associated with a 90 percent increase in the risk of a heart attack. Six months later, data from the Strategies for Management of Antiretroviral Therapy (SMART) study pointed to a quadrupled risk of a heart attack among those using abacavir. Other analyses seemed to confirm these findings, whereas some studies failed to document any connection between past or present abacavir use and heart attack risk.

Despite the conflicting data, Epzicom—once listed as a “preferred” nucleoside reverse transcriptase inhibitor for use in combination with other antiretrovirals in first-time treatment regimens—was stripped of its preferential ranking by the U.S. Department of Health and Human Services in the November 2008 issue of the federal treatment guidelines, partly because of its possible association with an increased risk of heart attacks.

The FDA has now chimed in with an analysis of its own. The agency’s investigators—known for their strict review of data—analyzed the results of 26 randomized clinical trials involving abacavir. Cohorts, including D:A:D, were not included in the agency’s review, given that it is difficult to adjust data from these studies for confounders (undocumented factors that can skew outcomes).

All studies were conducted between 1996 and 2010 and involved 16 pharmaceutical company clinical trials, five AIDS Clinical Trials Group studies and five studies conducted at academic centers. A total of 9,832 patients were included in the analysis: 5,028 of whom received abacavir, and 4,804 of whom received a competing agent.

A total of 25 heart attacks were documented among those taking abacavir, compared with 22 of those not taking abacavir. According to statistical analyses conducted by the FDA, the difference in heart attack risk between the two groups was negligible and not statistically significant: 0.008 percent.

Even when the agency excluded clinical trials in which no heart attacks were reported—18 studies had at least one report of a heart attack—there was no statistically significant difference between those taking abacavir and those not using the drug.

“A meta-analysis conducted by the FDA based on [randomized controlled trials] did not show an association between increased risk of [heart attacks] and use of [abacavir],” the study authors wrote. They added that only a new clinical trial, specifically looking at heart attack rates among those using abacavir-inclusive regimens compared with those using non-abacavir drug combinations, can settle this controversy once and for all.

Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline eric48

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Taking the 2 viramune once a day has really improved my life !

While I may have a bit more of anxiety, now that I have moved the pills to the morning, on the long run, I think I will feel better.

Before, I was taking 2 x a day (one at 7 AM one at 7 PM, along with Kivexa/Epzicom). My stress session would usually start at 5 PM, and even with the light anxilotic, I could have some problem sleeping.

Now that I take it all (that includes moving the Kivexa time) at one time (8 AM), I have noticed that:
- I am a little more tensed during the day
- My stress session will start at 3 PM, take the anxiolitic (sometimes 2 as it can be a little more intense), but less difficulty to get to sleep
- constipation can be quite long 2-3-4 days !

but, for the first weeks in more than 6 months, I have had a few days already with ZERO stress session: gone, nada...

it is a little bit easier too, since Kivexa (aka Epzicom) is a larger pill that require a mouthfull of water, so I usually carried a tiny bottle of water, just in case...
Taking it in the morning, makes it easier.

This time, I am very hopefull that I can have more days without the stress session, which, otherwise was daily ... and depressing.

Somehow, I pretty much understand what Ray meant by saying that the change to 2 viramune together with the Kivexa was too intense for him. But, because there are days where I do not feel anything at all, I hope for the best and like it better this way.
I just need time to adjust.

Or do I ?

May be, I can get the extended realease sooner than I would hope for since the New Viramune XR Tablet has just been Approved for Once-Daily Use by the FDA

http://www.aidsmeds.com/articles/hiv_viramune_xr_1667_20144.shtml

We, guys, will get it a bit later (typically 6 months to a year) since our socialized health system will drag their feet, especially since the manufacturer will want a bit more money for the extended release version.

The great thing about taking it in the morning, it that I do not have to think about it the entire day, do not have to carry pills (I still do, just in case I do not get back home for sleep ;-)  )

Once daily is SO COOOOOL ! (I could do without the entire virus shit, of course...).

I suppose it will be a larger pill too... We will see...

Eric

NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline pozoz

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Eric,

I had a good feeling I would see you write an immediate reference to the media release about the new ViramuneXR...

I found it interesting, especially as I am now taking the "old" Viramune "off label"(2 a day at once with Truvada)

The studies seem to show a slight disadvantage to someone like me. Like you I also  have to wait probably 6 to 12 months to get the new ones.

I wonder , from reading this, maybe if I should revert to the one AM, one PM dosing, although since starting I have only done the 2 at once except the 14 day lead in doses. What do you think ??

I have  a LFT soon(2nd one) and am having absolutely no side effects AT ALL, which is really nice..it's nice not to have the occasional bloating, "D" , and other GI issues I had while on PI's.... and taking just 3 pills with dinner is very easy...hopefully soon it will be just 2 pills, once a day!

Glad to hear your doing well ...  stay well my friend...

Seroconverted Aug 2008
Tested Pos      May 2009
May 09 CD4 544 19%   VL 22K
Aug 09 CD4 514  19% VL 25K
Dec 09 CD4 510  20% VL 32K
June10 CD4 502  20% VL 36K
July 5th,10 Start Truvada  Reyataz Norvir July 30  CD4 360  21% VL 339
Oct  22 CD4 459  27% VL 191
Jan 2011CD4 561 33% VL U/D <40
Feb  Add Verimune lead in dose to start switch to Verimune/Truvada  
Mar 17 Viramune x2 + Truvada. Stop PIs   
Apr 29     CD4 528 33% VL U/D
July 2011 CD4 440  %?  VL U/D
Sept 2011CD4 620  %?   VL U/D
Dec 2011 CD4 531 31% VL 224
Jan 2012  CD4 576 36% VL U/D
May 2012 CD4 504 36% U/D (start Viramune XR
July 2012 576 (36%) (test request due to XR issues)
Feb  2013 629  (? %) U/D
July  2013 608 38%.   U/D
Jan  14.    576  36%.   UD

Offline J.R.E.

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Somehow, I pretty much understand what Ray meant by saying that the change to 2 viramune together with the Kivexa was too intense for him..


Eric




Hey Eric,...



Maybe I should clarify a little.  At the time when I was taking both Viramunes together, I was also taking Dapsone and Zithromax.  So basically, I had a lot of shit  going on back then.  My tcells were also less than 200 at that time.

I guess it's kind of hard making a determination, as to whether the two viramunes together,  was causing this "intenseness" , or if  the combination of Dapsone and Zithromax, may have caused some additional side effects.

I probably would go ahead and try once again to take both of them together again, along with the Epzicom,( now that I am off that other medication) if the doctor thought it was Ok.  I never thought about asking again about it, since things are going along fairly well. 

 If I decided to do it that way, I would take them both at 8:00 in the morning, since I would be going to bed, about 3 hours later.  I work the graveyard shift.  I could probably handle that now.


Anyway, once again good luck !!


PS:  Be careful of that constipation.  Have you mentioned that to your doc?   2-3-4 days, is too long.


Ray  8)
Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline eric48

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I just want my life be like before...

I'm bored with the meds, with the worries, with the sluggish economy, with the wars and disputes.

work, clients, tax fillings, bills, pharmacy, meds, casual (gay) sex are just a necessity of life, that are just getting harder to get along with.

Today was a bright sunny day, spent some time with W, had coffee in our favorite spot, discussed new books, some shopping too...

I was feeling so good... The rest of the day, I fought against the lack of energy and brain fog.

Got back to W and felt good again. Opened a bottle of Champagne and other nice bottles I have. Got drunk.

I 'm drunk and crying. I was the happiest man on earth. I just want my life be like before...

The brain fog was horrendous. I 'm drunk and crying. I know I should feel happy and blessed, but no more the happiest man on earth I used to be.

I just want my life be like before... I just want my life be like before...



 
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline pozoz

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Eric I can relate to this totally and I'm feeling your pain...

I think we all have days like this...the whole HIV/meds/blood tests/doc visits blah blah blah gets very tiring and consumes our lives...it sucks...you are not alone , please be well and keep on keeping on......
Seroconverted Aug 2008
Tested Pos      May 2009
May 09 CD4 544 19%   VL 22K
Aug 09 CD4 514  19% VL 25K
Dec 09 CD4 510  20% VL 32K
June10 CD4 502  20% VL 36K
July 5th,10 Start Truvada  Reyataz Norvir July 30  CD4 360  21% VL 339
Oct  22 CD4 459  27% VL 191
Jan 2011CD4 561 33% VL U/D <40
Feb  Add Verimune lead in dose to start switch to Verimune/Truvada  
Mar 17 Viramune x2 + Truvada. Stop PIs   
Apr 29     CD4 528 33% VL U/D
July 2011 CD4 440  %?  VL U/D
Sept 2011CD4 620  %?   VL U/D
Dec 2011 CD4 531 31% VL 224
Jan 2012  CD4 576 36% VL U/D
May 2012 CD4 504 36% U/D (start Viramune XR
July 2012 576 (36%) (test request due to XR issues)
Feb  2013 629  (? %) U/D
July  2013 608 38%.   U/D
Jan  14.    576  36%.   UD

Offline Inchlingblue

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eric, reality check time: you live in a country where you have health care regardless of whether you have a job or not, right?

That in itself is enough to be thankful for.

I have insurance and I get my meds but if I lose my job I lose my insurance and I lose my meds and I would not qualify for ADAP.


No universal health care here in the good ol' USA.

Offline surf18

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Ah I think were all entitled to a melt down. Eric has good points in his melt down.
Some times a good pity party helpful

Offline eric48

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Sorry for that guys ... That should not have happened and I'll refrain from whining again and concentrate on treatment aspects.

I am trying to keep this thread serious and informative for the prospective and current user user as, I think, there may be more use of this combo in the future.

For example, this once somewhat demoted combo (in the US, the world's opinion leader) is now listed among preferred in London.
http://forums.poz.com/index.php?topic=37089.0

More use, not only for treatment naives but also for treatment experienced patients as part of treatment simplification and cost effectiveness.

For that purpose, I have to document myself a lot, check information before posting, so each post is concocted with care.

The other day I came across some very counter intuitive thoughts that were in the back of my mind from the very beginning of the process. So I kept thinking about the concept and, while my daily life is pretty much back to normal when I am at work and not alone, the stress and brain fog comes back when I am left alone (at the office during the week end).

Some fears can become obsessive and ruin the day. Statistics about treatment failures and percentage of infected fellow humans not able to reach / maintain UD. became obsessive and I was hoping a good drinking would solve it and 'reset' my CPU (it usually works for me). I ended up depressed and (stomach) sick.

Lesson learned. And once again, sorry for that...

induction-maintenance strategy
******************************

The counter intuitive idea comes in the context of modern treatment options. in days past I guess people had to take what was there, on the table, at the time (AZT) and move up to more efficient/convenient/etc. meds, if they could. Or, on the other hand, in case of treatment failure, move to complicated, intrusive regimen.

Times have changed and now there are 'treatment options' which leads to a new paradigm and issue: which one to choose ?

We have a number of stats and analysis that help select a treatment of choice for a given patient profile.

I am not an advocate for this combo in particular, but given my profile and concerns, my doc suggested this one, which, after some initial surprise, I made it MY (educated) CHOICE.

Someone else might have a different 'preferred', some other have no choice...

Some can come to this combo as part of a plausible scenario such as: started on Atripla, moved on to NVP + Truvada if they could not stand EFV, then switch to Epzicom due to some problem of their own with Truvada.

They would end up being, reluctantly, a pill buddy of mine out of 'bad luck' (seen from their initial perspective).

Because there is a choice of option, everyone has a number 1 preferred, then a less preferred, etc. Leading to the possible frustration and fear for a Switch.

In any case, treatment selection, an important phase of the process, is made usually like this:

Your Doc: Given your profile (resistance, sex, lifestyle, ...) I recommend A
sometimes gives you a focused choice (A or B)
You : OK ...

A (of which you might have never heard of until then) becomes your PREFERRED choice.
And the last thing you want is to FAIL on this preferred choice (some of us do not mind so much, but, I would rather think it is a common thinking)

Therefore Doc initiates you on A (your, or his/her, preferred choice)

Makes sense.

And you are anxious about SE and looking forward to become UD ASAP. And here again, you are made anxious to SUCCEED on the initial choice.

So, for modern day, early presenters, with open options, this is a common route.

Your steps are:
1 - selection of preferred
2 - initiation
3 - lots of labs
4 - Fail or Succeed (until you eventually fail, may be 1, 5 or ten years later, or never ?)
5 - switch (to less preferred, unless a better combo comes to the market)

Your doc initiates you on the 'softest' and hopes for the best and leaves it to the odds of your own DNA/destiny and your new companion's RNA.

Seems to me (from reading this forum) the most common strategy.

But given that early failure (within the first 2-3 years) is far from uncommon ( 20 % ?), IS IT the BEST TACTICS ?

I had questioned my doc about this, initially, why start from 'softer' to 'less soft' and not stamp the bug like crazy with 'strong' stuff, at first, then try a softer combo ?

I believe he thought I am really twisted (played pool too much, I guess)

Now that I am so happy with the combo, the fading SE, the once-daily, the labs, I have a new source of anxiety: stay on it as long as possible.

and the conterintuitive (obsessive) thoughts, is that, may be, in order to optimize my chances to stay longer on MY combo of choice, I should not have started with it at first, but rather schedule-switched to it.

Make the switch the ultimate GOAL and NOT the punishment/failure correction

What has revived this conterintuitive strategic thinking is the current switch by POZOZ:
http://forums.poz.com/index.php?topic=36800.0

and the reading of this:
Could Switching HIV Therapy Early Avoid Treatment Failure?
http://www.aidsmeds.com/articles/hiv_treatment_switch_1667_20181.shtml

and the original article:
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0018204

So, while I was expecting that this combo would make it back as a fashionable first line strategy, I am wondering if it would not find a better place in a more comprehensive, scheduled induction-maintenance strategy.

As far as I am concerned, it is too late, I am on it for as long as my new companion stays dormant.

I have no question that this combo was tailored to my profile.

Whether my current initiation strategy was the best, only time and research will tell...

A bit of recent flue like and fatigue raised my anxiety level, being left in the blind until next blood test...

But I am feeling better now. The weather is fine and had some nice 'encounters'

Cheers!

Eric
« Last Edit: April 08, 2011, 07:33:22 PM by eric48 »
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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No big news, but something I learned in reading :

A "New" Antiretroviral Option Quietly Enters the Market
http://www.thebodypro.com/content/art61670.html

(while the article reminds that NVP is (usually) (*) not for women
CD4 counts >250 cells/mm3 and men with CD4 counts >400 cells/mm3
I remind here that this is true for treatment NAIVEs ONLY. The European Agency has lifted that ban for treatment experienced ) (* usually, or normally, whatever... since my doc disregarded this recommendation and initiated me to NVP eventhough my Nadir was 440, I never had a lab below 400)

What I did not know is this:

...the possibility of nevirapine coming off patent in 2012 (which creates potential for a lower-priced generic)...

I think a generic already exists but not sold in 'rich' countries

I suppose it can be a matter of consideration for switch / maintenance strategies

Cheers!

Eric

(note: constipation GONE / stress fading (noticeable but bearable), but, muscle twitching up and depression is up too...)
« Last Edit: April 27, 2011, 06:08:52 PM by eric48 »
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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moderate signs of sensitive axional neuropathy
**************************************************

For months now I suffer from lower leg muscle twitch. It simply never stops. 24/7
I have not mentioned it before because it is benign and often associated to stress, which I have all the symptoms of. (although I suspect it is the meds...)

I went to a lab for an electromyogram (?) where they measure nerve responsiveness.

I have been diagnosed for moderate signs of sensitive axional neuropathy, with no functional neuropathy.
The doctor, there, commented that it may explain the twitching, although he sounded very doubtful.

When the electricity ran through my legs some of the reactions where more sudden than the doctor expected:

Me: sorry for that... I 'm a little tensed
The doctor : Oh ! ? Are you ? I had not noticed , LOL

I'll have a blood test and stress test at the cardiologist soon, then go to my doctor and we will see what he says.

Otherwise, physically speaking I 'm OKAY. I have a stye (I am remodeling and there is a lot of dust around), no big deal I suppose.
The neuropathy thing has been a matter of concern for a few days, but honnest, I do not feel anything at all.

I have a hard time staying awake at work, which my doc says are signs of depression.

Taking the meds is just easy enough and full part of my routine, now.
I am not as worried as I used to be. The tension on the jaw is always there, but, slowly, slowly fading.

Recently, I have been reading a bit more about the latest breakthroughs in science that may lead to a functional cure, which I now believe will come sooner or later.
I have caught myself day dreaming about the cure, retirement or becoming a grandfather, and , why not ... a BF.

The economy is no fun, my work is no fun, aging is no fun. I guess that is what I need : FUN.

That will come... But, first, I have to finish that tax report on my desk (I hate THAT)

Cheers! Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Side effects: lower leg muscle twitching (stress ? ), tension on the jaw, still detectable, but really very close to the unnoticeable threshold.
Constipation: gone, sleep good most nights (w/o sleeping pills)

went to the lab for blood tests then Went back to the hospital for the cardio stress test, which is part of the yearly check up.

The cardiologist in charge was in pretty good mood as he saw me painlessly perform the bicycle test. As the break makes is harder with time some people have to stop before the end of the test.
But every thing went fine. I guess they see a number of people sent in with serious heart condition, which must be quite depressing.

Got a clean bill on that one and said that there is no reason to investigate any further. I did mention that the reason for concern was the Abacavir I am taking, which he confirmed he had seen on my file.
He said everything was as nominal as possible and could not be any better, so I should feel reassured. Good...

The blood test results came back the very same day (that's fast...).

cholesterol/LDL/HDL/TG/Blood sugar/glycated hemoglobin/all minerals/vitamin D/complete liver panel/etc.

Everything came back nominal (e.g. LDL: 130 / HDL: 70 / TG: 56 /A1C: 5.3%)

Now, let's scroll down to the hardcore stuff:
CD4 % : 30
CD8 % : 40
CD4 : 640

So that is same as last December (a little less than January, but January test was not done in my usual lab...)
CD4 count is slightly down, which does not worry me because a plateau in CD4 recovery between months 6 and 12 is not unusual
(at least, this is what is explained here:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC25839/?tool=pubmed
figure 3)

Then came the unexpected number : the VL ...

Since treatment target is 50, our hospital detection limit is 40, I was not expecting the commercial lab I am using to bother much further.
My last VL (in this lab, in 12/2010) was 48, which I thought simply meant below 50 (and we do not bother go any further)

In fact they do... They use a Cobas Taqman. I did not bother ask how low it is supposed to go. I think the latest version (is it 2.0) must be going as low as 20, now that I have my lab results in front of me...

One would hope that, at long last, I would read something like UD, or <20 or 0 (the hospital reports it as 0, which, I was told means below 40)

Well... NO !

If you listen carefully, you still hear my virus vanishing into blue sky, faint signal, but still detectable as it came back as:

VL: 24 !

I got really thrilled, as this comes pretty much in line with the slow, logarithmic, decay which is a personal characteristics of my own case.

It's like seeing the last waiving hand from a train window as it is disappearing in the sunset.

I just hope it travels with a one-way ticket...

Cheers

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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I have commented hereabove that 650 is kinda low (compared to previous values)

The aim of treatment is to restore the immune system as close as possible to its pre-infection state.
Problem: I have no idea what my immune system  was like...

So the closest substitute is to see if it restores as close as possible to normality.

Problem: What is a normal CD4 count? (the most common stratification seems to be <200; 200-350; 350-500; >500)

I have been looking through the Intenet and found various answers including on this (well documented) site, but I wanted to find some more scientifically solid information.

This question because I read the following comment from famed Mari Kitahata, MD

http://www.thebody.com/content/confs/croi2009/art50496.html

I quote:

... a threshold of 500 -- which, remember, is not near normal -- is associated with significant improvement overall ...

referring to 500 as being a stratification for a safer zone,she had commented:
500... is NOT near normal.

Then what is normal ? and more over what is 'normal' and relevant to me (and to some extend to the reader)

Doing my homework here below are a few findings I made and which I can back up with the relevant, freely accessible, medically sound papers

Normal and not normal
*********************

Normal would refer to values in a population that does not present a pathology
Target (or aim of treatment) can be different.

For example, the reference range for non diabetic person A1C is less than 6.5 % (values may differ depending on location, age, doctor, etc)
Yet, a diabetic who is able to take control (insulin, etc.) and has a A1C of 7% would be deemed as 'normalized', because, given his/her condition, this is very good.

This to say, that, in the discussion below, I am not implying that 500 is a target or that 350 is below target or what so ever.

The discussion is about how the medical community (as a whole, not only HIV specialists) define a normal range.

But what is KNOWN about CD4 count in HIV negative population ?

A side note before I start: I have read in numerous posts, here, that CD4 count may vary greatly, as much as 100, during the day (morning/evening)
I have not found any reference to this, when looking through scientific papers.
Nonetheless, it is quite obvious to me that the instantaneous immune profile snapshot may depend , for a while, on one's current state of health (fatigue, stress, small illness, pregnancy, vaccination ...)
I have personal evidence that the same lab, on the same person (me), on the same blood draw, ordered by 2 different doctors, came back with a total lymphocyte count differing by 5 %.
So one has to be carefull when comparing one's data to the reference range.

Okay, back to
the reference range...
**********************

What is known (and documented below) :

- young children, teens, adults (young and less young alike), elderly are different clusters
- ethnicity plays a role and reference range may be different in various part of the world and/or broadened in areas with more ethnic diversity
- females have a slightly higher value
- sports/no sports does not affect much the statistics
- smoking and chronic (benign) infections affect the absolute count and percentage.

Most people do not know their CD4 count prior to infection (one post in this forum mentioned a value of 800 for someone how had a preinfection value due to some other condition (transplant?)
Which is why the reference range is of importance, in the absence of prior values.

Ethnicity/localisation/socioeconomics
**************************************
Let me put this out of the way quickly. The relevance of Ethnicity/localisation/socioeconomics is clearly demonstrated in this
freely available paper:

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702009000300013&lng=en&nrm=iso&tlng=en
(Reference range for T lymphocytes populations in blood donors from two different regions in Brazil)

There are not too many reliable, free sources of data around...
So, it is not the aim of this post to clarify this point in detail, for every situation.

If the reader does not mind, I have therefore concentrated my research on finding data on people that match my profile most.
Anyone is free to look for data matching his/her profile most.

You might think that the reference range would appear on my lab sheet (as do cholesterol, TG, etc). This is not the case.
This lab has a large clientele of HIVER and avoiding publishing a reference range demonstrates a sense of tact.

Being White male in a favorable socioeconomic environment, the freely available dataset which I found closest to my profile is the data published by Italians in hematology papers:

(An Italian national multicenter study for the definition of a reference
ranges for normal values of peripheral blood lymphocyte subsets in healthy adults)
http://www.haematologica.org/cgi/reprint/84/6/499

The article is free, very detailed and based on large, consistent database.

It explains how the data was collected and how the reference ranges (for Italy) was determined.
Similar data are available for various countries, I suppose. This one, at least, is freely accessible.

Mean and Median values
**********************
One has to be a bit carefull here: some articles refer to the mean value and others to the median value.

the (arithmetic) mean is calculated by summing the total of all values and divide by the number of individuals.
The median this is value at which 50 % of the population is below and 50% is above. It is the most probable value you will find if you blindly pickup someone in the street.

If the distribution is perfectly Gaussian and symmetrical, the mean = the median
if it is NOT the case, then the mean and the median are different (the median being lower)

When mean and median are similar, it does not matter much and one can be taken in place of the other. (the non-symetry effect is less visible if the population (cohort) is small)

When looking at a broad population, as being done in the above paper, and in the case of CD4 it is obvious that the distribution is NOT symmetrical

Wheres it is possible that someone may have 2, 3 times the mean values (i.e. the mean plus one or 2 times the mean), it is impossible to have negative counts.

In other words if the mean is 100, it is quite possible to find people with 200, 300 , but not with -1 or -100 (at least certainly not in the general population of the living ;) )

For this reason, whenever available, one should rather look at the median value (the most likely value) and use the mean, only when the median is not available.
 
results for an Italian of my age (M and F) is:
***********************************

Median (the most likely value) CD4 is 885.

The reference range for CD4 count is 496-1666 and for CD4 % : 32-61; median CD4 count is : 885
The reference range for CD4 count is 224-1112 and for CD4 % : 14-43; median CD4 count is : 511

The most graphic evidence is given here:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851216/figure/f1-blt-08-118/

and comes from an other Italian paper:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851216/?tool=pubmed

Side note: since the lower limit of the range is 496, it is quite obvious where this stratification 'magic' number 500 comes from.

Is 885 the most probable value I had prior to infection ?

Not quite... It would require that I correct for gender, smoking status and other conditions...

Which I will do in a next thread

I need to go sleep, I'll count CD4s to help, 1 CD4, 2 CD4s, 3 CD4s,...

Sweet dreams !

Eric
« Last Edit: May 21, 2011, 07:54:00 PM by eric48 »
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Offline eric48

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The reference range for CD4 count is 496-1666 and for CD4 % : 32-61; median CD4 count is : 885
The reference range for CD4 count is 224-1112 and for CD4 % : 14-43; median CD4 count is : 511

Sorry for the typo and too late to modify... One should read:

The reference range for CD4 count is 496-1666 and for CD4 % : 32-61; median CD4 count is : 885
The reference range for CD8 count is 224-1112 and for CD8 % : 14-43; median CD8 count is : 511

Sorry for that... Eric
(I'll prepare something for gender and smoking adjustment next week)
« Last Edit: June 04, 2011, 04:47:28 PM by eric48 »
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Offline eric48

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After adjusting for traditional factors...
*******************************************

How many times haven't we read this generic phrase.

Know this game on TV ? contenders are presented a basket of items and must guess the right price. the closest answers wins...

CD4 themselves come in several subspecies... it a mix bag of naive, memory, effector, what have you...

Based on the above thread, should you pick an adult Italian in the street and been quizzed about this person CD4 count the answer that gives you the highest winning chances is 885 (see median value, table 2).

Now, if you refer to the above article, the TV staff tell you about the persons' gender and smoking status.

Table3  gives the mean values (M: 902 F:989), this is quite consistent with the mean for M+F (940) since (902+989)/2 gives 946. That one is easy since there are about 1 M for 1 F
Men have 44 less on mean value and Females have 43 more...

The article does not provide median values (which are in fact your best bet), but, in the absence of better data, and under pressure of the TV staff, your best choice is to adjust the median value by
44 x (885/940) = 41

Adjusting for gender
********************

You best bet is : M : 844 and F : 926

This was easy enough to calculate because the proportion of M to F is about 1:1.

Adjusting for smoking
*********************

A more tricky one is the adjustment for smoking status.
The mean for smokers : 1044 Nonsmokers: 904, a difference of 140 ! quite consistent with number found in other sources.
This is quite expected since smokers statistically have a higher number of Leukocytes, of which lymphocytes are a subset (source: my doctor...)
In order to win the TV game one would have to adjust knowing the smoking prevalence in Italy.
It is about 25% (source: http://www.ncbi.nlm.nih.gov/pubmed/21421001)
This is quite consistent since:
(1044 x 0.25) + (904 x 0.75) = 261 + 678 = 939 (close to the average smokers+ non smokers of 940)
let's adjust to the median values:
Smokers: 104 x (885/940) = + 97
non smoker= -36  x (885/940) = - 34

So you best bet matching a profile:
Smoker M = 885 - 41 + 97 = 941
Smoker F = 885 + 41 + 97 = 982
nonsmoker M = 885 - 41 - 34 = 810
nonsmoker F = 885 + 41 - 34 = 892

Adjusting for weight
********************

A more tricky one is the adjustment for weight since being overweight significantly increases the values. Unfortunately, the overweight/normal is not clearly defined and its ratio in the Italian population is unknown to me.
some indications can be found here:
http://www.ncbi.nlm.nih.gov/pubmed/21338556
and here
http://www.oecd.org/document/60/0,3746,en_33873108_33873245_46038716_1_1_1_1,00.html

Overweight : 1046
Normal: 926
a difference of 120 !
Let's keep it simple and assume a 20:80 ratio
(1046 x 0.20) + (926 x 0.80) = 209 + 740 = 949 (quite consistent with the mean for all of 940)

Let's adjust the median:

97 x (885/949) = +90 (overweight)
23 x (885/949) = - 21 (normal)

A non smoker Italian male, not overweight most likely CD4 count is : 789 ...

So, if you do not know your pre-infection CD4 count, you can still play the above.

Does it really matters ?
*************************

Not really, since diversity is in the essence of mankind and someone who is 4/11 (1.50 m) is just as 'normal' as someone who is 6/3 (1.9 m) tall

It does not really matters but it is FUN!

(and please do not sue me on the above, it's just a guess game)

And if you like FUNNY, yet serious reading, do not miss:

CD4saurus Rex & HIVelociraptor vs. development of clinically useful
immunological markers: a Jurassic tale of frozen evolution.

http://www.translational-medicine.com/content/pdf/1479-5876-9-93.pdf

It is well documented, entertaining and helps put in perspective the classical strata <200; <350; <500; > 500

"We don't do body counts”. (General Tommy Franks)
"We only do CD4 counts" (My doctor)

We sure care about counts !

Have fun

Eric
« Last Edit: June 25, 2011, 08:12:04 PM by eric48 »
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Offline J.R.E.

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Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline newt

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Except the study in the link is underpowered to capture rare events like heart attack *perhaps* associated with abacavir.

I have no doubt abacavir is an equal option to tenofovir in terms of viral suppression in most cases, albeit with different risks and benefits. Someone somewhere needs to square the findings on abacavir and viral load from other studies and increased risk of heart attack from DAD (the only study designed to capture rare adverse events) with other studies not demonstrating these outcomes.

In the UK, well London, abacavir is first-line, preferred over tenofovir now, except for people with high risk of heart attack, viral load of 100k or more or who are potentially allergic. This is on the basis of cost. It seems a fine enough solution.

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

Offline eric48

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Thanks guys for chiming in... This article sounded like some sort of a revenge for the 'demoted' and a confirmation of my doctors hunch that it would make its come back...

this other article:
http://www.thebody.com/content/62704/abacavir-agonistes.html

helps understand why there are two clusters of peoples:
- those who have recently been proposed to start this (once demoted) combo, and because of various reasons, may feel very uncomfortable with this one combo
(that would include myself)
- those who have started this combo long ago and are apparently doing very well (such as Ray and a few others who have contributed)

A new cluster are those switching to this combo for simplification/maintenance, etc. The reports on this forum have been very positive.

There is so few patient testimony about this combo that I hope this long winded thread may help fill the gap.

Abacavir / Nevirapine and cancers:
**********************************

Strangely enough the DADS study that triggered the unexpected ABC cardiovascular controversy also confirms the (expected) positive effects of NVP.

- NVP has a propective effect and the proposed pathway: it its up-regulation of HDL
- ABC a a 'suspected' (and contested) negative effect, and no pathway has been proposed.

Go figure...

The interesting thing is that 2 other little known benefits (pathways) of NVP and ABC have been observed by researchers:

Both NVP and ABC have demonstrated strong efficacy in fighting some cancerous cells:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782444/
The anti retroviral nucleoside analogue Abacavir reduces cell growth and promotes differentiation of human medulloblastoma cells

which concludes: ... that the use of ABC, [...] could be an effective therapeutic strategy, alone or in combination with current therapies, for the treatment of telomerase expressing tumours, such as human medulloblastomas

http://www.ncbi.nlm.nih.gov/pubmed/19152342
Nevirapine restores androgen signaling in hormone-refractory human prostate carcinoma cells both in vitro and in vivo.

they both are considered as potential efficient drugs in fighting some cancers (including the quite common prostate cancer)

It is therefore intriguing that the observational DADS studies has not, thus far, shown any such effect.

But for the 'older'(male) individuals (like yourself and myself) and propective users, this may be worth knowing

Thanks again

Eric
« Last Edit: July 08, 2011, 06:21:53 PM by eric48 »
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My doctor ruled abacavir out as a possible med for me. Although I passed the sensitivity test, he ruled it out for several reasons - 1) my age (48), 2) a history of hypertension in my family, 3) being a smoker for around 30 years and 4) I have mild Reynauld's (a circulatory issue). I'm going to have to quit smoking one of these days. :-\
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Offline J.R.E.

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Thanks Matt and Eric !

Ray
Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline eric48

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Dr Paul Sax concludes in :

http://www.thebody.com/content/62704/abacavir-agonistes.html

-----
It seems advisable to avoid using abacavir in patients with high cardiovascular risk if there are suitable alternatives (which there usually are), but that stable patients already on the drug should remain on it unless there’s a compelling reason to switch.
-----
This patient (me...) opinion is indeed that one has to feel confident about the ticker before starting treatment. I have experienced very sudden drops in in BP or acceleration of heart beat for the first few months. I was quite scared... So scared. Its gone now, but I vividly remember the tough times.

While it seems reasonably acceptable to postpone treatment initiation based on CD4 and VL history, because these are still strong medication anyhow, it is also reasonable to think that the first few months can be physically and emotionally demanding... Sometimes I think I could have waited a few months/years.
The more I think about it the more I think people who prefer to delay treatment have a point.
But, whatever health issue you may have, you damn want to get it undercontrol (and hopefolly behind you) before you turn 50. After that, it just gets tougher to recover or adjust.

Yesterday my son got his university entrance exams results. He passed with honors.

I hope he can make it all the way through MD. He says he wants to become a virologist... We will see...

I need to keep going for another 10 years to see that happen.

If he does, I am quite sure he is going to be quite shocked  when he meets with his first patient. LOL

Cheers ! (this cheerfull note being dedicated to my son, who, BTW, is also a real cuttie)

Eric





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Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #86 on: August 03, 2011, 07:13:28 PM »
Adjusting 'normal CD4 count' for other health conditions
********************************************************
(A follow up to:
http://forums.poz.com/index.php?topic=33062.msg481999#msg481999
)

The article here:
A comparative method for processing immunological parameters: developing an "Immunogram"
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851216/?tool=pubmed

states:

Furthermore, it is possible to search for associations between different groups of immunological parameters [...]; associations between immunological parameters and positivity or negativity for viral infections (EBV, CMV, HSV, VZV, HCV, etc.) can be revealed; and associations can be searched for between immunological parameters, life styles, current and previous therapies, vaccinations, etc.

In other words that it should be possible to go further into adjusting for other health conditions

There is currently intensive research trying to link the status of immune system to emerging/occurring/resolved cancers.

Pretty much like some viruses, it is hyposized that some cancers have 3 phases:
- initial mutation that create the seed cancerous cells
- identification (or not), eradication (or not) by the immune system, resulting in either elimination or steady state low grade survival of cancerous cells
- if successfull to somehow survive the immune system, further mutates until able to escape and grow exponentially (bad news...)

Some viruses, as well, live in steady state equilibrium with the immune system, which is able enough to control the virus at the expense of ongoing immune system activation.
Eventual immune system exhaustion leads to rupture in the steady state and virus winning over. (our cherished virus being a good example...)

this is why there would be a possibility that some cancers behave in a similar fashion:

While most medical research aims at restoring the immune system to a normal level the article here:

CD4saurus Rex & HIVelociraptor vs. development of clinically useful immunological markers: a Jurassic tale of frozen evolution.

http://www.translational-medicine.com/content/pdf/1479-5876-9-93.pdf

(which is real fun to read)

strongly invites not to look only at CD4 count restoration a healthy ('normal') level, but also at the preinfection level (which is unknown)

I have therefore digged into the available medical literature for existing work that would allow to adjust the preinfection Immunogram to preexisting or coexisting infections.

In other words if it is statically sound to adjust the 'normal' CD4 count (median : 880 for an Italian adult, for example), for gender, smoking, overweight status, is possible to adjust for other known infections (VHC, VHB, etc.)

Thus far I have NOT FOUND ANYTHING, and the announced Immunogramma software does not seem available on line (as of Aug. 2011)


Why Adjusting for known factors may become more important in the future
***********************************************************************

IMHO, it may because more important for the patient in terms of meds initiation decision.
Those years where the recommendation for starting meds was CD4 <200 it did not matter to evaluate if the immune system is damaged by 10, 20, or 30 % because it is in fact severely damaged. Period.
As the trigger value raises (350, and more recently 500) it matter more as the higher the value the weaker gets the medical consensus and the higher gets the patients involvement into this decision, obviously.

As long as the trigger value is 200, it does not matter if you are an overweight, (white), smoker female (median adjusted CD4 count: 1072) or a slim, non smoker male (median adjusted CD4 count: 789), because 200 is low anyway.

but if you consider 500 as your decision or trigger value, and that your most likely preinfection CD4 count (after adjustment) is 700, damage is only 30 %
but if your most likely CD4 count (after adjustment) is 1000 damage is already 50 %.

For overweight, (white), smoker female a trigger value of 350 is 30% of her 'normal' value (damage = 70%) whereas the same trigger is 50% of 'normal' for a slim, non smoker male (damage is 50%)

Using the same initiation thresholds for women and men (as it is in socialized healthcare) may bias treatment decisions more favorably to men and the consecutive delayed treatment for women may account for the surprising higher loss of life expectancy, in successfull HAART, for women as compared to men.
  
Just some thoughts...(and sorry for this long development)

Eric
« Last Edit: August 03, 2011, 07:53:14 PM by eric48 »
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Offline eric48

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UD ! (at long last...)
« Reply #87 on: September 21, 2011, 05:56:31 PM »
UD ! (at long last...)

With VL at 24 (May  2011, 11 months into treatment), there was no doubt this was coming!

It has been a long wait... I guess I should raise a flag or wear a badge of some sort (I bought myself red shoes instead)

(the wait has been sooo long, I guess my sparkling wine has no bubbles anylonger ...)

as of Sept 19 2011 (15 months into treatment)

VL < 20 (Taqman Cobas)
CD4 : 738 (37%)
CD8 : 678 (34%)
CD4/CD8 ratio: 1.09

Everything else (cholesterol, sugar panel, liver panel, vitamin panel, what have you..) WITHIN range.
(only CPK stands out at 554, we will see what Doc has to say about that...)

Neuropathy diagnosis in the legs has been reversed after reexamination by another (HIV experienced, this time) neurologist (who had put me on vitamin B12 three months ago). Note: this B12 worked magic on me!
No sign of no-nothing he said !
(the exam was a bit long and I bursted in tears towards the end, which he said THIS is something I definitively need to address, he was kind of shocked because he knows of all the good news, but still I could not help it)

Constipation under control (thanks to lots of fibers and good advise from this forum)

So it is UD , UD , UD ! ! !

CHEEEEEEEERS

Eric

PS: My strength lies solely in my tenacity. (Louis Pasteur)
« Last Edit: September 21, 2011, 06:03:29 PM by eric48 »
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Offline J.R.E.

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #88 on: September 21, 2011, 06:07:42 PM »
 :)

Fantastic Eric--Great Numbers !!!!


Cheers---Ray  8)
Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #89 on: September 21, 2011, 06:13:06 PM »
Thanks Ray,

I knew you would chime in. Been thinking of you a lot lately.

I owe you one for your continuous support!

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline Inchlingblue

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #90 on: September 21, 2011, 08:15:39 PM »
wow Eric, congratulations!

I'm confident you will continue doing well (based on your thoughtful approach and the fact that you live in a country that offers it's citizens health care).

Offline Assurbanipal

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #91 on: September 21, 2011, 08:29:01 PM »
Congratulations Eric!  It has been a long wait for you.

A
5/06 VL 1M+, CD4 22, 5% , pneumonia, thrush -- O2 support 2 months, 6/06 +Kaletra/Truvada
9/06 VL 3959 CD4 297 13.5% 12/06 VL <400 CD4 350 15.2% +Pravachol
2007 VL<400, 70, 50 CD4 408-729 16.0% -19.7%
2008 VL UD CD4 468 - 538 16.7% - 24.6% Osteoporosis 11/08 doubled Pravachol, +Calcium/D
02/09 VL 100 CD4 616 23.7% 03/09 VL 130 5/09 VL 100 CD4 540 28.4% +Actonel (osteoporosis) 7/09 VL 130
8/09  new regimen Isentress/Epzicom 9/09 VL UD CD4 621 32.7% 11/09 VL UD CD4 607 26.4% swap Isentress for Prezista/Norvir 12/09 (liver and muscle issues) VL 50
2010 VL UD CD4 573-680 26.1% - 30.9% 12/10 VL 20
2011 VL UD-20 CD4 568-673 24.7%-30.6%
2012 VL UD swap Prezista/Norvir for Reyataz drop statin CD4 768-828 26.7%-30.7%

Offline eric48

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Neuropathy: to be (in pain) or not to be...
« Reply #92 on: September 30, 2011, 06:33:02 PM »
Neuropathy: to be (in pain) or not to be...

During winter I started having pain along the leg nerves and had a hard time sleeping.
I talked to my doc who ordered a nerve test at A neurologist. Which I did. I was really feeling the pain, not a fake.
On top of that, I have muscle twitching on the legs which is VERY visible, 24/24, 7/7 since Aug.2010.

That neurologist did some test with needles, etc... and diagnosed: moderate signs of sensory neuropathy.

With this in hand was referred to THE head-HIV-experienced-neurologist. The interview followed a very unexpected path:

A- he said that the neurologist who performed the first test is a nice guy who does not know his ankle from his knee.
B- he was NOT going to pursue the issue until I have gotten the nerve test by his favored neuropathy specialist (he said there are hardly a handfull of doctors in the entire continent who can really diagnose neuropathy...)
C- when I told him I was put on viramune + Kivexa because of the supposed better blood/ brain barrier penetration, he went into some sort of a tantrum, saying this belief (of my doc) is pure BS...
D- I ventured into discussing B12 vitamin (something I had learned on this forum ...): he silenced me right away, saying that he had already included B12 supplementation on the prescription he had on his desk for me.
E- he ordered Vit B1 , B6, B12, E dosing, saying that was just in case, because the 'limits' are not well identified anyway
F- said that my neuropathy (if any) was more likely due to my sub clinical diabetes than HIV.
G- As I was whining about the slow VL decay (I was not UD at the time...), he said "you might just be better out this way altogether, as faster decay goes alongside other problems down the road"
H- was ecstatic about my numbers/blood panel/labs.
I- in this mind, V&K is not known for being neurotoxic, and I should be fine with this 'eccentric' combo
He waved me off with a prescription for B1/B6/B12/E panel (which came back within 'range'), a new nerve test and B1/B6 + B12 oral supplementation.

A few months later (during summer) I noticed that I was noticing nothing at all: the nerve pain gone (the better wheather may have helped)

On the day I went for the nerve test by his favorite colleague, he happenned to be in the lobby. I was so relieved by the disappearance of this nerve pain that I kowtowed dutyfully.
He commented that, while most HIV specialist will not believe in the benefits of B12, he, being old timer, old school, believes in it and was happy it seems to work for me.

Then I got the new nerve test.
 
It lasted for more than one hour (a little more than I could handle and bursted into tears after one hour of being martyred by this (cute & young) doctor into a modern day San Sebastian).
This one concluded that there is no such thing as the faintest sign of neuropathy.

He scolded me somehow for being over sensitive to the HIV diagnosis, that I should move on etc. etc. (I wished he'd hug me tight, but, that, unfortunately, did not happen...).

Wrong diagnosis, better wheather or beneficial B12 ? I 'll never know, but at $ 5/month for B12, I'll stick to it for a while.

Cheers!

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #93 on: November 12, 2011, 04:48:50 PM »
My quest for further information in order to adjust 'normal' CD4 (and other markers) range to the patient's specifics has NOT been very fruitfull. <shrug>

Transient changes in Immunogram:
********************************

The immunologic response to an acute infection results in a such rapid expansion of CD4 or CD8 or NKs that the proportions of each populations can be drastically affected

If interested in the changes induced by an acute infection you may want to read this:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912311/pdf/1471-2334-10-205.pdf

I may, in a previous post, have sounded skeptical about the usual comment that CD4 count can vary significantly during the day, as I had never found any reference to this in the scientific literature.
Somehow, I may have make it sound like some kind of urban legend among HIVers.
To be truly honnest, I have recently found a study that describes the phenomena with a scientific approach.
It was done in a specific settings, yet, it seems a good enough reference:

Timing of blood sampling for CD4 T-cell counting influences HAART decisions.
http://www.ncbi.nlm.nih.gov/pubmed/21991752


Profound changes in immunogramm resulting from a chronic condition:
*******************************************************************

A chronic condition establishes a steady state between itself and the immune system fighting it.
The 'ennemy' evolves to overcome the immune system (or at least establish a stable 'frontline' until it can find a breach)
As a response, the immune system evolves to overpower the intruder and adapt to the successive attacks from the enemy.
We are, after all, the 'healthy' carriers of multiple viruses, bacterias and sub-cancerous cells that are potentially dangerous but are kept in check by the immune system.

This is quite complex and her is a good ppt presentation
http://www.cancer.gov/cancertopics/understandingcancer/immunesystem/

Especially page 20... Furthermore, CD4 and CD8 come in various subspecies (memory, naive, effector...)

It is now widely accepted that chronic steady state with some viruses, mainly ubiquitous herpes type viruses, affects the relative composition of these subspecies,even in the general population.
See:
http://blogs.poz.com/joseph/archives/2011/10/hiv_and_herpes_virus.html
or
http://blogs.poz.com/joseph/archives/2010/03/cytomegalovirus_othe.html

While there is now abundant literature about how they can affect the subset and hints that this may affect healthy aging, there is quite little about how they affect the CD counts themselves

The only reference I could find is relative to CMV.
****************************************************

CMV is highly prevalent among HIVers (as high as 98% in some cohorts) and not harmfull per se (for the immunocompetent adult).
Nonetheless, the very few who are CMV negative should know that CMV negative individual have generally speaking lower CD4 and lower CD8 counts that their CMV positive counterparts
The numbers (but not the subset) tend to come closer as we age, yet the difference is quite significant and very graphically documented here:
 
Differential effects of age, cytomegalovirus-seropositivity ... on circulating T lymphocyte subsets:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024293/?tool=pubmed

The interesting part is on hte 'healthy' controls (not the patients with renal complications)
The most interesting data is in table2:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024293/table/T2/

for a younger person (20-40)
--------------------
CD4+ :   490 if CMV-   860 if CMV+  (*)   
CD8+ :   230 if CMV-   420 if CMV+

(*) very close to that 880 value used a few posts up

for an older person (>60)
--------------------
CD4+ :   630 if CMV-   630 if CMV+ (thus, identical)      
CD8+ :   220 if CMV-   340 if CMV+

(note: the number of individuals in this study is rather small, it should be used with caution)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024293/figure/F1/
diagram A and B provide the age related trends.

At my age (about 50), the CMV neg, (otherwise healthy) person has a CD4 count in the 600s vs the 750 for a CMV+ (otherwise healthy): that is still a difference of 150 !
and CD8 is 250 vs 400

The difference is even more dramatic for a younger person !

As I am CMV neg, I wished I had known this before making the decision to go on meds!

(Well... my age was the real deciding factor, but still !)

I haven't found much more and I guess this may be my last post on this issue.

I hope that the few posts above will be of some help to those readers interested in understanding what is a 'normal' count, adjust to their specifics, see how far off they are before and after treatment...

Later, I'll explore if there are options to tune up the immune response

Cheers!

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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A B! it is a B!
« Reply #94 on: November 13, 2011, 04:12:00 PM »
A B! it is a B!

Pill buddy on this thread, who had been stable for many years, got a UP in VL a few month ago , but back to UD now!

It is a Blip !

I can share the sense of relief, but, honestly have never doubted this combo (nor his adherence to it).

People at the clinic where kind of implying (they never say anything final, 'cause you never know) that people who are stable under this combo seem to remain on it sort of forever.

Except for the very first months (which can be considered risky) it seems there there are only few drop outs.

This is one of the reasons I preferred this one (which, at the time, was a bit demoted).

I was dreading a switch, but with the mental issues (anxiety) I keep having, well... I do not know...

At least the good news is : It is a Blip ! Buddy ;-)

Which raises another interesting question: can a blip be voluntary (and safely) triggered ?

(a personal research subject I am currently actively pursuing...)

Cheers ! Cheers! cheers!

Your Friend, Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #95 on: December 05, 2011, 06:22:23 PM »
Blips and reservoirs are a hot topic !

At least the venue for the upcoming conference held by the experts in the field seems a nice place to gather in these times of cold weather and budget cuts...

http://www.informedhorizons.com/persistence2011/index.html

Hope we will get more than just nice pics of CD4s resting on the beach!

(I was planning to go, until I noticed that Dr Robert Siliciano is not a listed speaker....)

Eric
« Last Edit: December 05, 2011, 06:50:03 PM by eric48 »
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #96 on: December 29, 2011, 06:42:14 PM »
A bit more on 'normal CD4 counts'
*********************************

I wrote that I would not come back to the aspects of what 'normal' CD4 count is, but, in the interim I found a free available article which seems to have been the reference article on this, some 20 years back. The values in that article and the discussions are worth mentioning, at least for their historical value.

it can be found here:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1554313/pdf/clinexpimmunol00049-0059.pdf
Laboratory control values for CD4 and CD8 lymphocytes...

Tweaking treatment ? why bother?
***********************************

Let's move on to 2 subjects of interest, now that I have finally entered phase 3 of viral decay, that is the one where the virus is UD but remains in reservoirs.
(and find my way to phase 4, the actual eradication)

One is: can treatment be tweaked towards better immunologic recovery. Better CD4 counts, CD4/CD8 ratio, etc.
and the second is can treatment be tweaked towards further reservoir reduction

Whether the above is, or not, of any clinical impact for hivers in general is beyond my point here.
Admittedly, as long as you make enough $$ to live decently, what is the point in earning more (optimizing one's revenues)? after all... (*)
As long as you reach and maintain UD and have decent numbers, why bother?
(*) easy for me to say, as I have just earned by highest annual income ever, by far, and, waoh, it does feel good ;-)

One of MY reasons this that I want to enroll into a trial.
 
So whether this is worth sharing here, I do not know...
I have not yet discussed it w/ doc.

When cure (or cure ersatz) or efficient treatment optimisation will be introduced (as a result of current research) Hivers are going to be stratified into 3 categories:

A- those who are faring 'better', and are good candidates for 'cure trials' (see:
intensification trials)
B- the vast majority who are doing OK
C- those whose response to treatment is somewhat unsatisfactory, are in medical need, and are candidates for alternative or intensification trials

Looking at currently published trials I do not qualify for C-trials
(the Berlin patient was in group C...), but I do not qualify for A-group trials either
As an example I may not have qualified for the Sangamo BioSciences trial that identified a good responder, aka the Trenton patient.
http://www.aidsmeds.com/articles/HIV_Cure_Trenton_1667_21525.shtml
(then follow the link to the NYTimes article)

I have already been busted out of one trial because I applied too late (I was already 8 months into infection, 6 was the max)
And I can not enter one I am interested in because my application would be too early as 3 years of being UD (defined as <50) are required, and only one (small) blip allowed! (I only have a documented 11 months below 50, no blips)

I have already entered a personal 'tweaking' project and my next blood test (in 3 weeks) will let me know if it was worth the effort and if I should move on to the second project I have...

Thank-you notes and PMs.
*************************
I would like to thank those sending me Thank-you notes and PMs. They are always appreciated! It helps keep this thread focused.
It also helps me keep working on it

Farewell 2011
*************
How did you like 2011 ?
Somehow, I am looking forward to turning the page of 2011. 
I hope 2012 will be better (for every one!)
(I doubt I can make the same huge bonus, but, hey, I don't need it, anyway)

Stay tuned : 2012 will be a lot of fun!

Happy New Year ! ! !

Cheers

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline J.R.E.

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #97 on: December 31, 2011, 08:12:28 AM »
Eric,..

Wishing you a Happy and Healthy New Year !! About 15 hours and 50 minutes till 2012, here ! It's champagne time again!  :P



All the best-----Ray  8)
Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline cubwolf30

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #98 on: January 05, 2012, 12:04:38 AM »
Hi... first of all, best wishes in this 2012, and well, I want to say my thanks for this thread as I'm possibly beginning my treatment taking a regimen with Abacavir (in 2 days I'll get the results of the gene test), and reading your experience has put to rest some of my anxiety. Thanks again!
diagnosed at 19/03/2003 (from 12/2002)
Starting meds at 1/2012
cd4 7/03: 726
      4/04: 365
      4/05: 580
      4/06: 574
      5/07: 398
      7/07: 515
      6/08: 450 - VL:1700
      2/09: 455
      1/10: 510
      7/10: 439
     12/11: 317

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #99 on: January 30, 2012, 04:53:58 PM »
Hi,

Here below are my latest results (Jan. 23 2012):
CD4 : 777 ; CD4 %: 30 ; CD8 %: 33 ; CD4/CD8 ratio 0.9
Everything else within optimal range (I forgot : VL < 20 ...)

Discussed (last) remaining issues with doc. Constipation gone, leg nerve pain gone, chest pain gone (actually somewhat back the last few days), still need a tiny bit of anxiolytic every day. All these onsets, then vanishing of 'symptoms' are quite puzzling. They do not seem specifics to the meds, which, he commented, are among the best tolerated otherwise (generally speaking). I believe he says so, because he is following up 'old timers' who seem in good shape with it on one hand, yet, I think he only has a handfull of patients on this 'unusual' combo ...
Discussed about joining a trial, but at this time, nothing of interest, that I would qualify for, is being done, here.

He manually checked my abdomen and lymph nodes. This time I was less tense than usual. Quite enjoying it. A bit disappointed when that exam was over. Wished it had lasted a bit more, I guess...I believe in progress and think there is room for improvement (LOL)

My ways of playing doctor are more fun than his ;-)

Cheers ! Eric
« Last Edit: January 30, 2012, 04:59:42 PM by eric48 »
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #100 on: February 03, 2012, 05:07:43 PM »
Hi,

I had been turned on by the fact my doc spent most of the interview looking at me, hum..., carefully, intensely. I had expressed concerns that my cheeks had sunken a bit. I was a bit defiant.
He said that , being an MSM community doc, he never hesitates to prescribe treatment, that they actually perform in his same clinic and that first justified request will grant me immediate access, no questions asked. Yet, he insisted, that I have to come to realize that aging (and a bit of anxiety) will change my face, eventually. He was adamant that this is not Lipo and that he will keep it under surveillance.
Why did he had to add that my skin and other anatomical features are actually well preserved for our (same) age ? and with that charming smile of his, then ...

<tears>

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #101 on: April 18, 2012, 05:49:36 PM »
Why the Abacavir associated MI risk is so confusing
***************************************************

Reading the original document:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688660/

I have recently realized that I had made 2 big MISTAKES in MY understanding of the MI risk associated with ABACAVIR.

These 2 easy to make mistakes should be demystified.

Turning 50 soon, I was really unhappy to hear about that DADS outcome, given my obsession on that subject (family history...)
Quite naturally, I had second thoughts and somehow wished I had been offered Truvada (which may be a nice drug otherwise, I do not know, so please, do not drag me into a discussion on Truvada itself, this is not the point, here)

Here, I will mention a medication I do not take (Truvada, the most common current alternative to Kivexa), something I usually refrain from, but this is where MY mistake lies.

MY FIRST MISTAKE
*****************

My (false) understanding was to consider that the original DADS shows that ABC demonstrates an ADDITIONAL risk compared to OTHER NRTIs (which in MY mind included Tenofovir and FTC, the components of Truvada, the most currently used combined NRTI) and therefore to think (falsely) that DADS demonstrates an additional MI risk between KIVEXA and TRUVADA.

The truth is the original report for DADS DO NOT demonstrates an additional cardiologic risk of KIVEXA vs TRUVADA.
I though it did, after (wrongfully, my bad...) understanding second hand reports, review and comments or posts on this forum.
But the fact is that the original paper DOES NOT demonstrates an additional cardiologic risk of KIVEXA vs TRUVADA. (the 3TC component of Kivexa is usually considered as being so similar to the FTC component of Truvada, so that the differentiator is ABC vs TNF).

Because this is what the original (first) DADS report says about Tenofovir:

quote: Patients participating in D:A:D have also received other drugs as part of their nucleoside/nucleotide backbone, including emtricitabine and tenofovir.
There is currently insufficient follow-up time (<2 years on average) among patients receiving these drugs to assess reliable associations with the rate of myocardial infarction.(unquote)

In other words Tenofovir is not part of the 'OTHERS NRTIs' category. It is simply not covered by the FIRST DADS original report.

Nonetheless, it is included in further reports (as DADS is an on going follow up study)

http://jid.oxfordjournals.org/content/201/3/318.full

But, here, the authors are very cautious... Because ABC was introduced on the market MUCH before (5 years?) TNF, the data collected do not span over the same period and less data is collected on TNF

As of 2011, there are, to my knowledge 3 longitudinal studies including cardialogic risk evaluation, including ABC, AND VERY LARGE, multi ethnic cohorts. (IMHO, the smaller danish cohort, does not qualify in that definition).
They are DADS, ANRS and VA cohort.

Here below is the comparison table, with conclusions relative to ABC vs TNF (who cares about other NRTIs in 2011...)

DADS : ABC vs TNF : additional risk but to be considered cautiously as TNF was included later.
ANRS : ABC vs TNF : no difference in risk (after screening out IDUs, a potential source of bias effect aka channeling effect)
VA Cohort : ABC vs TNF : no major difference in risk (a slight advantage in favor of ABC, though...)

This was MY first mistake: to think that DADS was CLEARLY demoting ABC vs TNF.

A side note: same caution if you are considering modern PIs that were NOT included in early DADS reports

Duration of inclusion (hence statistical relevance) can not be ignored.

MY SECOND MISTAKE
*****************

was to consider that ABC is multiplying MY MI risk by the (usually referred to) risk ratio of 1.9 (later downgraded to 1.7) (which is almost as high as smoking) (note: the multiplicative risk ratio for smoking is 2 to 3 depending on studies).

Here again this is NOT true. DADS itself points out that the additional risk is VERY HIGHLY stratified per baseline (i.e. pre-meds) cardiovascular risk.

The risk (if any) is ONLY for those with a higher baseline cardiovascular risk (scored, I suppose, on the pretreatment Framingham score-sheet).

The evidence provided by DADS original report itself is EXTREMLY GRAPHIC:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688660/figure/F1/

For those with low or medium baseline risk, the additional risk is hardly noticeable (if any); on the other hand very much associated with the higher baseline risk group


From the (new) patient perspective:
***********************************

If you are offered ABC, your doctor has heard about DADS, and has done due diligence, in particular with regards to baseline cardiovascular risk.

So, do not make the same mistake I made and take it easy.

Cheers, Eric (who still has another cardiologist appointment coming up, just to be on the safer side)
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline Peacock

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #102 on: April 22, 2012, 04:56:19 AM »
Thank you Eric for all your information from the viewpoint of a patient starting Viramune and Kivexa (Epzicom). I found it VERY interesting, especially as Im currently on Nevirapine and the very 'outdated' Combivir. Ive been looking at replacing the Combivir with something else and the choices so far are between Truvada or Epzicom.
Your letters have been informative and great to read, Thanks!!!
Steve ;)
« Last Edit: April 22, 2012, 10:09:15 AM by Peacock »
Peacock,Steve
Diagnosed 07/01/2002
Started Haart- 25/11/04 Cd4: 205 VL: 76'500
                      19/12/08 Cd4: 623 VL: UD
      26/03/12 Cd4: 497 Cd4%: 30.10 VL: UD
Combivir and Nevirapine(200mg) x1 of each-Am & pm
Not changed Meds since starting on HAART
Green Tea,Multivit,Selenium ACE,Folic acid,Vit C,Aciclovir 200mg 5x per day for 3 days-(ONLY when I have Shingles!)
100 percent adherence-with the help of a wristwatch!

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #103 on: April 22, 2012, 05:51:21 PM »
Hi,

Thanks for the comments. Appreciated. (BTW, my PM box receives this kind of nice comments on a regular basis: thanks you all!)

The good news for you is that, since you have tolerated your current combo for long, you can always switch back to V&C, should you find V&T or V&K not of your liking. The switch would simplify your schedule to once daily, which I find convenient, because except for business trips, I do not have to bother about carrying pills. I just keep some spares in car/backpack. The alarm by the bed does the trick for me. I do not even have a wristwatch

I recently found some statistics (which I'll post soon) that support the general understanding about that combo: discontinuation rate is a bit higher than others at initiation, but continuation rate after year 2 seems extremely stable

Be well !  Eric 
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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test results, cute cardiologist and one excellent surprise
******************************************

I knew the test results would be good (but I did not know yet it would bring an additional bonus):
UD (hey, what would you expect?)
CD4:  739
CD8:  738
CD4%:  31,2
CD4/CD8 ratio : 1.0
HDL: 0.70 ; LDL: 1.45, everything else well within range...
No single health issue during this long and rainy winter (except a bit of tiredness, fatigue, lack of energy...)

http://vacs.med.yale.edu/IC/

yielded a 3% 5 year mortality risk (the lowest value that this calculator can provide, given my age , which I can not change, is 2% i.e. if VAcs index = 0)
(I get a slightly higher score (6) due to a lower level of platelets, eventhough, they have increased recently)

Had a bit of discussion with Doc about a few people who had kindly PM'd me and expressed fears about NVP
He said that Doc who are careful in patient selection before choosing Viramune are equally happy than with EFV, that he prescribes EFV more often that NVP, but has had more adverse events with EFV than NVP.

Discussed that I am feeling a bit alone on this less usual combo.
He said that NVP had been banned from some hospital because of patient death, but that was before the screening rules were implemented.
That it also depends on doctors education, experience and confidence, (and availability...) which leads to a situation where NVP is never used in some parts of the country
He said that, on the other hand, there are others regions where V&K is 'hype' and the trendiest thing in town . Patients show up and demand this combo
May be some people are reading this thread after all...

Discussed the new cardiologist who will now be in charge of my 'yearly' check up. Brillant HIV/cardio specialist (wrote books, publications, etc.) and extremely cute, assistant doctor, who is right on my type!
(I wonder if this will show on the cardio test when he performs it...)
Sex drive is back somehow, which he commented was a good therapy... Well... In our offer and demand local gay scene there is little room for courting and romance... So, I am not always very comfortable with my doc 'recommendation' that I should have more (extramarital) activities. I fell like a dinosaur in this sex consumption scene. I prefer to have an open discussion with doc, rather than be offended by comments that are, IMHO, out of the main scope of a doc visit. Nonetheless, my position of a listed (ex-) gay activist who happened to have found happiness with the (most unexpected) person he loves most ( and happens to be of the opposite gender)  is a very sensitive subject. A bit more tact in this matter would be nice, but I think this is way out of his mind set.

The good news
*************
When he gave me the prescription he underlined one new thing:
The prescription is valid for 6 months !!
He said that one benefit of V&K is that once people are stable on it, they are very stable and with this kind of numbers, there is no point in seeing me as often as before.
And that unless something shows up the 'yearly full hospital check up' is from now on once every 2 years!

Boy!.. after all the stress of this fancy combo initiation, here comes the reward
I was not even looking forward to less doc visits (*) and blood work, but, this, indeed will lower the burden by ca. 50%

I have regained a confidence in myself that I though was gone for ever...I feel suddenly much better!

(*) I like my Doc, but with regards to his color matching taste, there is room for improvement

Cheers!

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline nvhorseman

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Doctors have hundreds of patients. To expect them to remember the co-habitation situation of all of them is naive. I'll take brains over social banter any day and be happy with the results of less pills, increased efficacy and stabilization beyond expectations. As a patient, if I were to notice how "cute" my cardiologist was and "just my type", I would be the last to criticize my physician's bedside manner.http://forums.poz.com/Smileys/default/shocked.gif I'd gladly settle for doctor's visits of 2-3 times a year vs. the 6 I endure, especially if I was told I could "date" again. Your physician didn't say to go out and have unsafe sex, he said to have more sex. Now that you are feeling better, I hope you do just that with any consensual and educated person you choose.http://forums.poz.com/Smileys/default/wink.gif The choice is yours, not his.http://forums.poz.com/Smileys/default/kiss.gif

Offline eric48

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Doctors have hundreds of patients.
Thanks  for posting. While this thread is focused on treatment, (especially when on a less common, once demoted, combo) and not about doc and patient relationship, I do not mind commenting on doc patient relationship as it is a significant part of treatment/healing. (and otherwise would be a boring medical thread)

I am more than happy with the choices he has made with/for me thus far. He a fabulous doctor. he's got lot's of good connections.
I have also expressed my interest in participating in clinical trials (and we are doing prescreening tests), but, I'll live the final say up to him.
Doc and I have concording/converging views on a number of issues and discordant on some other.
The 'special' relationship is not on a personal level. It is on a risk management which goes beyond routine clinical care. And I do not mind giving some insights:

Just to give some background, in our local socialized health care, HIV is ONLY handled through hospital. There is no such thing as private practice. This may sound 19th century to a lot of people, especially in the US. Nonetheless, my doc was authorized, on an experimental basis, to open the first ever  (and so far only) private practice in our country (based on his long hospital experience and contribution as a board member of local guidelines). This experimental private pratice is actually partly subsidized (by the state) and he still works at he hospital.

I feel privileged (and gratefull) for the extra care and time he gave me.
That my doc is a more-than-usual important person to me may have transpired through this thread. It is a given fact. My choice. While I have received some PMs asking if I am attracted/in love with doc: the answer is simply NO
Am I a more-than-usual patient to him ? I hope not, I am sure he treats other patients with the attention they deserve according too their specifics (treatment failure, (illegal) migrant status, complication of any sort, etc). But there is a bit more to it:
A- I know for a fact that I am (one of) the very first patient in his all new private practice, and most certainly the first newly diagnosed to be sent to him directly rather than hospital first (as is standard practice here). His other first patients were old timers on follow up. (originally this experimental private practice was started to take some burden off the state hospital and restricted to follow up of 'stable' patients). He did show obvious surprise when I showed up as a newly -diagnosed and his office was still humid with the all new paint and furniture still wrapped in plastic!
B- I am (by far) not the first patient he initiates on Viramune. I am not the first patient he initiate on Kivexa. But the first he initiate on both (his hospital boss forbids that...)

Treatment is a journey. A special one for me (obviously) and also for him (not medically speaking, but as the sole, unsupervised, decision maker, in an entrepreneurial sense)

The (visible) success of his experimental private clinic and of (so far so good) success of my own treatment makes me a special-patient no more.

In a sense, the fact that I am put on the lightest possible maintenance schedule makes me happy, but, sure, I'll lose that special care and doc availability that this 'unusual' combo initiation requires.

Commenting on sex / doc / love (and doc taste in clothes) is normally not part of this thread and I will refrain from now on.

Through this forum and other reading I realize how lucky I am (in a sense): less than 25 % of US Hivers are UDs, and about 50% where I live...

I have just lost a special status (my initial doc visits were twice a month!) and gained a new one ('stable' patient) and I hope the readers will excuse a bit of venting and whining

I also hope that prospective users of this 'fancy' combo will still like reading this one single, no-more-unique patient experience

Cheers and stay tuned ! (I have more on tweaking this combo....)

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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How many of us ?
*************
Hi,

this post:
http://www.thebody.com/Forums/AIDS/Aging/Q221359.html

citing this publication:

http://www.hivandhepatitis.com/hiv-aids/hiv-aids-topics/hiv-treatment/3552-croi-hiv-people-with-cd4-counts-above-500-match-life-expectancy-of-general-population

CROI: HIV+ People with CD4 Counts Above 500 Match Life Expectancy of General Population

and other life expectancy articles are among most popular story on aidsmeds as well. Earlier reports had looked at people with CD4 > 500 AND VL < 50.

Needless to say, for people like myself who could be treated early and have, thus far, been good responders, this is good news.

The stats are one thing and the patient perspective, another.

This less than usual combo (Viramune / epzicom) is not for every one: treatment naives with higher CD4s are excluded, and, since the risk of failure at initiation is higher, may be not for people with low nadir (at least a a first line combo), as they do not have the luxury of time. etc...

Yet one question is rarely addressed: how many of people under long term HAART, in a setting of good availability of care and meds are UD and have CD4 > 500.

This free article here:
Cost-effectiveness analysis of initial HIV treatment...
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234156/pdf/ceor-3-197.pdf

addresses mostly economical aspects.
Yet, it provides 3 very interesting tables:
- Patient distribution based on CD4-cell count and viremia
and mortality...
- Patient distribution based on CD4-cell count and
viremia
-Efficacy data: immunologic response per different treatment regimen
(side note: V&K is not listed, but very close combos such as V&T and S&K are listed: initial success rates is lower but extremely stable over the years.)

When care is available, 'normal' life expectancy (the >500 strata) is for 25% of patients and 'near-normal' life expectancy (the 350< CD4 < 500 strata) is for another 25% of patients. That still makes ca. 50% !

half full or half empty glass depending how you look at it, this is still a very good number considering the nasty nature of the virus...

My doc seems happy with the optimal response to my treatment.
Feeling a bit lonely on V&K, it just makes me feel a bit better about it to learn, that, (where meds are accessible) good response is far from rare.

Cheers!

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Hi,

This thread aims at providing patient perspective for those initiating with Nevirapine (or considering it as a second line)
I try to provide usefull information while avoiding useless controversies.

Publication in AIDS 2012, 26:000–000 :
http://www.ncbi.nlm.nih.gov/pubmed/22546987
The effect of efavirenz versus nevirapine-containing regimens on immunologic, virologic and clinical outcomes in a prospective observational study

as well as comments here:
http://www.aidsmeds.com/articles/hiv_efavirenz_nevirapine_1667_22585.shtml

and here (a subtly nevirapine bashing post by Dr Paul SAX)
http://www.thebodypro.com/content/67311/generic-nevirapine-now-available-but-the-big-one.html

cannot be ignored.

I had access to the original article, way before these comments were published, and handed a print out to my doc.

He had no time to go through it and simply shrugged, saying that these larger multi cohorts are suspicious (same as DADS findings on Abacavir)

I would wish anyone could have a first hand read at the original paper (not second or third hand comments). Unfortunately, you will have to pay to have access to it.

In the next few posts, I'll comment on the virologic, immunologic and clinical outcome restricted to NON-AIDS defining patients that this prospective study is supposed to deal with

It is definitively an interesting story... But the previous ABC DADS story teaches us not to rush to conclusions!

It is also a technically difficult article, yet, I have already identified some methodological flaws, conclusion inaccuracies and computational errors (sic) in the original article...

One thing they did not miss though, it is the TIMING: just a few weeks before NVP patent becomes public domain ...

Well... Let's go through this together one step at a time ;-)

Once we have clarified the conclusions of hte above mentionned publication, I'll post some other interesting and unexpected benefits of NVP that I found (by chance) in an unrelated scientific debate.

Stay tuned

Cheers Eric
« Last Edit: June 24, 2012, 06:07:00 PM by eric48 »
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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The above  article is about the virologic, immunologic and clinical outcome restricted to NON-AIDS defining patients ONLY. All patient with and AIDS defining condition are excluded. Only EFV or NVP initiating patients are considered.

Same as DADS, this is a prospective study... Good as a whistle blower, but prone to analysis bias and interpretation. See:

http://www.iwh.on.ca/at-work/59/retrospective-vs-prospective-studies

Virologic failure
*****************

In this post; let's focus on one of the first conclusion: virologic failure is higher, in this asymptomatic virtual cohort, with NVP than with EFV and let's put things in the patient perspective...

Virologic failure rate is higher in the NVP group. (BTW, it is also in cohorts including all patients). This results is far from unexpected. NVP is often said to have a lower barrier to resistance.

This terminology may be a bit improper.

Browsing through available literature I think there are 2 schools:

Concept 1

NVP is resistant to mutations that are less likely to be identified in an initial resistance test. An initial resistance test can only pick up mutations that present at above 20 % level. If NVP is resistant to a mutation that hovers at 10%, it is not picked up at initiation by the first resistance test.
It is sometimes pointed out that a single dose of NVP can built resistance. then that resistance goes in hiding, behind fitter quasispecies. Upon initiation, what was below 10% now becomes 20 % and so on...(*)

Concept 2

The virus can mutate a lot... The high mutation rate is due to inherent infidelity of HIV reverse transcriptase (RT) and RNA polymerase II and may be partly caused by cellular cytidine deaminases such as hA3G (APOBEC3) (which the virus jams thanks to its Vif factor). If a drug allows for more mutants, and replication keeps going, ultimately, by chance, one mutant will be fit enough and resistant, hence the virologic failure. (**). Bad news for those who experience that...The good news for those NOT experiencing virologic failure though, is that those mutants, that might partly refill the reservoir, are most likely defective. This could be extremly Beneficial for people successfull under NVP 

Therefore:
If NVP initiation protocol would call for a resistance test prior to initiation AND a resistance test within the first few weeks (when VL is still > 500 or 1000 depending on labs)(as I did myself), potential Virologic failure would be identified earlier and the virologic outcome would be better.

Therefore it is NOT NVP, per se, which is the problem, it is the way NVP is initiated and resistance monitored...
(if resistance tests were more sensitive or cheaper, then virologic failure would be less likely).
Here the problem is not the drug itself but the initiation protocol or practice.

Is the take home lesson for someone who initiates therapy in 2012 same as for those who did way back in 2000 in this cohort? Of course not...

NVP carries more risk of VF. Fine. We knew that already. I was really scared myself and this is the reason why I started this thread (BTW)
 
Back in the years 2000 this was a definitive lowdown for NVP (vs EFV), because in case of failure your options were limited. But in 2012, early pick up of VF warrants an early switch to Etravirine (same class) or RAL (INSTI class) or even Maraviroc (if applicable and available)

So the risk is (slightly) higher, but you've got your arse covered.

You are jumping with smaller size parachute, but with a big time safety net (RAL/ PIs/ MVC/Etr) that initiators back in 2000 did not have... Yet, so many times I see posts where people are told: take this pill once a day for 2 weeks then twice daily from day 15 and we will see you in 3 months (sometimes 6...) unless you have a rash.

As a patient you want to be damm sure the airbags are available and will trigger on time !

Sorry for the long post. Next post, about immunologic outcome, will be shorter...

Stay tuned

Cheers Eric

PS: for further reading   

(*)
there are many academic reference for this. Let's just quote:

quote:Our study also reveals that the excess treatment failure observed in the NVP arm is strongly associated with detection of NVP-resistant mutants missed by standard population genotype. (unquote)

from:
http://thomasland.metapress.com/content/5h0rudc88rr7xemj/fulltext.pdf
Role of low-frequency HIV-1 variants in failure of nevirapine...

(**)
http://www.hindawi.com/journals/mbi/2012/586401/
HIV-1 Reverse Transcriptase Still Remains a New Drug Target...

This article has an interesting section of pro-mutation differences between various NNRTIs
« Last Edit: July 15, 2012, 03:48:55 PM by eric48 »
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Offline friskyguy

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Eric

Thank you for devoting your time on this forum.

I am not sure if you can assist here? Are you able to shed some insight re one of the biggest drawbacks to treatment with NRTIs and that is the decrease in mitochondrial DNA which has with prolonged use has been linked to tissue toxicity including premature aging, body shape changes, peripheral neuropathy (PN) and myopathy.

I am aware that Abacavir is not considered as toxic as previously used NRTIs. Well that is the current thinking now.  ::)

Management of potential mitochondrial toxicity during long term nucleoside analogue therapy would therefore remain a challenge for many of us. 

How would one know of any potential underlying cell damage taking place on NRTI treatment before symptoms would present?  If we decided to continue on NRTI treatment, how could we manage the potential toxicity? Would being pro active in including nutritional supplements help lessen the risk of toxicity in any way?

I tried bringing this to my attention of my specialist but he was not able to shed any real light on this topic. I thought that perhaps during your extensive research you may have stumbled across some relevant information.

cheers
Frisky

Sero converted Sept '10 / Confirmed + Dec '10
Jan '11, VL 9,500 / CD4 482 (32%)
Feb '11, VL 5,800 / CD4 680 (37%)
start Atripla
Mch '11, VL UD / CD4 700 (42%)
Jun  '11, VL UD / CD4 750 (43%)
swap to Kivexa and Efav. due to osteopenia diag. (DEXA) / kidney issues ( decline in eGFR to 77 )
start supplements - Vit D3 / Omega 3 / multivitamin / mini aspirin
Dec '11,  VL UD <20 /  CD4 670 (49%)  / CD4:CD8 = 1.4
all labs now within normal ranges
Mch '12,  VL UD / CD4 600 (51%)
Sep '12,  VL UD / CD4 810 (51%)
Mch '13   VL UD / CD4 965 (56%)
Sep '13   VL UD / CD4 (not taken)
Dec '13   VL UD / CD4 901 (35%) / CD4:CD8 = 1.1  /  eGFR > 100

Offline eric48

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Thanks,

One of the above cited article provides in depth explanation about how NRTIs work:

I quote

Importantly, unlike NRTIs, NNRTIs do not require intracellular metabolism to exert their activity...
(unquote)

NRTIs do not have a direct activity, they need some kind of enzymatic transformation and it is the resulting  products that have the inhibitory effect (not the NRTI themselves): hence the mandatory intracellular metabolism

read this:
http://www.thebodypro.com/content/67445/spartan-two-drug-nrti-sparing-strategies-continue.html
and this interesting question:
Do the NRTIs provide some key antiviral component mechanistically?
There seems that (modern) NRTIs have something that makes them unique and, therefore so important, in the HAART weapons.

First, I never (almost) comment on drugs I do not take. Therefore, I cannot state anything on NRTI sparing regimen. Most of them are PI based, and PIs also come with their share of management issues. And depending on the initial resistance test not everyone has the luxury of choice, anyway.

The point that I hope to come to in the next few post, is one key understanding: NRTIs act BEFORE integration of replicate DNA bits in host chromosome, right after viral entry, whereas PIs act at the other end of the cycle, before the exit.

In  layman's words, NRTIs and NNRTIs are trying to prevent the bank robbers (who have successfully passed the entrance door :( to access the vault room, whereas PIs prevent the bad guys to leave the vault/bank

I think you should put your (legitimate) concerns about these long term toxicities into perspective:
Well treated people (like yourself) may lose a few months to a year of life expectancy to HIV + HAART, admittedly. Blue color workers lose 5 years to white collar, and smokers something between 5 and 10 years.
 
As far as I am concerned, it may well take me 3 years to get adjusted to the meds, but I can see things improving one  tiny step after the other. I hardly ever notice it now on facial change or fatigue, etc.

I will have a post dedicated to liver health management, though, as I have found a few things that I still need to confirm and may be usefull to my pill buddies

I am working on some exciting new findings that may inspire hope to people with a treatment profile like yours

If, indeed, this is a manageable condition, then it needs to be understood and managed...

Stay tuned

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #112 on: August 27, 2012, 03:30:51 PM »
Immunologic response
********************

Dynamics of VL decay are much better understood than CD4 dynamics.

Historically, VL decay was thought to be a single phase logarithmic decay
(for those unfamiliar with logarithmic decay, think of radioactive elements such as iode which has a short half life). It was early understood that the decay was at least bi-phasic (a sharp initial decay, followed by a slower one). At the end of this biphasic decay, the virus should have disappeared and treatment could be ended and the infection made history. Unfortunately not the case ...

Dr Siliciano then introduced the concept of a tri-phasic decay (a model later refined to quadri phasic) in which the last phase has such a long half life (44 months) (think of plutonium) that people would have  to remain on treatment for more than an estimated 66 years

Very few models of CD4 dynamics have been offered until this very recent paper:
HIV Model Parameter Estimates from Interruption Trial Data including Drug Efficacy and Reservoir Dynamics
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0040198

- it is free
- the fit between model and clinical data is really convincing
- it offers a CD4 dynamics that is at the same time simple and convincing enough
- it is consistent with the disappointing results of treatment intensification
- it is compatible with Dr Siliciano's model of a slowly decreasing (non replenishing) reservoir
- it is compatible with the alternative vision that the reservoir replenishes (cell-free transmission as well as
A. Sigal 's Cell-to-cell spread (transplication)
http://www.nature.com/nature/journal/v477/n7362/full/nature10347.html

unfortunately:
- it is difficult to understand
- it applies mostly to the context of successfull treatment and good immunologic response

Finally, it offers an alternative vision to the logarithmic decay paradigm, on which very early works were based. A paradigm that has recently lead to set backs in reservoir suppression trials (as it assumes that the reactivated latent CD4 will have a logarithmic decay by intrinsic self death, which they don't, and do not have the
second chance of a logarithmic decay due to an adverse environment, since the milieu has lost its anti-HIV activity, as demonstrated by Pr. Siliciano himself).

The steady state equations are not very different from Pr. Siliciano's system of three ordinary differential equations published in page 3 of:
Low-level HIV-1 replication and the dynamics of the resting CD4+ T cell reservoir for HIV-1 in the setting of HAART
http://www.biomedcentral.com/1471-2334/8/2/

Steady state equations are just easier to understand...

Here is my humble understanding of the equations as these equations are the key to a-cure-within-one's-lifetime; the set (1) of 3 equations is in page 2

They consider the steady state of healthy CD4S (subtly named 'targets'), steady state of infected CD4s and steady state of VL.

The easiest to understand is the last one:

VL equals virus production from actively producting cells minus the clearance rate of free virus

easy enough...
 
(note: residual free RNA, a measurement surrogate for VL, due to dying CD4s are not accounted for since this applies to post-second decay, here, they imply VL = active virus, which is not exactly the VL reported on one's lab sheet)

the second:
infected CD4s are made of recently infected CD4s, plus reservoir (latent) minus dying (infected) CD4s
the number recently infected CD4s, itself, is the number of CD4s multiplied by VL (in other words exposure the active virus) and attenuated by a factor combining drug efficacy and virus infectivity

(of note: it exposes the Dr Siliciano paradigm that drug efficacy, in a successfull combo, is 100% efficient, which regardless of virus infectivity makes that multiplier equal to zero and and therefore equate the number of infected CD4s to the latent, quiescent reservoir only)

Here, the interesting points are :
- reservoir replenishment is zero if infectivity is zero (i.e. CR and/or X4 receptors are successfully blocked)
- a less efficient drug that would hinder more the infectivity (fitness) of the virus could very well lead to less reservoir replenishment (on the next cycle) than a more efficient drug that would otherwise not change the virus fitness (+)

The third:

Uninfected CD4s are equal to their proliferation (++) (birth, duplication, etc.)  minus their death rate and minus those which have been infected

Okay... This is a long and technical post, and not necessarily bullet proof.
Yet this is the necessary base for next post which is about the Nevirapine (Viramune) immulo-virologic apparent PARADOX

Stay tuned

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #113 on: September 23, 2012, 05:52:50 PM »
Hi,

Each drugs has its pros and cons.

Nevirapine, a fairly 'old', somewhat marginalized (usage ca 16%), drug, receives pretty bad reviews and any article showing its relative inferiority (usually vs EFV) receives wide publicity (including on this site). On the other hand there is a growing evidence that NVP has also some very interesting advantages, but those reports get unnoticed.
I have answered about 15 PMs from people so anxious about NVP, who finally did fine...

Let's expose the Nevirapine Paradox and cheer them up!

For the sake of easier understanding, try to visualize a chart or cursor where we scale virologic and immunologic outcome. Some sort of a 'progress bar'

To the left we place virologic failure along with immunologic non-response: bad news. Here, in that area of the chart, well..., EFV bests NVP. The Odds ratio (risk multiplicator) is ca. 1.5 (most likely less now that closer monitoring and screening is enforced, IMHO)

Somewhat towards the right, we place satisfactory immunologic response (CD4 > 350, for example) and VL < 50 : clinically encouraging news.
In that area, differences are almost inexistant and the pros and cons are more in the range of secondary aspects (cholesterol, CNS effects, ease of use, cost...)

Further to the right, we can place the best that we can measure. It is not necesserally clinically relevant, but there is most likely a status better than just CD4 > 350 / VL < 50

And even much further to the right are 'cures' obtained by medication, which would be the Graal of Pharma-cure; (bio-cure is out of the scope of this efficiency chart). (Thus far considered never-reached, this unchartered area is open to research and speculation)

The 'best' we can quantify (with advanced techniques, as of 2012) are:
A- VL =< 1 (Free RNA)
and/or
B- CD4 >= 500
and/or
C- Integrated DNA =< 10 ppm (that is 10 per 1 million CD4s have integrated HIV-DNA)

Patients who are A and B and C are labelled here 'Full responders'.

Since CD >= 500 and VL < 50 seems to confer a minimal additionnal death risk, there is no evidence that Full-responders will fare better than good responders, but, on our chart they are one step closer to the Graal.

Here is as cohort review of 'full responders':
http://www.ncbi.nlm.nih.gov/pubmed/22915460
Nevirapine use, prolonged antiretroviral therapy and high CD4 nadir values are strongly correlated with undetectable HIV-DNA and -RNA levels and CD4 cell gain.

The 420 patient cohort is restricted to patients who are VL <50 within 6 months and remain stable. The above report looks at 'Full responders'. They represent only 6% of patients who maintain UD (patients who are UD , vl <50 is ca. 50% of treated patients in that region). So, full responders represents ca. 3% of patients under HAART .Current combo is recorded to see if some drugs are more favorable. Obviously, in that socialized health care cohort, the newest, most recently approved drugs are not present. Therefore, the statement below does not include these.

With the sole and only exception of Viramune, no 'classical' drug was associated to 'full-reponse'.

Obviously starting treatment earlier and at higher CD4 Nadir makes it more possible to qualify to this group. After all, if your Nadir is 600, it is unlikely that you are to miss one of the 3 criterias (CD4 > 500)...

That NVP is the only drug associated to full-response is already an intriguing observation.

More interesting is the odds ratio: 3 ! this is very high

If you would want to 'rate' NVP vs EFV at the left end of our chart, NVP is 1.5 'lesser' than EFV. but on the other side of the chart NVP bests any other (incl. EFV) by a factor 3

This is what I call the Viramune paradox...

- it is a lesser drug if your fail
- it is a better drug if you succeed.

Why this happens ? is this of importance for moving further to the right (Pharma-cure) ?

Stay tuned and I hope NVP users will enjoy the further developments such as: Is it possible to monitor progress towards full response ? ...

Eric
(Aug. 2012 labs: VL< 20; CD4 : 686 (33%); CD8 : 686 (33%) CD4/CD8: : 1.0)
« Last Edit: September 23, 2012, 06:03:11 PM by eric48 »
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Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #114 on: September 27, 2012, 05:22:43 PM »
It did not make the headlines, but, what follows may matter to nevirapine users.

The 'discovery' or 'smoking gun' proof of cell-to-cell transmission by Alex Sigal is a turning point. It made the headlines.

It has lead A. Sigal to write an interesting (although not bullet proof) 'perspective' in Nature

Underlying this publication is a generation as well as a conceptual quarrel between moderns and ancients, between reasoning by infectivity persistence (Sigal) and reasoning by number persistence (Siliciano)

When I read A. Sigal's 'perspective' article (unfortunately, not free..), I had a feeling it would be hurting the numerists feelings and some strong academic response would follow.

Right on: Pr. Siliciano's just published his 'own' 'perspective'... It is strongly worded and tries to establish dominance of his concepts (it is R. Siliciano's numerist concepts that lead to believe that it would take 66 years, hence life long, to eradicate the virus under current, modern HAART). To make his point Robert Siliciano not only used his remarkable crystal clear style, he also made available for free...

Sigal only marginally mentions Siliciano's work. Siliciano minimizes Sigal's... (*)

reference for reading are here:

Original Sigal findings:(not for free, unfortunatly) Aug. 2011
Cell-to-cell spread of HIV permits ongoing replication
http://www.ncbi.nlm.nih.gov/pubmed/21849975

Sigal's 'perspective': (not for free, unfortunatly) Aug 2012
The Problem of HIV Persistence despite Antiretroviral Drugs
http://www.ncbi.nlm.nih.gov/pubmed/22901535

Siliciano's 'perspective': (free, but...) Sept 2012
Redefining the Viral Reservoirs that Prevent HIV-1 Eradication
http://www.ncbi.nlm.nih.gov/pubmed/22999944

Why this is of importance here? because 'numerist' perspective fails to explain the Viramune Paradox, where as a competition between numerical persistence and infectivity persistence may explain it...

Stay tuned, this is going to be a REALLY interesting academic debate that may change the perceptions that we have about competing drugs long term efficiencies and the (somber) perspective of a never ending treatment.

Eric

PS: (*) added on 09/29:
(R. Siliciano writes: (quote)
An interesting recent paper suggests that in the vicinity of a virus-producing cell, the exposure of adjacent cells to multiple infection events reduces the efficacy of antiretroviral drugs on a probabilistic
basis (Sigal et al., 2011). However, cells with multiple proviruses are rare in vivo (Josefsson et al., 2011) (/unquote)

In fact this last point, apparently silencing Sigal, is not as strong as it seems because Josefsson's measurements where made in blood and Josefsson's conclusion is (quote) our results indicate that most CD4+ T cells in the peripheral blood contain only one copy of HIV-1 DNA (/unquote). He did not write in vivo... he wrote in PBMC... and CD4 in blood are ca 2% of all CD4s... And Sigal already acknowledges that cell-to-cell transmission can (almost) not happen in CIRCULATING liquid (such as blood)...
« Last Edit: September 28, 2012, 07:31:28 PM by eric48 »
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Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #115 on: October 13, 2012, 04:56:03 PM »
So... Why is 'full response' of interest (A) and is there a status even better than 'full responder' (B) ?

A - As per R. Siliciano's above mentioned article: (quote) Eradication efforts will likely be attempted only in patients on HAART who have had sustained suppression of viral replication for years, and therefore the cells responsible for the second phase (+) may not represent a barrier to eradication(/quote)
(+) he refers, here, to residual replication

In other words, any one interrupting treatment at a point on the treatment progression timeline where residual, under the radar, replication has not ceased is bound for... a viral rebound (no pun intended)

Therefore 'full responders' are among the best candidates for the upcoming eradication trials. So anyone willing to participate in an eradication trial should at least be a full responder (or similar). Not convinced? Then browse for eradication clinical trials and look at the inclusion criterias.

And the best way to actively maximize chances to be a full responder:
- long duration of treatment (not under patient's control, recently treated will have to be patient)
- earlier entry into treatment (not so much under patient's control)
- use of Viramune. (a viable option for some patients, but not all...)
(or modern drugs? we do not know yet, since treatment duration is a main key factor)

My point here is certainly NOT to say that NVP is superior to other meds ... I am not interested in dog fights about drugs. I just want to convey to the 'poor' patient who is not eligible for the newest, fancier caviar regimen, and is being scared of this slightly riskier drug, that, on the long run things may turn out much more favorable than expected 

But there is more...

B - on our progress bar, where the 'Pharma-cure' is at the rightmost end, is there any reachable status that is even better than full responder ? Yes there is... The happy few (may not a few as we might think...) are labelled 'secondary controllers'. Ever heard of Secondary controllers ? Most likely not...

These are patients who, generally disregarding medical advise, have interrupted treatment and have had no need (mostly) to resume treatment.
Elite controllers are 'natural controllers'; 'secondary controllers' are patients who were not natural controllers, but who, after years of successful treatment have been rewarded by this 'secondary control' status.

Say, you go by Barré-Sinoussi's definition of a functional cure :
(quote).. (at) least render the need for lifelong anti-retroviral therapy obsolete (/unquote)

quoted from (free) article: Controversies in HIV cure research
http://www.ncbi.nlm.nih.gov/pubmed/22424402

then, it sounds pretty cool...

So, we have this all new video game, where you can raise up from hell, to reasonable health condition, and then move forward to a 'full responder' status then further to that exciting 'secondary control' status, which, from a patient perspective is just wonderfully great. (to date, 5 years off-treatment with clinically good enough control for some patients...)

'Secondary controllers' are a new urban legend ? Is there a clinical trial to back this up ?
Well... I certainly did not make this up !
Skeptical? Then do you own research or just stay tuned for more on that super status and, more interestingly, how it relates to your current or prospective NVP combo and provides more fuel to that interesting Viramune paradox ...

Stay tuned for more

Eric

PS Abacavir users will love the irony of this finding in here:
http://www.ncbi.nlm.nih.gov/pubmed/22994586
Cardiovascular risk factors and carotid intima-media thickness are associated with lower cognitive performance in HIV-infected patients:
... abacavir use was independently associated with a better cognitive performance  ... (no kidding)
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Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #116 on: October 27, 2012, 09:13:41 PM »
A very good definition of secondary viral control is given here:

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0037792
Immune and Viral Correlates of “Secondary Viral Control” after Treatment Interruption in Chronically HIV-1 Infected Patients

The work is based on a small, but well monitored, socialized health care cohort of the Institute of Tropical Medicine of Antwerp, including over 1700 patients. This is more a case report than a clinical trial and one could think it is only anecdotal.

Let's grant those doctors in Antwerpen (Belgium) with an ounce of credibility. HIV is their daily turf. There may be some methodological mistakes in the report, but once again, this is from experienced HIV specialists who are not new to this field.

Once striking number is that about 10% of patients (eligible for free treatment) drop out despite medical advise... It blows my mind, I could not believe it. The younger generation has been 'told' about but has never 'seen' AIDS in action, but still...

Among the drop outs 2.5% have been labelled 'secondary controllers' (4 divided by 160)

Obviously anyone just entering treatment has very little chance to control the virus, thus, it would be inappropriate to think that 2.5% of a given cohort are potentially secondary controllers. On the other hand, it is reasonable to think that among the good eggs who did not drop therapy despite many many years of successful treatment, there are some secondary controllers in the closet. Therefore it is not unreasonable to think that in this particular cohort, ca. 5% are secondary controllers.

Is there something special about Antwerpen ? Why other studies have not picked up those SC ?
Are these fakes ? (people telling their doc they are not taking meds while importing generics on the side ?)
(in socialized healthcare where meds are FREE, why would one want to do that ?)
Are there people out there not telling their docs that they have stopped taking the meds (but with good control, the doc can not find out ?)

Well... That is for those doctors to find out...

This is not a denialist thread (by any means), it is about NVP (and ABC/3TC). What does this have to do with NVP ?
Is this topic going completely out of control ? Without access to patients' treatment history, how can we relate to NVP ? Well... why don't we just try to do that... Hack into the Antwerpen cohort SC's medical history and see the intriguing relationship with Nevirapine (Viramune) ?

We will do that on next post.

Stay tuned for more

Eric

Latest Labs:
Oct 15 2012: VL < 20 CD4: 676 (40%); CD8 : 490 (29%) CD4/CD8: : 1.4 (Yeah!!!)
CD4 count well in line with models derived from above mentioned equations. CD4% jumping from 33 to 40 in 2 months is beyond my expectations... CD8 also may need to be confirmed (potential outlier)
Next Labs around Nov. 15
« Last Edit: October 27, 2012, 09:33:07 PM by eric48 »
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Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #117 on: November 25, 2012, 04:03:27 PM »
Hi,

Nevirapine, the little drug that could:
****************************

Well... We do not really have to hack into people's clinical records...
4 patients have been described and reported as secondary controller.
While my current personal target is full control (as described above), this SC status is very attractive and, IMHO, the closest you can get to a Pharma-cure.
Fortunately, a detailled case report of 2 of the 4 patients can be found here:
Control of viral replication after cessation of HAART
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046910/

Those 4 SC (see above post) are very interesting. They divide into 2 subsets:
Secondary viral control and good immunologic standing (SC+/I+) : 2 patients
SC and less favorable immunologic standing (SC+/I-) : 2 patients

The 2 patients for whom we have treatment information are (SC+/I+) : 1 patient and (SC+/I-) : 1 patient. 3 of the 4 had been on treatment more than 10 years.

Unless I have missed something, here is what adds our final touch to the NVP PARADOX exposed earlier: the 2 patients for whom treatment is known were on ... Viramune!
The studied population is very small and this could be only anecdotal, but, as of today, unless I have missed some other studies, the following seem right to claim:
 
100 % of fully described secondary controller were on nevirapine !...
**************************************************

Considering the usage of NVP is of about 16%, in other words one in six patients, the odds of picking randomly 2 patients in a cohort and find that they are both under NVP is like throwing 2 dice, and get ... a double 6
1 in 36, less than 3 percent. Is this just by chance ?
It can be argued that the numbers are too small to draw a conclusion, yes... but this is intriguing enough.

Still anxious about starting or switching to NVP ? Well, I can understand, but, it is also possibly, one of the best way to get as close as possible to a functional cure

In the next posts, we will see why this might be, and how we can monitor our own treatment progression towards full response and, why not ... SC...

If you would want to learn more about the little molecule that could, I recommend this video

http://us.viramune.com/consumer/viramune/how-viramune-works.jsp 

Stay tuned for more

Eric

Latest Labs:
Nov. 15 2012: VL < 20; CD4: 886 (highest ever) (37%); CD8 : 719 (29%) CD4/CD8: : 1.23 ( > 1 is thus confirmed!)CD4 count NOT in line with my models, but flu shot might be the cause
« Last Edit: November 25, 2012, 04:08:01 PM by eric48 »
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Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #118 on: December 21, 2012, 07:25:44 PM »
Hi,

Very scarce information has been published to date with the combination of ABC/3TC/NVP
This is why I keep readers of this thread posted about news findings.

For people looking for ressources about this combo, there is actually very little. Which may help explain why this is thread is, as of today, the most read in this section of the forums.

Finally, a scientific poster has been published on this combo...
************************************************************
http://www.jiasociety.org/index.php/jias/article/view/18343
Effectiveness and tolerability of abacavir-lamivudine-nevirapine (ABC/3TC/NVP) in a multicenter cohort of HIV-infected ARV-experienced patients

prospective users may want to review it.

Understanding the Viramune Video
********************************
Last post I linked to a video available on the official Viramune Website.
Actually, in an other post, I had given a simplistic and quite graphic explanation of how NVP works
I am posting here this same description as a supplement to the above mentioned video.
I hope it may help understanding that video, somehow

Variability is due to the infidelity of the reverse transcription process.

The NNRTIS (such as Viramune aka NVP, or Efavirenz aka EFV ) block the reverse transcriptase in a geometrical fashion. (also called steric)

To try to explain in layman's word is kind of difficult.

But think like this.

Visualize a hand holding a baseball, then remove the (large) ball.
You hand now has a shape similar to the reverse transcriptase. keep that shape firm

NVP is a small molecule that will geometrically fit between your thumb and first finger, like a small table tennis ball. When the virus DNA approaches the transcriptase, the small ball gets its way. But in some cases it can manage it way through, but not without damage (mutation)

EFV is a larger molecule (like a tennis ball), it fits between the thumb and second finger, thus better blocking transcription process.

More novel NNRTIs are even bigger and fit between thumb and third or even fourth finger, making a complete blockade. In this respect they are more 'efficient'

only one mutation during a faulty reverse transcription can make the virus resistant to NVP. EFV requires two mutations. In that respect as well EFV may appear more efficient.

Nonetheless, mutations have a cost on the virus, which becomes less fit for the next round of infection. Single round efficiency of EFV is superior to that of NVP. but the infectivity of a virus that may have passed the drug (which is not 100% efficient) is less in case of NVP than in case of EFV

The re-contamination rate is combination of infectivity and efficacy
therefore this combination is similar with NVP than with EFV AS LONG AS the number of rounds and potential events for mutation is not too high (in the case of NVP). IF VL is high or CD4 is high the odds that an unwanted mutation appears increases.

Which is why there is a limitation on NVP initiation on both VL level and CD4 level.
The reason why the cut off value is higher in men than in women is a bit obscure.

It may be related to the fact that proliferation (number of newly created CD4s, hence new 'targets') is higher in women than in men, who, in average have a 100 to 150 higher CD4 count (as observed in the non-HIV infected general population)

The above explanation may have flaws and not scientifically rock solid, but, I hope it helps you...

up-coming posts
***************

In the next posts I'll discuss 2 topics that I have been working on recently:

1- a novel method to evaluate in-vivo drug efficiency. This is some work that I am currently documenting and circulating through research community in order to get it further validated. We hope to publish in a scientific publication. Here, I will only give a layman's approach and outlook of what it implies from the patient perspective

2- a tool to allow users evaluate if they qualify for 'full responder' status, even when they have no access to high resolution VL nor reservoir measurements, as these are out of reach in standard clinical follow up.

I hope this will be of interest to those who found some interest in the Viramune paradox.

The little drug that may be a curse for some and a blessing for others as it may help them get to that secondary controller status, which, from a user perspective, might be just as good as a cure.

Last meeting with Doc
*********************
mix feelings. The cardiologist report had not reached his desk, the CCR5 tropism results had not been provided and we suspect an hospital 'miss'.
That was not a good start. We lost a lot of time looking for these missing reports
Yet, now that I have been put on crestor (rosuvastatin) 5 mg and responding well to it, my lipid profile is a winner:
HDL (the good one) 80 (mg/l)
LDL (the bad one) 90

With such good numbers (CD4 , VL, %, ...), he was quite happy!
Me not. I wanted to discuss a few things, which he was not prepared to hear, and so we ran out of time.
So, I have to redo the CCR5 and go again next month.

Cheers

Eric
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Offline friskyguy

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #119 on: January 02, 2013, 12:12:27 AM »
hi eric,

good to hear that joining the small numbers of elite controllers are secondary controllers.

what about the issue of inflammation in both of these groups?

inflammation is the silent killer that wears down our body as the immune system  is continually being on a high state of alert to control the virus.

meds helps us dampen this immune system hyperactivity.

so one might be lucky to be an elite controller/secondary controller and not need meds but if that means that their body is continually in hyperactive mode to control the virus, not sure if that is a good thing for our bodies due to the negative complications to our bodies arising from inflammation?

anyway just throwing it out there.......
Sero converted Sept '10 / Confirmed + Dec '10
Jan '11, VL 9,500 / CD4 482 (32%)
Feb '11, VL 5,800 / CD4 680 (37%)
start Atripla
Mch '11, VL UD / CD4 700 (42%)
Jun  '11, VL UD / CD4 750 (43%)
swap to Kivexa and Efav. due to osteopenia diag. (DEXA) / kidney issues ( decline in eGFR to 77 )
start supplements - Vit D3 / Omega 3 / multivitamin / mini aspirin
Dec '11,  VL UD <20 /  CD4 670 (49%)  / CD4:CD8 = 1.4
all labs now within normal ranges
Mch '12,  VL UD / CD4 600 (51%)
Sep '12,  VL UD / CD4 810 (51%)
Mch '13   VL UD / CD4 965 (56%)
Sep '13   VL UD / CD4 (not taken)
Dec '13   VL UD / CD4 901 (35%) / CD4:CD8 = 1.1  /  eGFR > 100

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #120 on: January 02, 2013, 07:12:52 PM »
Hi,

Thanks for the question. Happens that I have an appointment soon with a cardiovascular specialist, and, since taking ABC, the question will be on the table.
So I hope to get more for you soon...
Back in the old (sad) days, that inflammation question was really invisible, well behind a crucial survival crisis. Even weight gain (a concern for some of us) was way out of scope (in an intriguing article published recently an MD said: where is all the wasting gone ? my HIV patients are getting obese ! (LOL) )

You have several issues and they are difficut to sort and rank:
- the virus
- the virus induced inflammation (or inflamaging)
- are the meds enhancing or reducing this inflammation
- drug (meds) toxicity

My gut feeling is that the Virus is the key and prime problem including in those inflammaging issues.
Clearing the virus is our new target. Maybe we will not be able to eliminate the virus entirely, but we can find hints or better ways to reduce the number of infected cells.

This is a concept very little discussed in the scientific litterature.

When VL is down to UD the disease progression has slowed down. Fine.
But how many (CD4) cells remain infected ? 50% , 25%, 10 %, 1 %, 0.1% ?

From an escape from certain death pespective, if you are starting at CD4 = 10 drug efficiency is more or less defined by the abilty of the drug to increase that number (definition #1). and if that number can slowly go up to 350 who care if X % are monoinfected or moderately infected as long as they can survive and fulfil their role. So from a disease non-progression perspective it does not really matter.

But, an other efficiency definition for drug efficiency (definition # 2) would be the ability to enrich the pool of non-infected cells and reduce the pool of mono or low infected cells.
That definition of efficiency is irrelevant when your strategy is to increase the CD4 cell count at what ever cost
But now that people are initiating treatment sometimes at CD4 600 or even more, that other definition of drug efficacy (the ability to 'cleanse' the infected cell pool)
starts making sense for some patients

I'll document this in a future post.

The '90s or '2000 paradigm was to find an escape route (from certain death)
The '2010s for many people this is still the same
BUT, seen from the 'younger' generation patient, initiating with better meds, at a higher CD4 count (a small fraction, but say even if this is only 1-2 % of patients) it is legitimate to live with the expectation that they are engaging a route towards a cure. And all the argumentation about a phamaceutical cure being impossible can be revisited

I think this is the key to the apparent Nevirapine paradox:
- as par definition #1, other drugs have proven superior
- as per definition #2, a less documented concept, NVP might faring much better

Stay tuned for more

Eric
« Last Edit: January 02, 2013, 07:17:14 PM by eric48 »
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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #121 on: February 24, 2013, 09:46:14 AM »
recession hitting badly. Little time to work on this thread. Will comme back later Eric
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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #122 on: March 25, 2013, 02:42:30 PM »
just switched to Viramune 400 mg XR. pill is a little (ca 15%) bigger than one 200 mg immediate release, yellowish vs white. The change was easy enough, but, somehow makes me feel the Kivexa (which I have always suspected to give me anxiety) is a little harder to get by with.
Well ... I am on anti-depressants and anti-anxiety for treating depression as well. so it is hard to say.

Eric 
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Offline eric48

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Can't kept this for myself...

CD4 : 779 (46%) ; CD8 : 400 (24%) and ... CD4/CD8 ratio : 1.9 !...

CCR5 test came back favorable, which my doc says it is quite common for people who could start treatment early. So at least CCR5 antagonist are an open option.

Why so excited about CD4/CD8 ratio : 1.9 ?

Chomont classification and sieve for identifying patient's with lower active sub-clinical replication

Chomont article demonstrates 2 modes of viral persistence: TCM and TTM CD4+ T cells define distinct HIV reservoirs.
HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation
http://www.nature.com/nm/journal/v15/n8/abs/nm.1972.html

This results in 2 distinct regimes (either steady state or dynamic) as well as, in some patients a combination of both.
This article is not free and not easy to understand...
Fortunately, the supporting data, the table of 34 patients (all with VL <50) is in a freely available supplement. Here again not easy to read unless you type the data into a spreadsheet and plot the data with X axis being CD4/C8 ratio and Y axis being the estimated size of infected cells (in part per million, of CD4)
(because they have been introduced only recently, very modern drugs such as RAL are not found in patient's regimens)
http://www.nature.com/nm/journal/v15/n8/extref/nm.1972-S1.pdf
table is in page 6

The relationship between CD4/C8 ratio and infected poll becomes clearly visible. and 4 rectangles (areas) can be identified on the diagramm.

A- CD4/CD8 ratio less than 1 and infected cell > 200 ppm
B- CD4/CD8 ratio less than 1 and infected cell < 200 ppm
C- CD4/CD8 ratio more than 1 and infected cell < 200 ppm
D- CD4/CD8 ratio more than 1 and infected cell > 200 ppm

Remarkably, there are not a single of the 34 patients in area D, in other word, in this limited, but well studied group, no-one with a ratio > 1 has a pool of infected cells (in blood) > 200 ppm

On the other hand, whenever the ratio is less than 1 relatively nothing can be said, the infected pool can be just anything from 10 ppm upwards to thousands.

This table provides an interesting snapshot, and, while generalization is questionable, it offer an interesting perspective on dynamics. CD4/CD8 ratio is equal to CD4% divided by CD8 %, and is relatively stable and steady, in the same fashion that CD4 % is. It is moving, but not jumping around especially in those patients where CD4 is on the higher end.



Enjoy !

Eric
« Last Edit: May 17, 2013, 07:35:25 AM by eric48 »
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Offline eric48

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Hi,

On the graph above, I have marked in red patients using Viramune. non users are in blue. Two  thirds of Viramune (nevirapine) users have a low reservoir.

Chomont has published a recent article (not free):

CD4 T cell nadir independently predicts the magnitude of the HIV reservoir after prolonged suppressive antiretroviral therapy
http://www.ncbi.nlm.nih.gov/pubmed/22019250

in which he reckons
(quote:)
Previous small studies have reported that HIV-1 proviral DNA levels are inversely correlated with CD4/CD8 ratio or CD4 T cell counts in successfully ART-treated or naïve HIV-1-infected subjects. Our results confirm and further extend these studies showing a negative correlation between the frequency of
CD4 T cells carrying HIV-1 proviral DNA and CD4/CD8 ratio or CD4 T cells, in infected individuals receiving ART and in whom plasma viremia had been suppressed below the limit of detection for prolonged periods of time. (end of quote)

this article also refers to this (older, but free) article
Relationship between the size of the human immunodeficiency virus type 1 (HIV-1) reservoir in peripheral blood CD4+ T cells and CD4+:CD8+ T cell ratios in aviremic HIV-1-infected individuals receiving long-term highly active antiretroviral therapy.

http://www.ncbi.nlm.nih.gov/pubmed/12023777

This other study includes ca. 30 patients. In figure 1 diagram C:
http://jid.oxfordjournals.org/content/185/11/1672/F1.expansion.html

you will recognize the same L shaped scatter plot with the same A, B, C, D areas as on my diagram above (the only difference is that the vertical boundary is, here, at CD4/CD8 = 1.2, whereas in Chomont's data plot the boundary is at CD4/CD8 = 1.0)

In figure 2 (especially the diagram named 'combined') shows that HIV-specific cytotoxic CD8+ T lymphocytes are much lower when CD4+:CD8+ ratios is over 1.2.

Therefore, while the CD4/CD8 is not a absolute surrogate for a low reservoir (one can have a low reservoir and a lower ratio), anyone with a 'higher' ratio
is very likely to have a low reservoir and therefore a good candidate for eradication trials.

In next post we will see the triple play CD4/CD8 ratio, CMV and cancer risk

I hope the above will be usefull to Nevirapine users...

Cheers

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Hi,
Very rarely at at the clinic, would I meet someone looking sick. Yet, last visit was on the day the psychologist was in. The waiting room was filled with people who obviously live with the burden of past medical events or treatments...

To these people, the content of this thread may seem unrealistic and I apologize for that.

Doc visit: nothing special to expect as all numbers are in range (even LDL is low: 0.86). Doc reads the Lab report, he seems concentrated and unconcerned at the same time.

Doc : Whoa... CD4/CD8 = 1.9 (looking happily surprised)
Me : (smiling) right on my expectations
Doc : ??
Me : (smiling as if this was my moment of victory)
Doc : Don't worry it will go down (you! spoiler!)
Me: Of cause, it might, but not as far as below 1.0
Doc: Well... anyway ...This is not about entering a Guinness book contest

Doc once told me, that, as far as it comes to numbers, he sees just about anything you might think of. So as far as it is within range... Yet, he is usually very careful about predicting something (like your CD4 will go up this much, etc.). The only exception is at month 6, when VL became (finally) < 50, he ventured " and in 6 months your ratio will be over 1.0" . Which it almost did...

Me: do you know the difference between kinetics and dynamics (in general)?
Doc : No.
Me: Kinetics is when you describe things moving (up and/or down), dynamics is when you can describe AND explain by underlying forces
Doc : ??

In fact pharmacokinectics are dedicated to the determination of the fate of substances administered externally to a living organism, where as pharmacodynamics is the study of a drug's pharmacological effect on the body.

There has been a few attempts to model CD4 and CD8 dynamics, but most models have failed when confronted with patients data. The main reason is that, with almost any simple model, one assumes that some parameters remain constant for a period of time. CD4 expansion (proliferation, increase in number by cell division) is increased when a MCH class II must be controlled, and so will CD8 proliferation. These 2 expansions occur in parallel, but their decay follow their own laws (which are different). MCH class II 'attacks' may occurs at a rate/frequency higher than the follow up blood draws.

Then we went on to the physical exam. He was so close to me... While taking my BP, my arm was resting on something soft and comforting that we usually refer to 'hard'
He was wonderful, I was so pathetic, we were wonderful

Cheers!   Eric     
« Last Edit: July 05, 2013, 04:45:50 PM by eric48 »
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Offline eric48

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Hi,

need more on  CD4/CD8 ? go to:
http://www.natap.org/2013/IAS/IAS_48.htm
Lower Peak Viral Load, Higher CD4/CD8 Ratio Linked to Low PBMC Reservoir

Yet we need mathematical model of CD4 dynamics...
It is needed to explain why a Pharma-cure is not impossible and why it has not been (and could not) fully demonstrated yet.

Our models (pending publication) now has a nickname:
Single Compression Quadratic Decay of Infected CD4s and Recovery of Uninfected CD4s (in short the SCQD model)

I will spare the reader the resolution of quadratic differential equations and, for the mathematically obsessed, in the interim, you can read this in detail, if you feel frustrated (good luck with it...)

http://www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1002971

One of the lowdown of our model is that a prerequisite is that NO MCH-Class-II infection should interfere during the period of data collection. Should this happen, and it will happen, then we have to wait for the next favorable period of low immunologic activity.

This is due to the fact that any MCH-Class-II infection will trigger an unmeasurable expansion of CD4s, therefore skewing the decay of the infected cells pool by replenishing it to an unknown level.

Typical infection to trigger a immunologic response involving CD4s are: Influenza, CMV shedding, and, in other words and in the order of appearance in the screen, sorry..., clinical development of late stage AIDS..., all the AIDS-defining opportunistic infections.

Only immunocompetent patient's data can be used and ideally in a non-flu period and hopefully no CMV reactivation period.

While these are very limiting criteria of inclusion for patient's data, I have enjoyed at least 3 extended period of time where those conditions where met (being CMV neg. did help, the flu or flu vaccine, did not...) and therefore 3 calculated points of uninfected CD4 cell pool could be obtained. (please kindly bear in mind that the patient also have to get blood draws at a higher frequency than that covered by health insurance, at his own expense...)

The 3 points are:
at month : the uninfected cell pool is:
   
3   :       145
8   :      383
29 :      669

Next post, I'll put everything on graphs for easier understanding

Most likely an outlier , but still...July 16 blood drawn on a late hot afternoon...
CD4: 1400  CD4 % : 51 ; CD8 : 577  CD8 % : 21
CD4/CD8 ratio: 2.43

Makes me feel good ! Enjoy!

Eric
« Last Edit: July 19, 2013, 04:54:07 PM by eric48 »
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Offline friskyguy

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very insightful article.......thanks eric for sharing.

Hit this disease hard and early to get below 1 viral load on meds and keep your CD4/CD8 ratio high so can keep the infected viral reservoirs low......to have your body in a better place (low reservoirs) to take advantage of a cure when it arrives.

Congrats on your awesome blood results too! Really great!
Sero converted Sept '10 / Confirmed + Dec '10
Jan '11, VL 9,500 / CD4 482 (32%)
Feb '11, VL 5,800 / CD4 680 (37%)
start Atripla
Mch '11, VL UD / CD4 700 (42%)
Jun  '11, VL UD / CD4 750 (43%)
swap to Kivexa and Efav. due to osteopenia diag. (DEXA) / kidney issues ( decline in eGFR to 77 )
start supplements - Vit D3 / Omega 3 / multivitamin / mini aspirin
Dec '11,  VL UD <20 /  CD4 670 (49%)  / CD4:CD8 = 1.4
all labs now within normal ranges
Mch '12,  VL UD / CD4 600 (51%)
Sep '12,  VL UD / CD4 810 (51%)
Mch '13   VL UD / CD4 965 (56%)
Sep '13   VL UD / CD4 (not taken)
Dec '13   VL UD / CD4 901 (35%) / CD4:CD8 = 1.1  /  eGFR > 100

Offline J.R.E.

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 8)

Congratulations Eric on those fantastic numbers.  I may not post often, but I do keep up with this thread !   ;)

I have some labs coming up on August 9th. The last set of numbers took about a 200 point drop in CD4, and some discussion came up, as to a possible switch in regimens. I am still on the 2 separate doses a day of Viramune, and one Epzicom. Was started on an additional dose of 10mg of Lisinopril. This was in addition to the 25mg dose of Hydrochlorothiazide, for blood pressure.

But, I am not going to rush anything, we"ll see how those results come up after the 9th.

Otherwise, All is well!

Take care of yourself !---Ray
Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline eric48

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Hi Ray,

There is not a day where I do not think of you... Here, we are working hard here to find reservoir reducing molecules that help people move to full recovery... I will publish what I am allowed to, here, but this is not always easy (for legal reasons)

We hope to establish a new biotec company soon to finance a clinical trial. It is a lot of stress, trying to find a solution to this hurdle, but, the people I am working with are very enthusiastic. It is inspiring.

Still, I do remember your words every time I am rushing to something: one step at a time. Unless resistance occurs, I would never change my current regimen for anything else.

Like you I am on statin. The statin you are using (if my memory is correct) is not much used here any longer since there are some studies that have proven rovustatin to be superior to others.

I can assure you, we are leaving no stone unturned to try to find new keys.

Good to know you are doing fine and be sure I am with you

Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline J.R.E.

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There is not a day where I do not think of you... Here, we are working hard here to find reservoir reducing molecules that help people move to full recovery... I will publish what I am allowed to, here, but this is not always easy (for legal reasons)

We hope to establish a new biotec company soon to finance a clinical trial. It is a lot of stress, trying to find a solution to this hurdle, but, the people I am working with are very enthusiastic. It is inspiring.




Thanks Eric,...

As always, will be looking forward to your updates when available !


Take care--Ray  8)
Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline eric48

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you can't understand dynamics in continuous media if you don't understand differential equations!

Blood is a continuous media (a liquid moved by a pump) and all experimental work that has been done and have thus far concluded that HAART is a lifetime treatment (Faucy in 99, Siliciano 2003, SMART study 2006) all share the same underlying hypothesis. That the infected CD4 pool decreases logarithmically, in the same way that VL decreases. In the same fashion that radioelements have a logarithmic decay (measured by the so called half life), we speak of CD4 half lives.

The concept of logarithmic decay (or half live) relies on the predicate that the probability for a radioactive element atom to lose its 'radioactivity' in the course of time is a constant, independent from time. In otherwords a radioelement decay event is a no-memory phenomena.

If the piece of radioactive material you are studying shows persistence, then, it is because some of its elements have a long, long half life (or low probability to die, if you prefer)

This would be very true if the only means of viral persistence was through virions entry alone. Yet there are many type of viral material persistence:

A- some CD4 are new borns (in the thymus or bonemarrow) and a few stems cells (mother cells) may be infected (pretty much like vertically infected babies)
B- some viral material will be transferred by virions entry
C- some viral material will be transferred by cell-to-cell bridge (A. Segal 2012)
D- under homeostatic stabilization, or infection attack, HIV infected CD4s (as well as uninfected CD4s) clone themselves thousands or millions of times, hence refuelling the tank.

A - is memory phenomena (as long as the stems cells maintain memory)
B - is a no-memory event, governed by the number of virions
C - is a no-memory, governed by the number of infected CD4 (and the physical proximity
D - is a memory effect: a past event (proliferation) drives the persistence dynamics: our SCQD model takes this into account

as promised our model results go graphic



Blue dots are uninfected CD4s (as per our SCQD model)
Red ones are short lived CD4s that compensate the shortage in uninfected cell
(they are not important at this point and very theoretical concept need for model, hence, I called them 'virtual')

Next post, we will validate the model...graphically

Enjoy ! Eric
« Last Edit: July 30, 2013, 07:40:12 PM by eric48 »
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Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #132 on: August 04, 2013, 12:12:19 PM »
Our model's purpose is to find when the Infected CD4 population goes extinct. Extinction of that species is not exactly eradication. Eradication is when we are sure there is none left and meds can be interrupted. Extinction is more to find when the virus is so low that there is no way it can, by its sole actions, be of any harm. Extinction comes before eradication. As per Pr Siliciano, non-eradication is due to latency of time-isolated, spore-like, quasi-immortal infected CD4 cell. This cannot be modeled by CD4 dynamics. But the almost-zero point of extinction can.

Our models yielded only 3 data points:
at month X there are Y uninfected cells and Z (uninfected+homeostatic compensation)
3,0   145   1127
7,5   383   876
28,2   669   734

Model validation
****************
Be be satisfying the model should be self consistent (not show obvious errors), satisfactory confronted to actual lab test results, give the extinction point and we should then find a way to prove that the extinction point is achieved. Finally, it should be predictive.

Self consistent:
****************
Using Excel, we plot our points and add a default logarithmic trend line.
For both sets, the R2 is very close to 1.0 (0.997 and 0.93, respectively).
on the drawing below I also show a singular point labelled A.



This shows that there is a lag time before uninfected cell starts to appear. They start to appear ca. 1 month after meds initiation, which is very satisfactory and quite convincing. If the trend had hit the Y axis, that would have meant that there was a population on uninfected cells and, with my initial VL of 50K, I do not think this could be possible. If the virus free cells had started to appear quite many months after meds initiation, this would have been inconsistent with my clinical history

Most population growth, such as bacteria in a Petri dish, do exhibit a tiny lag time. So the existence of the tiny lag time is a good point.

An other point of interest is point G (as in Graal, or Goal) this is when homeostatic replication and virion based infection has ceased. It is satisfactory that this point is not way too close to meds initiation. and good to know that it exists! The system is converging.

BTW, I am convinced that in rare patients, the system is not converging; the 2 lines never cross.

More over, the uninfected cell pool is not taking an exponentially explosing shape, so that we are not ending with a million CD4/mL ;-)

confronted to actual lab test results:



Here again the picture is quite satisfactory: all data points are included within the 2 envelopes of our model: CD4 reading are never less than the modelized uninfected cells and never more than uninfected + infected (red line). Blue line cells have a 'normal' half life, whereas red line is a mix or 'normal' half live and 'shortened' half life (due to the infection)

Interestingly enough, the green line is showing a typical damped oscillation pattern.
A good example of a damped oscillation pattern bordered with 2 envelopes is shown here:
https://upload.wikimedia.org/wikipedia/commons/2/2b/Damped_spring.gif
and
http://www.hasdeu.bz.edu.ro/softuri/fizica/mariana/Mecanica/Vibrations+Waves/damped/images/light_damping1.gif

So we are quite happy for today !

Next post, we will refine the trend line, using a better fit pattern that the basic log pattern that Bill Gates offers and plot the 'true' infected cell population: the one that we want to go extinct

Stay tuned, Eric
« Last Edit: August 04, 2013, 12:16:43 PM by eric48 »
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Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #133 on: August 13, 2013, 06:12:57 PM »
Hi,
I am preparing a series of 3 more graphic posts:

1-a- revisit log and sine trending
1-b- estimation of infected cell pool (finally...)

2-a- changing scale to log base scale (stunning graphic effect)
2-b- enter into and through point G with 3D hyperspace motion (very geeky)

3-a- validating our  model with predicting and proving what happens past point G
3-b- the aesthetic beauty of the big SCQD picture

A recommended (easy) reading can be found here (note: go all the way through the presentation until last page - 52)
www.ihlpress.com/pdf%20files/persistence09_presentations/03_Chomont.pdf
which tiny is: http://tinyurl.com/lr2dqlq

revisit log and sine trending
*********************
For easier understanding, I have used Excel default Log trending.
In fact, Log trending is satisfactory at first glance, but Log is an ever increasing function and after a few year you'd find yourself with thousands of 'healthy' CD4s per mL
Therefore we have to change trending to one that is asymptotic.
The following work great for both the blue and red envelopes

Uninfected (blue) = alpha x (1-exp(gamma x time)) + beta
with time expressed in months we have:
alpha = 803.91 ; beta = -113.39 ; gamma = -0.12855
same with the red upper envelope:
alpha = -781.98 ; beta = 1514.68 ; gamma = -0.22700

This additional accuracy seem ludicrous, but, will turn very useful

I kind of implied that CD4 fluctuations are a sine function. Look at the curvature: it is not! Of course, it may help understand this key point: CD4 count go up and down, but NOT erratically: there are driving forces to make it go up and driving forces to make is go down
For the sake of accuracy, let's just forget the sine model, since this is a succession of exponential and quadratic curves
(Quiz for the chemical mind, just a hint: this is a mirror pattern to a Maxwell-Boltzman equation. Have fun!)

1-b- estimation of infected cell pool
****************************
Easy: infected cell pool = CD4 count minus the Uninfected (blue envelope)
and there you go, with some minor changes(*)



(*) changes:
- replaced the SCQD data points by their all new exponential fit for clarity
- changed color of upper envelope to orange so that red is free for infected
- introduced months where VL became <50 and <20
- Unchanged : point A and G

to better understand infection maintenance through proliferation (cell cloning):
www.youtube.com/watch?v=7mZ8Yu5pT6I

Quiz:
******
200 Infected CD4 while VL < 20 !? Possible? Yes or No ?, and explain why...

Follow this thread on twitter (New !!) :
******************************
@HIVPharmaCure

Stay Tuned! Eric
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Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #134 on: September 01, 2013, 06:10:27 PM »
Latest from Siliciano's (free & revolutionnary) sheds new light on PIs:
Multi-step inhibition explains PI pharmacodynamics & resistance
http://www.ncbi.nlm.nih.gov/pubmed/23979165

Then, a good reminder of anatomic compartments and their consequences:
Tissue-specific HIV-1 infection: why it matters
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741055/

The Viramune Paradox unveiled earlier (higher initiation risk, very good long term results), certainly lies on meds ability to diffuse in all anatomic compartments.
Makes life easier: no need to modelize anatomic compartments.

Why these models and why share here?
- SCQD was originally designed to support a proof of concept for a new class of meds (thus, grants, funding and patenting...)
- Share because my numbers & graphs have little interference from 'noise' such as CMV, HVC, thus easier to visualize
- Graphic perspective may help those uncomfortable w/ V&K or meds
- Finally... This is FUN !

Need a refresher on nonlinear modeling?
http://tinyurl.com/nyybskk

compartments ?? see page 78. More on Compartments? see:
http://tinyurl.com/p2cmme7

All models are wrong but some are useful...

And why not.. predictive... while we are at it.
Forecast dated 2013-08-15 for upcoming labs:
2013-09-15 : CD4/CD8 = 2.44 +/- 0.15
2013-11-15 : CD4/CD8 = 2.60 +/- 0.15
Most likely estimate for longer term:
CD4%: 55 CD8%: 16. Wait & see... & remain modest.

Differing from empirical models, SCQD is a mechanistic model: we suggest a mechanism, write (differential) equations, solve, then find unknowns by best fit methods to get our initial data grid. (blue and red squares)

2-a- changing X-axis (Months) to log base scale
It is cool to graph in semi-log. Easier to read... as the human eye evolved to detect edges, lines, not rectangular hyperbolas or exponentials !
Dress code in Semi-log:
- horizontal line (CD4=700) stays horizontal: ---
- a log function gives a straight line with an angle: \
- exponentials give broken lines: \_



Changes
- individual data points removed for clarity
- dashed lines are either data, model or result lines
- solid lines are their Log / Exp / Linear fits (see dress code)
- introduced point E for Extinction
Soon we will include CD8s and past point G data !

Of interest
A- CD4 lab test (green dashed) results average (green solid) is like an arrow entering the funnel-like envelopes. This is why we needed this upper envelope, as it demonstrates the funnel nature of convergence (hence extinction)
B- We easily see: CD4 lab test show an remarkably stable limit cycles, dampened in amplitude with the time to complete a cycle going longer and longer (remember, time axis is a log scale!)

Quiz: what set of differential equations give this type of limit cycle ?

Stay tuned : @HIVPharmaCure       Eric
« Last Edit: September 01, 2013, 06:18:21 PM by eric48 »
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Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #135 on: September 14, 2013, 06:19:39 PM »
Like all good Darwinians, we look toward theory to guide us through the plethora of facts

recommended readings

Chomont's group produce real good stuff. Had to read several times to realize how groundbreaking this might be...
Programmed Death-1 Is a Marker for Abnormal Distribution ...
http://www.ncbi.nlm.nih.gov/pubmed/23918986

The following is very obscure, BUT, in someway, it resembles the mathematical model underlying those graphs I am showing here. Just scroll down past the equations (*) and go right to the graphs p. 23-26.Don't they look pretty much like those on my posts above ?

TWO-DIMENSIONAL STABILITY ANALYSIS IN A HIV MODEL...
http://arxiv.org/pdf/1211.0136v1.pdf
(*): I prefer graphing: it is more fun

Let's include CD8 to our standard (linear) time scale plot



changes
- Added CD8s (plain purple)
- Added CD8 trending, simply the default MS Exp trending,
- the trend (fit) is in dashed purple

And then we go SemiLog, so the CD8 exponential trend will dress as a \__
and we will remove the data plots, keeping just the LOG/Linear/EXP fits



changes:
- beware this is SemiLog time axis
- Data : dashed, fits : plain

Aren't this immuno-dynamics (straight) lines amazing ? (remember in this dress code a straight line can hide either of LOG/Linear/EXP)

about Quiz and Twitter: the quiz hints will appear on the twitter line feed. So regular followers get a bonus primer
TinyUrLs are to be created with direct pointer to key 'chapter' headers in this thread (for easier navigation and reference), then to individual 'main' post later on

Quiz: Which real world object combines 3 movements : 2 wavelike sigmoids and one Exponential ?

I can assure you this is a real real COOL artifact. Easy and Fun to display at a gang bang party (oups!) Kid's Museum

Stay tuned : @HIVPharmaCure   Cheers ! Eric
As of 2013-09-13 : CD4: 1130 CD4%: 39 CD8: 811 CD8%: 28
pointer : http://tinyurl.com/HIVPharmaCure-12
« Last Edit: September 14, 2013, 06:23:26 PM by eric48 »
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Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #136 on: September 27, 2013, 05:55:11 PM »
all well-mixed populations resemble one another, but every structured population is structured in its own way

recommended readings

Incredibly concise, incredibility rich, by very productive A.S. Perelson:
MODELLING VIRAL AND IMMUNE SYSTEM DYNAMICS
http://tinyurl.com/kw2wgqo

Answers lots of questions: why 3 molecules? Why CD8 are so important in controlling the dynamics? Why is modelling so important, etc.

We will use data found in this one, not free, but the supplemental table is
Effect of CMV-induced immune response, ...  ANRS CO3 cohort
http://tinyurl.com/oowe8rn

Why we need a good understanding of Pharmacodynamics? Well... If we want a PharmaCure, or understand the Viramune Paradox, or what to expect once achieved extinction/eradication, or how we prove it, how we reduce time-to-market, etc.

Yet, we need a pause in graphing as I am short of post-G data (takes 1 year to get 6 points... and I missed 2 labs, so ...)
So why don't we play with this funny CD4/CD8 ratio in the interim?
 
CD4/CD8 ratio is of interest because it is the only surrogate marker for reservoir depletion that you and I can easily have access to. I had 2 labs with Proviral DNA (back in 2012) and still working on these research guys to give them to me...
It is also a component to multiple T-cell marker recovery (MTMR), defined as CD4+ T cells >500/mm(3) plus %CD4 T cells >29% plus CD4+/CD8+ T-cell ratio >1.

Because it is a composite parameter, it is hard to master. But let's start with this: in the uninfected population its range is 1 to 4. Not a 'normal' Gaussian distribution, but a skewed, Log-normal distribution, like:
http://tinyurl.com/k7re5wf

It is 'centered' on 1.7 (and not 2.5, as you might expect)
This one below provides a slightly lower range, but, here again, the mean is not at the center, the distribution is slightly skewed
http://tinyurl.com/qy54ngd

Do people who have normalized their ratio, have a normal ratio ?

???

Say, one Hiver under meds has a ratio of 1.2: ratio is back to 'normal'. But, if ALL Hivers, with 'normal' ratio, have a ratio of 1.2, then this population, as a group, is not 'normal'.

Quite fortunately, it appears to be normal. In the absence of table data (infected/normalized and uninfected), we can only compare distribution mode and skewness. If they are similar, then the distribution very likely are

Data for Hivers from Chomont (source: nm.1972-S1.pdf)
among 33 UD Hivers, had CD4/CD8 >1 : 38 %,
among these 38%, : median ratio : 1.66, average 1.7
had a ratio > 1.5 : 61% and a ratio > 2 : 15 % (distribution is skewed)

Data for Hivers from ANRS CO3 cohort
among 200 UD Hivers , had CD4/CD8 >1 : 30 %,
among these 30 % , had a ratio of >1.5 : 43% (thus median slightly less than 1.5) and a ratio > 2 : 20% (distribution is skewed)
(note: in this cohort % of Hivers on statins = 20% ...)

Uninfected population: Skewed distribution, range 1-4, median: 1.5 to 1.7 (depending from source, see http://tinyurl.com/qgyxd5r)

So indeed, Hivers who have normalized their ratio, have a normal ratio

Viramune paradox: 33% of viramune users achieve CD4/CD8 >1, so not superior to either cohort, so CD4/CD8 tells us nothing here.

Beware: CD4/CD8 can flicker, especially around 1. If yours does, then use cautiously. Rule of thumb: Ratio << 1 : usually stable, ratio >> 1 : varies a lot with time, but remains > 1 ; around 1 : flickers between <1 and >1

Quiz:  No obvious relationship ration vs reservoir (in the >1 group, nor in the <1 group): Why ?

Next post will be FUN: non-inferiority of a random generator vs Lab test !

Stay tuned : @HIVPharmaCure       Cheers ! Eric
pointer : http://tinyurl.com/HIVPharmaCure-13
« Last Edit: September 27, 2013, 06:03:41 PM by eric48 »
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline J.R.E.

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #137 on: September 27, 2013, 06:21:09 PM »
Hey Eric,...

Per my last PM, ... It's been since June 2012, that a CD 3, CD8 percentage has been shown in my results: ( From 6/2012)

CELLS.CD3+CD4+    487 Low    cells/uL    490-1740    Details
   CELLS.CD3+CD4+/100 CELLS    15 Low    %    30-61    Details
   CELLS.CD3+CD8+    1669 High    cells/uL    180-1170    Details
   CELLS.CD3+CD8+/100 CELLS    53 High    %    12-42    Details
   
          CELLS.CD4/CELLS.CD8    0.3 Low    ratio    0.86-5.00



Ray
Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline J.R.E.

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #138 on: September 27, 2013, 06:26:47 PM »

This was from December 2011 :

CELLS.CD3    comment    /uL    688-1955    Details
   CELLS.CD4    505    cells/uL    490-1740    Details
   CELLS.CD4/100 CELLS    14 Low    %    30-61    Details
   CELLS.CD4/CELLS.CD8    0.2 Low    ratio    0.86-5.00    Details
   CELLS.CD8    2022 High    cells/uL    180-1170    Details
Current Meds ; Viramune, Epzicom, 40mg of simvastatin, 12.5mg of Hydrochlorothiazide.
Metoprolol tartrate 25mg



http://forums.poz.com/index.php?topic=40802.0

http://forums.poz.com/index.php?topic=45159.0

http://forums.poz.com/index.php?topic=39722.msg495621;topicseen#msg495621

http://forums.poz.com/index.php?topic=46806.0

http://forums.poz.com/index.php?topic=39414.msg491701#msg491701


 In October of 2003, My t-cell count was 16, Viral load was over 500,000, Percentage at that time was 5%. I started my first  HAART regimen  on October 24th,03.

 As of 8/2514,  t-cells are at 402, Viral load <40

 Current % is at 11%

  
 62 years young.

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #139 on: October 12, 2013, 04:54:10 PM »
Thanks Ray, this will turn very usefull and gives us 2 complete readings (reconstructed data: in DEC 2011: CD8% =56%)

Cartographers of yore would have inscribed the warning “there be monsters here”. In the uncharted realms of a HIV Pharmaceutical Cure adventure : monsters be here indeed!

So let's have FUN



recommended readings
WHEN ZOMBIES ATTACK!: MATHEMATICAL MODELLING OF AN OUTBREAK OF ZOMBIE INFECTION
(Munz et al. 2009) available on one of the authors' own page at:
http://tinyurl.com/2vrajmf

This original paper got a lot of attention; but, this one may be easier to read:

Mathematical Modeling of a Zombie Outbreak, by Jean Marie Linhart
http://tinyurl.com/mlh34mv

Pr Siliciano's original set of equation (2003) is all about Target cells and Infected cells (within-patient infection). In population and adaptive dynamics, the targets are named Susceptibles, Infected: Infected (aka Zombies), and... Cured: Removed, Recovered or Imunized-Recovered.(aka SIR, Predator-Prey model and here SZR)

These are autonomous differential equations... Seemingly simple, they have no analytic solution, and can only be approximated numerically

When making some assumptions, it is possible to solve limit equations by calculus. This is a cornerstone to Siliciano's work and to the Latency Theory. Yet, some of the assumptions, dating 2003, may have to be revisited

In Zombies papers, you may easily go past the equations. Stories, descriptions and boxed interaction blocs (see p. 19, 26, 32) are more interesting! Enjoy!

Playing with this funny CD4/CD8 ratio with a random generator

somehow, I felt an urge to play with my ... random generator, testing robustness.
The one that amused me most is to generate CD3% (CD3% be herefrom considered as CD3% = CD4% +CD8%), between its observed boundaries 65% to 75%

Then use the measured CD4% to calculate the CD4/CD8 ratio as CD4%/(CD3%-CD4%) and plot over the measured CD4/CD8 ratio.

And same the other way around using measured CD8% and random CD3%.

There you go

and


Quiz: randomized values are close to measured values. Why ?

Next post: all roads lead to Rome and CD4/CD8 to 1 !

Stay tuned : @HIVPharmaCure        Cheers ! Eric
pointer : http://tinyurl.com/HIVPharmaCure-14
« Last Edit: October 12, 2013, 04:58:09 PM by eric48 »
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #140 on: November 02, 2013, 06:45:32 PM »
Viruses are obligate parasites of autonomously replicating organisms...
(which lymphocytes are...)

Thanks for the encouraging PMs... I'll answer them and also provide further findings on NVP and ABC

recommended readings (hope you have enjoyed the Zombies!)

Not free, hard copy only:
Adaptive Dynamics of infectious diseases (U. Dieckmann 2002)

At page 183: The virus seeks to derive the maximum benefits from the cell's replicative machinery at the least cost to itself

Not free, PDF exists:
Handbook of regression and modeling (applications for the clinical and Pharmaceutical industries) by Daryl Paulson 2006
Not my favorite, but has a lot of self learning tables, examples, figures and is ubiquitous in clinical labs. Lowdown: mostly linear regression

very graphical explanation of derivation p. 28 fig 2.5; (use amazon's look inside with search words: steam exposure)

Those not understanding the basics of triphasic cell decay (hence VL decay), see fig 3.5 (scroll down on amazon's look inside). The graph gives a good approx. idea

Let's do derivation as per Delta(R)/Delta(T) = R(t) - R(t-1) / (t) - (t-1), as we have a fairly frequent sampling, and plot dR / dT as a function of R (R defined as CD4/CD8 ratio) and plot vs R (for ease of use I'll use, abusively, d in place of Delta). We can then do a convincing nonlinear, exponential, regression (not covered by Paulson)


(note: this is done on MY specific labs, so don't over interpret)
As we can see, when R < 1 the speed (dR/dt) is >0 : R moves up towards 1
When R=1 , the speed is 0 : R stays at 1
When R > 1 , speed is < 0 : R moves back towards 1

So my doc, who made predictions only twice (at month 6 to predict that R will 'normalize' to 1, and when R was 1.9, saying it will go down) did this at very limited risk. He who sees many patients, has 'visually' integrated this basic rule that raises his credibility at minimal statistical cost, as lab tests tends to make him right. In this perspective, then, 1 is an attractor of R; R should converge to 1 and stay around there: this is statistically correct but dynamically wrong

Wrong ? What is wrong ? How do we know it is wrong ? 1 is (interestingly) a magic, pivotal, number for R (being at least the rounded lower value for 'normal' range), but is NOT a universal attractor

Quiz: 1 is NOT a universal attractor for R... Prove it, solve it !

Next post: CD4/CD8 dynamic mystery solved !

Stay tuned : @HIVPharmaCure (pls RT)       Cheers ! Eric
pointer: http://tinyurl.com/HIVPharmaCure-15 (please do not highjack, thanks!)
« Last Edit: November 02, 2013, 07:13:26 PM by eric48 »
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #141 on: November 30, 2013, 06:08:24 PM »
It's a magical world, Hobbes, ol’ buddy... Let's go exploring!

I did not publish my latest forecast (got my fingers burnt last time); I should have... The labs results are right on.
As of Nov. 15 2013: CD4: 983 CD4%: 38 CD8%: 27  ratio: 1.4 VL <20

recommended readings


If you are on V&K and think of ridding of Kivexa (aka Epzicom):
Nevirapine-raltegravir combination, a NRTI and PI/r sparing regimen...
http://www.ncbi.nlm.nih.gov/pubmed/24145365

And, on the other hand, if you would like kiss good bye to Viramune:
Dolutegravir plus abacavir-lamivudine...
http://www.ncbi.nlm.nih.gov/pubmed/24195548

Just looking at the graph posted here: http://tinyurl.com/nw65oxq
we know that 1 is not an attractor for CD4/CD8 ratio: there are 3 subgroups
clustered in 2 groups: those with ratio > 1, who cluster around 1.4 - 1.5 ; we did
the maths here: http://tinyurl.com/jwcgptj

For those with ratio < 1, we use Chomont's data and find that they cluster at 0.68
So, statistically there are (at least) 2 statistically stable attractors: 0.7 and 1.4.
We will see later one that there may be a transient attractor at 1.0 and may be a stable attractor at 2.8, but we are not yet there

The problem with R (aka CD4/CD8 ratio) lies in its composite nature. If you own
stocks labelled in a foreign currency, your portfolio may go up because the stock go up OR that foreign currency goes up and vice versa. And when CD4% goes up
significantly, then CD8% is likely a go down at least a bit...This makes R more volatile than the underlying trend is.
To correct for this we introduce a mathematically more rugged animal: Ropt, optimized ratio, the calculation of which goes beyond the spirit of this thread. The
algorithm is not that complex, but, I assume the reader does not really bother. Any
signal processing minded person knows the trick. So it is not so much what Ropt is
that matters, but rather that it is a better toy to play with.

Let's plot R and Ropt. As you can see below they are not very different, similar
trends, except that Ropt is, thus far, more stable



Next post: Exploring a new territory with Ropt derivation: Ropt goes to the Yukon !

Stay tuned : @HIVPharmaCure (pls RT)       Cheers ! Eric
pointer : http://tinyurl.com/HIVPharmaCure-16 (please do not copy, do not highjack, thanks!)
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #142 on: December 13, 2013, 05:20:08 PM »
Things are never quite as scary when you've got a best friend.

recommended readings
CD4 and CD8 T Cell ... Roles of Homeostasis (Marta Catalfamo 2011)
http://m.jimmunol.org/content/186/4/2106.full

While there is little on CD4 and CD8 dynamics, some recent articles are highlighting the driving forces underneath CD4 and CD8 population dynamics. To make it short, the underlying forces are independent in trend and linked in their maximum (aka carrying capacity): CD4 have an autonomous, self fueled proliferation pattern where CD4 growth is driven by ... CD4s themselves. And CD8 have a proliferation pattern driven by signs of infections (such as free RNA, aka VL and signaling infected cells)

Graph on my previous post is showing one thing of interest: we are now 3 and 1/2 years into a treatment started quite early and we see, on the ratio trend, that the immune restoration is still in progress. This graph is better than a thousand words to show the importance of time in recovery. The median treatment time in the SMART study was 3.5 y... Why would anyone be hopefull that treatment interruption can be successful if the recovery is still in progress ?

Earlier, we had graphed the derivative of R: a nice but not over exciting exercise. 
Today, I am posting a graph that I think is quite unique.
Let's graph the derivative of R-opt (aka dRopt/dt, or speed, if you want) vs Ropt.

I had to move, very marginally, the X coordinates of 3 data points, to improve clarity. Even marginally edited for educational purposes, this graph is much more exciting. There you go:   



Keeping in mind the diagram I posted here: http://tinyurl.com/HIVPharmaCure-10

I hope you are guessing where I am getting at ;-)

Next post: Ropt potential well and recovery progress !

Stay tuned : @HIVPharmaCure (pls RT)       Cheers ! Eric
pointer : http://tinyurl.com/HIVPharmaCure-17 (please do not copy, do not highjack, thanks!)
« Last Edit: December 13, 2013, 05:24:43 PM by eric48 »
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #143 on: December 22, 2013, 05:12:47 PM »
Most natural systems evolve according to multistep processes. We refer to these dynamics as punctuated evolution

Nonequilibrium systems evolve in time, not according to a smooth or gradual fashion, but by going through periods of stagnation interrupted by fast changes.

I have finally found ways to graph the multistep changes in a very convincing manner, so next posts are going to be exiting!

I am not losing focus: show the 'unfortunate' users of 'low cost' NVP that its very simple structure makes it a very good ally in reservoir lowering strategies.

Yet, non-progress may involve steps forwards and steps backwards, and, I'd like to make sure that progress is sustained.
2013 started with mixed results with ratio flickering around 1. For 6 months now we have repeatedly had a ratio > 1.4

So we can look forward to 2014

In next posts, I'll explain the significance of the above graph, move to another very exiting graph, review my latest tricks against 'brain fog', anxiety and sleep issues and finally explore if our (earlier defined) point G is an extinction point of sorts and see when we can hope to reach a point where we can experiment further.

I remain convinced that remission is possible. It is just a matter of time until we find the keys to the challenging hurdle

This is Xmas time, so no maths for this post. Feel free to throw a marble (or glass sphere) in your cereal bowl, watch the movement, speed, etc. in case you have forgotten about potential wells. We may need that...

I did not like 2013 much. But I have enjoyed the 1400 CD4, and the PMs, and the graphs, and time spent with you guys.

So, I wish you all a Merry Christmas

Looking forward to the Holidays and challenging discussions in 2014

Next post: Ropt potential well and recovery progress !

Stay tuned : @HIVPharmaCure (pls RT)       Cheers ! Eric
pointer : tinyurl.com/HIVPharmaCure-18 (please do not copy, do not highjack, thanks!)
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #144 on: January 08, 2014, 09:05:25 AM »
How could they see anything but the shadows if they were never allowed to move their heads -Plato

recommended readings
viral load white paper by B. Taiwo
http://tinyurl.com/qzlblor
A very informative review of VL, blips, and clinical management

Characteristics determinants of T-cell phenotype normalization (not free)
http://www.ncbi.nlm.nih.gov/pubmed/24304582
The abstract is all we need, but, for further reading go there (free):
http://tinyurl.com/pzrb3fh

T-cell phenotype (TCP) has several definitions and the one, here, is interesting.

We can envision several types of 'cures' (aka HIV cure)
-A- treatments coming from the cancer specialists (graft, radiotherapy)
-B- Bio treatments (Sangamo, therapeutic vaccine, vaccines...)
-C- PharmaCure (FAUCI's concept when he attempted Treatment Interuptions)
-D- Non-portable cures (Visconti...)

A : no thanks; B : Somewhere, sometime, most likely the best, but, not in our reach; D : We can learn from them, but if the prerequisite is that you get meds within a few days of infection, then, as far as I am concerned, it's too late
C (Pharmacure) is slow progression from one status to another until We reach ultimate favorable factors and see if a remission is possible

Thus we need to define these 'status': the left hand side of our cursor is disease, the right side is 'cured' and there are things in between that are step stones towards the cure itself.

TCP as defined in the above article is :
- CD4 T-cell count >532
- T-cell homeostasis (CD3> 65% and < 85%)
- CD4:CD8 ratio >1.2

The T-cell homeostasis is unusual, interesting... This is not something we consider
much. Yet, at baseline, 32% of patients had lost homeostasis. Not everyone recovers this. If you do not know your CD3%, just add CD4% + CD8% and you are about right. So, if you do not have access to CD3% , per se, substitute with (CD4% + CD8%)

Only 2% of patients meet the 3 criterias. Of note, achieving a normal CD4:CD8 ratio was not associated with better clinical outcome.

Interestingly, 99% exhibited ratio dysregulation at baseline... In other words, in that game, we all start in the same line, pretty much like in a video or role game.
Patients initiating meds at CD4 600 have a head start in the CD4 contest, but, not
in the ratio marathon. For me, CD4 T-cell count >532 cells took 3 weeks but CD4:CD8 ratio >1.2 took ... 3 years !

Pretty much as in cross country or cycling, how fast you get to the goal depends on the relief or terrain (aka topography). And recording speed tells you about the map ...
Revealing the underlying terrain ... This is exactly what my latest graph aims at.

Quiz: are you seing the relief in the speed graph ? It's easy

Next post: Ropt potential well explained !

Labs as of 2014-01-02 : CD4: 1091 (37%) CD8:855 (29%) CD4/CD8: 1.3

Happy New Year !

Stay tuned : @HIVPharmaCure (pls RT)       Cheers ! Eric
pointer : http://tinyurl.com/HIVPharmaCure-19 (please do not copy, do not highjack, thanks!)
« Last Edit: January 08, 2014, 09:07:55 AM by eric48 »
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline newt

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #145 on: January 08, 2014, 06:36:51 PM »
Quote
Of note, achieving a normal CD4:CD8 ratio was not associated with better clinical outcome.

Indeed, the salient point

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

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #146 on: January 27, 2014, 05:32:10 AM »
...Establish a predictive model for identifying patients who are most likely to respond to the test treatment under investigation...

Thanks for the comments and PMs, as always ...

recommended readings

Sometimes good to review your basics ...
viranume review (useful for users, an updated version would be appreciated)
http://tinyurl.com/kg5znus

Viramune users read if (voluntary or involuntary) treatment interruption:
http://www.aidsmeds.com/archive/Viramune_1616.shtml
especially the bolded part : In turn, ... drugs

Central Nervous System Complications  (by CPE originator Letendre)
http://www.iasusa.org/sites/default/files/tam/19-4-137.pdf

CPE was the reason I chose V&K

CD4/CD8 ratio is the only patient available signature for a lower reservoir. Until we have something better... We are exploring Pharmacure(s) and lower reservoir appears valuable if you are contemplating treatment simplifications or interruptions. For Viramune users, reducing one molecule does not seem to be a viable option ;-)

If you do not understand or remember the concept of potential well and what follows, do not worry, I have a newer graph ready to go which is much easier to understand. Need be, see : http://tinypic.com/r/x43n8x/5

Once you have the speed profile at first pass, the underlying potential is revealed: the higher speed is at the bottom of the (cereal) bowl and lower to zero speed at the vertical so we just need to flip the curve upside-down. The terrain reveals 3 zones and 2 to 3 attractors: 0.7 ; 1.4 and maybe 1



Well... We are done with this for the time being... We now have a map!

Next post: Ropt shows S-curve efficacy and more !

Stay tuned : @HIVPharmaCure (pls RT)       Cheers ! Eric
pointer : http://tinyurl.com/HIVPharmaCure-20 (please do not copy, do not highjack, thanks!)
2014-01-26: started ANT project
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #147 on: February 17, 2014, 04:33:16 AM »
Models provide a rigorous means of thinking about and describing the immune system and its interactions with viruses and other pathogens

recommended readings

Exciting: downregulating CCR5 expression by famed Dr Gero Hütter
CCR5 as a Natural and Modulated Target for Inhibition of HIV
http://www.mdpi.com/1999-4915/6/1/54/pdf

Fun: completely OFF topic but really weird : Whoonga Whoonga !
Whoonga and the Abuse and Diversion of Antiretrovirals...
http://www.ncbi.nlm.nih.gov/m/pubmed/24370963/

Our entertaining journey through the mathematics of Zombies showed that the set of equations derived from N compartment trafficking (Suceptibles, Infected, Removed ...) is sized (at least) N x N. So the minimum is 9 (which may be reduced to 6 through blunt simplifications), not withstanding additional parameters (degrees of freedom) such as time delays.

When I have time, I'll show a fairly successfull, Zombie-like numerical and graphic dynamics of the immune system.

In any case, the degrees of freedom are too many: we will not have enough data points to estimate them... We sense that there is a set of equations underlying our observations (lab test) but we can't resolve the complexity. There is a turn around:

The logistic equation, advanced by Verhulst, has been the workhorse model for describing the evolution of various social, biological, and economic systems. Resulting in a 4 parameters Logistic curve (aka S curve) for symmetric datasets and extended to 5 Parameters Logistic curve (5PL- S curve) for asymmetric datasets, it has proven at least as good as the complete Mass Action Equations (*) in modelling phenomena showing this common pattern:
1- (slow) start (almost zero speed)
2- increasing speed to a single maximum
3- lowering speed
4- (slow) end (saturation) (almost zero speed)
See: http://en.wikipedia.org/wiki/Logistic_function

(*) Anyway, Lymphocytes being free replicating cells, Mass Conservation rule is violated

We can easily see this pattern in the First part of our speed diagram.
http://tinyurl.com/HIVPharmaCure-10

The S-curve demonstrate the efficacy of an intervention (here the introduction of HAART), such as a Receptor/ligand binding or inhibitors, which we are familiar with. If the intervention is efficient, then, we should find an S-curve that clearly reveals efficacy. BTW, that could be a more discriminant efficacy indicator than non-inferiority clinical trials which require too many patients and would allow to work with smaller cohorts, at a lower cost.

Let's fit Ropt (year 1 of treatment) to 4PL S-Curve in the form of:
Ropt = Bottom +( (top-bottom) / (1 + exp ((V50 -X)/Slope) ) )
Numerical results are (X = time in months)
Bottom = 0.619 ; top= 0.929 ; V50 = 4.537 ; slope = 0.607
(fit quality R2 = 0.996 !)


 
This PharmacoDynamics graph is much easier to read than our speed diagram, isn't it

Next post: S-curve # 2 to show additional efficacy !

Stay tuned : @HIVPharmaCure (pls RT)       Cheers ! Eric
pointer : http://tinyurl.com/HIVPharmaCure-21 (please do not copy, do not highjack, thanks!)
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #148 on: March 18, 2014, 08:13:30 PM »
Every problem is obsessively simple when explained. If you can't explain it simply, you don't understand it well enough.

Thanks for messages and support. Indeed, if you want to keep a post short, it is
condensed and too rich, difficult to digest. I'll try my best... Special thanks to X, St, HfC, ...

For the newer generation

recommended readings

Oddly enough, this very post. Yes... The graph below wasn't ready for
CROI2014 submission deadline. LOL. Well I hope you will appreciate the value of
this graph, which is 100% based on patient accessible data, is the result of higher
frequency blood draws and creative graphing. The data acquitions spans over more than 3 years and have been timely reported here.

We've reached our destination (lower reservoirs): that is not disputable. The
depletion may have been achieved around Jan 2013, but another set of 6 data points have been necessary to complete the curve below. We travelled under favourable winds.

The S curves have one advantage that make them a decisive tool in chemistry,
biochemistry, pharmaceutical design and many other effective sciences. The
likelyhood that data points will align along an S curve by pure chance is virtually
zero. This has to do with the Confidence Intervals (CI) which I have reported on
the graph (black fine lines are at CI 95%). In the sharper increase phase of the S
the confidence intervals are very narrow, so the likelyhood that S showed up by
chance is very very small.

Part A (first potential well) of our graph had lead us to an S-curve in that region, the later part of the same graph (say... C) leads to another S curve... The B area is flat, showing no trend...
Are the S-curve nothing but a mere re-graph of our speed graph with 2 potential
wells. Well... the graphs are not unrelated, but we are not redrawing the same
thing in a different representation space. In Speed curve we have plotted dR/dT
(the speed of R) vs R, here, we are plotting Ropt vs TIME. While R, Ropt, dR/dT are known with some uncertainty, TIME is defined accurately. There is a margin of error in the X AND Y axis of speed on potential well curves. On S curves, the uncertainty is only on the Y axis. 



This second S curve unveils a second kick, that comes well after initiation. The graph is partial as I have isolated the second S-Curve. The delayed efficiency is, in amplitude, similar to the initial efficiency: the ratio is almost doubled each time (it just looks bigger, but it is not)

I hope this makes treatment progress easier to visualize

New Labs: CD4: 1305 44% CD8 771 26% R=1.7 and ... UD ! !

Quiz : In CD4, what means C , D and 4 ?

Next post: the complete double-S curve and where we go from there !

Stay tuned : @HIVPharmaCure (pls RT)       Cheers ! Eric
pointer : http://tinyurl.com/HIVPharmaCure-22 (please do not copy, do not highjack, thanks!)
2014-03-18: started STARFISH project
« Last Edit: March 18, 2014, 08:37:00 PM by eric48 »
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #149 on: April 21, 2014, 08:29:20 AM »
Things that I am preparing:

Viramune

- we now have Viramune / generic Viramune and Viramune XR: which one to choose: I have recently received Generic Viramune, so I'll try it
- Viramune detox
- understanding NVP (and EFV) Pharmacokinetics : how you can benefit from knowing more about your meds
- revised, detailed Viramune stop procedure based on recent analysis from SMART study trial and 'tail covering' trials

Reservoir reduction 

- a combined graph with both S-curves on the same graph
- database driven graphs (*) so that I can update graphs
- exploring Post-G data and explaining treatment punctuations
- CD4 > 1000 : is this a good thing ?
- developping R-opt 2.0

Posting with graphs

Is fun, makes things easier to understand.
GIF or JPEG graphs cannot be maintained as time goes.

(*) Currently looking for a SVG enabled, computation enabled service where I can port the graphs to.

Cheers  Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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With 4 parameters I can fit an elephant. With 5 I can make it wiggle his trunk

recommended reading
Dynamics of Cancer : Incidence, Inheritance, and Evolution by Steven A Frank
http://tinyurl.com/cm8blnc

Dynamics are generally speaking less known to the public. No need to read in detail, just browse thru
This book emphasize the use of speeds (time derivatives) and acceleration, just as we did in previous posts, as a framework for better model validation.

Having a model would be more fun if it were predictive: let's give it a try

Forecast for upcoming blood draw (aka ImmunoForecast)

CD4 % around 49
CD4 > 1100 but less than 1300; estimated at 1100
CD8 % around 23
CD8 estimated at 520
CD4/CD8 around 2.1

Still open:
Quiz : In CD4, what means C , D and 4 ?

« Last Edit: May 06, 2014, 09:24:26 PM by Jeff G »
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline Hellraiser

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Quiz : In CD4, what means C , D and 4 ?

Cluster of Differentiation 4

Offline eric48

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We have not finished. Meds have cured noone (*). And that is the problem

(*) with exception of Viscontis and a handfull of others

Thanks ! Yep ... See:
http://en.wikipedia.org/wiki/CD4

No room on a post like this to explain C and D, but maybe one can easily explain the 4 (in relation to 8)...

Since my previous post included a prediction and blood test was done May 12, I now know the quality of the prediction exceeds my expectations. In order to set expectations right I have published a foreword to put in perspective how a predictive model should be tested and prove its worth.

Here again there is no room here to publish this (too many numbers), so I have published on the Tumblr account. I am new to Tumblr so there is a learning curve. Also I'll wrap this up into graphs , easier to read, but this takes time ...

www.tinyurl.com/HIVPharmaCure-T1

I'll post the graphs here as well.

Visit to Doc:  UD as usual...
He offers Complera, but, no, I want to stay on Viramune. I am starting using generics (Mylan) and I want to report to fellow Viramune users

May 12 started  Boneozard

Quiz : In CD4, what means 4 ?

Stay tuned : @HIVPharmaCure (pls RT)       Cheers ! Eric
pointer : http://tinyurl.com/HIVPharmaCure-24 (please do not copy, do not highjack, thanks!)
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline eric48

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just to add : I have kept this thread active for four years : this is the 4 y. anniversary
Also I'd like to change the quiz question from
Quiz : In CD4, what means 4 ?
to Quiz : In CD8, what means 8 ?  Eric
NVP/ABC/3TC/... UD; CD4 > 1000; CD4/CD8 ~ 2.0   safety stock : 3 months (2013: FOTO= 5d. ON 2d. OFF)

Offline ad2san

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Re: 06/10 Starting Viramune (Nevirapine) + Kivexa (Epzicom = 3TC / abacavir)
« Reply #154 on: September 07, 2014, 05:52:06 AM »
I think the name CD4 and CD8 is because of there shape ?
Feb   2009 CD4 358 VL 2000 16%
May  2009 CD4 305 VL 3069  14% <---- Started TVD+ATZ/r
Jul  2009 CD4 512 VL <50   18%
Jul 2010 CD4 418 VL <50 24%                     
Switched to Kivexa (Epzicom) + Norvir + Reyataz (due to sleep problem)
Aug 2010 CD4 606 VL <50 25%
Jul 2011 CD4 494 UD 23%
Switched to Kivexa (Epzicom) + Viramune XR (due to kidney problems)
January 2012 CD4 564 UD 31%
October 2012 CD4 684 UD 29%
January 2013 CD4 594 UD 26%
Switched to Kivexa (Epzicom) + Isentress due to BIG increase GammaGT
Feb 2013 CD4 699 UD 28%
May 2013 CD4 385 UD 28%
July 2013 CD4 CD4 636 UD 25%
Oct 2013 CD4 588 UD 39%
Aug 2014 CD4 639 UD 25%

 


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