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Author Topic: Discordant virological and immunological responders.  (Read 2241 times)

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Offline JamieD

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  • Posts: 259
Discordant virological and immunological responders.
« on: August 08, 2007, 03:41:38 PM »
I am bring this over from another thread.



Am I the only person who have ever heard of discordant responders? I remember a big long article about this about a year ago. Basically its people who's CD4 cells go up, but do not achieve any or full virogical suppression OR people who achieve adequate virological suppression but do not see their CD4 cells go up.
Since becoming positive I have met some people who are HIV+, and I know of one person who says that he has been undetectable for 2 years (and a few months) and has not seen ANY increase in his CD4 cells. "Not even one" he says. There are the normal fluctuations he says but it always comes back to where it started.

http://jac.oxfordjournals.org/cgi/content/full/58/3/506

This article says that it is reported to happen in 20-30% of people, so I am not quite sure why everyone was so shocked when the person in the other thread said his CD4 cells went up, but his viral load did not go down.

Offline JamieD

  • Member
  • Posts: 259
Re: Discordant virological and immunological responders.
« Reply #1 on: August 08, 2007, 09:08:40 PM »
Is everyone stunned or something? Did I say something wrong?

Offline milker

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Re: Discordant virological and immunological responders.
« Reply #2 on: August 09, 2007, 12:09:11 AM »
I read it, saw the references, and decided that I should do more research on it. So thanks for sharing, I don't have any comment on it yet tho !

Milker.
mid-dec: stupid ass
mid-jan: seroconversion
mid-feb: poz
mar 07: cd4 432 (35%) vl 54000
may 07: cd4 399 (28%) vl 27760
jul 07: cd4 403 (26%) vl 99241
oct 07: cd4 353 (24%) vl 29993
jan 08: cd4 332 (26%) vl 33308
mar 08: cd4 392 (23%) vl 75548
jun 08: cd4 325 (27%) vl 45880
oct 08: cd4 197 (20%) vl 154000 <== aids diagnosis
nov 2 08 start Atripla
nov 30 08: cd4 478 (23%) vl 1880 !!!!!!!!!!!!!!!!!!!!!!!!!!
feb 19 09: cd4 398 (24%) vl 430 getting there!
apr 23 09: cd4 604 (29%) vl 50 woohoo :D :D
jul 30 09: cd4 512 (29%) vl undetectable :D :D
may 27 10: cd4 655 (32%) vl undetectable :D :D

Now accepting applications from blowjob ninjas™

Offline JamieD

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  • Posts: 259
Re: Discordant virological and immunological responders.
« Reply #3 on: August 09, 2007, 12:19:55 AM »
I just don't see why everyone is so shocked at this other person's results. If at the bare minimum only 20% of people experience it, thats still 1 in 5. Surely someone else has had to have heard of it before.

Offline Miss Philicia

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Re: Discordant virological and immunological responders.
« Reply #4 on: August 09, 2007, 12:23:23 AM »
Well personally for a long, long time I qualified as this with the first part "sustained CD4+ cell count rise despite persistent viraemia."

Other than that I've not heard this termed as such, but it's interesting.
"I’ve slept with enough men to know that I’m not gay"

Offline milker

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Re: Discordant virological and immunological responders.
« Reply #5 on: August 09, 2007, 12:26:47 AM »
The studies quoted there say 20-40%, which is extremely high to me. So that's why I didn't react on here, because being that high I should have heard about it before, it would have been discussed a lot, and I don't recall seeing a discussion about this. So that's why I put that on my "todo" list.

Milker.
mid-dec: stupid ass
mid-jan: seroconversion
mid-feb: poz
mar 07: cd4 432 (35%) vl 54000
may 07: cd4 399 (28%) vl 27760
jul 07: cd4 403 (26%) vl 99241
oct 07: cd4 353 (24%) vl 29993
jan 08: cd4 332 (26%) vl 33308
mar 08: cd4 392 (23%) vl 75548
jun 08: cd4 325 (27%) vl 45880
oct 08: cd4 197 (20%) vl 154000 <== aids diagnosis
nov 2 08 start Atripla
nov 30 08: cd4 478 (23%) vl 1880 !!!!!!!!!!!!!!!!!!!!!!!!!!
feb 19 09: cd4 398 (24%) vl 430 getting there!
apr 23 09: cd4 604 (29%) vl 50 woohoo :D :D
jul 30 09: cd4 512 (29%) vl undetectable :D :D
may 27 10: cd4 655 (32%) vl undetectable :D :D

Now accepting applications from blowjob ninjas™

Offline Dachshund

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  • Posts: 5,954
Re: Discordant virological and immunological responders.
« Reply #6 on: August 09, 2007, 05:40:19 AM »
There is limited information on the pathogenesis, risk factors, prognosis and clinical management of discordant immunological and virological responses to antiretroviral therapy, despite its relative frequency. The development of standardized and universally accepted definitions of discordant responses is necessary to allow meaningful comparisons between studies to be made, as well as to help in the design trials of possible therapeutic interventions.


Why would anyone be stunned?

Offline gerry

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  • Joined AM Feb 2003
Re: Discordant virological and immunological responders.
« Reply #7 on: August 11, 2007, 12:46:05 AM »
I don't think you are the only one who has heard of discordant responders.  Clinicians who treat many HIV patients would certainly see a spectrum of responses.  The people were reacting to the other thread not because of your response but because you do not see people on a potent combo such as Atripla have viral loads remain at >100,000 after 8 months of treatment unless they are resistant to most of the component meds in the Atripla.  So assuming proper compliance, the first thing to figure out here is if the lab test results are really as they have been reported.  If they are really correct, then the next thing is to determine the presence of drug resistance by running a genotype resistance test.  It has also been pointed out that the resistance test should have been done or considered sooner rather than later in someone who is on a regimen such as Atripla with viral loads remaining persistently high because it takes only one mutation each to make the virus completely resistant to the efavirenz and lamivudine component of the medication, and a series of mutations may develop against the AZT component which may cause cross-resistance to even the other NRTIs that the person has not even used, therefore limiting future treatment options further.  If you read through the article it says:

"For patients with a sustained CD4+ cell count response, despite persistent viraemia, the goal of therapy should remain the suppression of HIV-1 RNA to levels below 50 copies/mL. A detailed assessment of adherence, drug intolerance and pharmacokinetic issues should be done to rule out modifiable causes. If none is encountered, then modifications in the antiretroviral regimen should be considered, the choice of drugs being dependent upon patient history and resistance testing."

That's what is being recommended by others...

Offline JamieD

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  • Posts: 259
Re: Discordant virological and immunological responders.
« Reply #8 on: August 11, 2007, 01:59:28 PM »
There is no AZT or lamuvidine in Atripla. It consists of tenofovir, efavirenz, and emtriva.

Offline newt

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  • the one and original newt
Re: Discordant virological and immunological responders.
« Reply #9 on: August 12, 2007, 08:37:48 AM »
Correct..

...but Atripla contains emtricitabine which is more or less the same as lamivudine, and unsuppressed viral replication on Atripla is likely to lead to (1) quickly, lamivudine/emtricitabine resistance (2) additional mutations which can  cause cross-resistance to all drugs in the nucleoside class, including AZT and the other nuke component of Atripla, tenofovir.

The key point in Gerry's post for me is that, whatever the reason, high viral load while on Atripla is very likely to lead to serious resistance to both non-nukes and nukes, and needs sorting asap.

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

Offline gerry

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  • Joined AM Feb 2003
Re: Discordant virological and immunological responders.
« Reply #10 on: August 13, 2007, 10:34:06 AM »
Sorry, you're right.  It's efavirenz, FTC, TDF.  This makes it more important to investigate resistance issues if those labs were correct because it takes only 1 mutation each to make the virus resistant to all 3 components (the 103N, 184V and 65R).  Thanks for the correction.

 


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