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Author Topic: Numbers on Virologic Failure  (Read 5734 times)

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Offline oksikoko

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  • Writing the congressman again
Numbers on Virologic Failure
« on: August 24, 2013, 12:52:21 am »
So, I was casually thumbing through a study comparing dolutegravir to raltegravir, like you do on a Friday night, and I came across this line:

"Significantly fewer patients had virological failure with treatment-emergent integrase-inhibitor resistance on dolutegravir (four vs 17 patients; adjusted difference −3·7%, 95% CI −6·1 to −1·2; p=0·003)."

So, out of 354 people on dolutegravir, 4 had virologic failure in a 48-week period, and 17 out of 361 on raltegravir (Isentress) suffered the same.

Is it just me, or doesn't that seem like a lot? I don't personally know anyone that has had this happen, and I even know a few people who only take their pills like aspirin, when they feel sick... Still, no virologic failure.

Have any of you experienced this? Did you know ahead of time or did you only know when the doctor told you.

Sincerely,
Lee, off to find numbers for Stribild...
Code: [Select]
2014-11-14: CD4 Wars Episode II: Return of the Stribild (released in Europe as Stribild II: Werewolf Bitch)
2014-11-06:                ☣ VL (→) 12,627      ☣ CD4 (→) 639
2014-??-??: off treatment  ☣ VL (?)              ☣ CD4 (?)
2013-10-03:                ☣ VL (=) undetectable ☣ CD4 (+) 1105
2013-05-23:                ☣ VL (=) undetectable ☣ CD4 (-) 945
2013-02-25:                ☣ VL (-) undetectable ☣ CD4 (+) 1123
2012-12-16: Enter Stribild
2012-11-20: HIV+           ☣ VL (→) 132,683      ☣ CD4 (→) 920
2012-04-01: HIV-
Dates in this signature file conform to ISO 8601. ;-)

If no one complains, nothing will ever change.

Offline Jeff G

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Re: Numbers on Virologic Failure
« Reply #1 on: August 24, 2013, 01:03:39 am »
The first drug my doctors tried when I wanted off Atripla was Isentress and it didn't work for me at all . I went from undetectable to a viral load of 25,000 in six weeks with complete adherence .
HIV 101 - Basics
HIV 101
You can read more about Transmission and Risks here:
HIV Transmission and Risks
You can read more about Testing here:
HIV Testing
You can read more about Treatment-as-Prevention (TasP) here:
HIV TasP
You can read more about HIV prevention here:
HIV prevention
You can read more about PEP and PrEP here
PEP and PrEP

Offline Ann

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Re: Numbers on Virologic Failure
« Reply #2 on: August 24, 2013, 06:33:57 am »
When I was finally permitted to go on treatment and had the "what combo?" discussion with my doctor, I explained why I went for a PI based combo (once a day, without possible Sustiva issues). I told him it came down to atazanavir or dolutegravir and I decided to go with dolutegravir to avoid the bilirubin issue and also because I know so many (from these forums) who take it with little or no side-effects.

He said I made an excellent choice and not only did he mention the study you're talking about, but he also said it crossed the blood/brain barrier more efficiently than atazanavir.

We then had a side-discussion about how the blood/brain barrier thing might possibly be involved in the virologic failure issue. He's currently doing a study looking at how viral "spill-over" from the brain contributes or causes VL "blips". http://england.ukcrn.org.uk/StudyDetail.aspx?StudyID=10473 Interesting (but speculative) stuff.
Condoms are a girl's best friend

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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 oksikoko

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Re: Numbers on Virologic Failure
« Reply #3 on: August 24, 2013, 11:39:30 am »
The first drug my doctors tried when I wanted off Atripla was Isentress and it didn't work for me at all . I went from undetectable to a viral load of 25,000 in six weeks with complete adherence .

That sucks. :( But you got off the Atripla in the end. :) What combo did you end up on?

He said I made an excellent choice and not only did he mention the study you're talking about, but he also said it crossed the blood/brain barrier more efficiently than atazanavir.

We then had a side-discussion about how the blood/brain barrier thing might possibly be involved in the virologic failure issue. He's currently doing a study looking at how viral "spill-over" from the brain contributes or causes VL "blips". http://england.ukcrn.org.uk/StudyDetail.aspx?StudyID=10473 Interesting (but speculative) stuff.

Fascinating. I'll be following this. My CNS has always been my enemy. It just figures it's collaborating with HIV. Haha.
Code: [Select]
2014-11-14: CD4 Wars Episode II: Return of the Stribild (released in Europe as Stribild II: Werewolf Bitch)
2014-11-06:                ☣ VL (→) 12,627      ☣ CD4 (→) 639
2014-??-??: off treatment  ☣ VL (?)              ☣ CD4 (?)
2013-10-03:                ☣ VL (=) undetectable ☣ CD4 (+) 1105
2013-05-23:                ☣ VL (=) undetectable ☣ CD4 (-) 945
2013-02-25:                ☣ VL (-) undetectable ☣ CD4 (+) 1123
2012-12-16: Enter Stribild
2012-11-20: HIV+           ☣ VL (→) 132,683      ☣ CD4 (→) 920
2012-04-01: HIV-
Dates in this signature file conform to ISO 8601. ;-)

If no one complains, nothing will ever change.

Offline Jeff G

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Re: Numbers on Virologic Failure
« Reply #4 on: August 24, 2013, 02:56:55 pm »
Hi oksikoko . Im on Truvada and Intelence and I haven't had any side effects at all from it but most importantly its doing a good job viral load wise .

I haven't had a cd4 count on this med as of yet so I'm curious as to how that's going to work out . I'm also using about half the insulin since I got off Atripla but not sure if there is a solid connection .       
HIV 101 - Basics
HIV 101
You can read more about Transmission and Risks here:
HIV Transmission and Risks
You can read more about Testing here:
HIV Testing
You can read more about Treatment-as-Prevention (TasP) here:
HIV TasP
You can read more about HIV prevention here:
HIV prevention
You can read more about PEP and PrEP here
PEP and PrEP

Offline eric48

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Re: Numbers on Virologic Failure
« Reply #5 on: August 24, 2013, 04:39:26 pm »
We then had a side-discussion about how the blood/brain barrier thing might possibly be involved in the virologic failure issue.

See (free article):
Tissue-specific HIV-1 infection: why it matters
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741055/

BTW, this the very reason why I went on V&K

anti-retroviral CPE 2010 ranking can be found here:
http://www.natap.org/2011/CROI/croi_139.htm

you will have to scroll down, quite a bit, until you find the relevant table

for example, V&K has a score of 9.

The pb with highly penetrative drugs in the brains, is exactly that they are highly penetrative! your brains are 'medicated'
My doctor - virologist though it would be a good idea and preventive
My expert - neurologist said this was pure BS

BTW, it may be safe to do stop and go with some combos like Atripla, but, certainly not with a combo containing Viramune

oksikoko: do not forget that double blinded clinical trials are designed to eliminate some experimental bias. One of them is people reporting 100% adherence, while, in fact they did not.

depending on combos and definition of virologic failure rates can be from 10 to 20%

You will find this this in table 3 of the following paper
(note: Note: Response rate refers to HIV RNA < 50 copies/mL)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234156/pdf/ceor-3-197.pdf

While it is often said that if you are 95%+ adherent virological success can be secured for many years, there is one study that showed 1% failure rate per year on people otherwise reporting 100% adherence
(If forgot the link, but I think it comes from the va cohort)

Hope this helps

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

Offline leatherman

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Re: Numbers on Virologic Failure
« Reply #6 on: August 24, 2013, 08:50:19 pm »
While it is often said that if you are 95%+ adherent virological success can be secured for many years, there is one study that showed 1% failure rate per year on people otherwise reporting 100% adherence
it's not really "often said" as much as studies have proven.  ;)

and as to that "1% failure rate for people otherwise reporting 100% adherence", was that 100% adherence rate designed into the study or was that simply what patients reported? If it's patient self-reporting then that 1% failure rate hasn't been proven. Although 1% failure rate is pretty damn good when you think probably a decent percentage (10%? more) of those patient self reporting are not telling the truth and not 100% adherent.
leatherman (aka Michael)

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

Offline Ann

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    • Num is sum qui mentiar tibi?
Re: Numbers on Virologic Failure
« Reply #7 on: August 25, 2013, 07:44:00 am »

Fascinating. I'll be following this.


I'm following the study too - because it's interesting, and also because my partner was one of the guinea pigs test subjects.
Condoms are a girl's best friend

Condom and Lube Info  

"...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 wolfthorn

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Re: Numbers on Virologic Failure
« Reply #8 on: August 25, 2013, 09:11:01 pm »
Self-reported 100% adherence is not super reliable.... I was 100% with "safe sex" except or oral as far as I knew and I have evidence that didn't work out for me (or maybe it was one of those rare oral cases) :-[   

As far as Isentress, I seriously think that one of the reasons for virologic failure being higher is that the dosing is BID and not daily. They have done studies with blood pressure medicine and found that adherence to treatment is much lower with 2x/day dosing... even if the pill works, it has to be in your blood to do its job.
7/10/13: Oraquick at Home (+)
7/11/13: CD4 <20, VL 286,000
7/26/13: Start Stribild, Bactrim, Azithromycin
8/13/13: CD4 64, VL 1194
9/11/13: CD4 87, VL 511
10/14/13: CD4 164, VL 34
10/15/13: Stop Azithromycin!

Offline oksikoko

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Re: Numbers on Virologic Failure
« Reply #9 on: August 25, 2013, 11:32:09 pm »
Self-reported 100% adherence is not super reliable.... I was 100% with "safe sex" except or oral as far as I knew and I have evidence that didn't work out for me (or maybe it was one of those rare oral cases) :-[   

As far as Isentress, I seriously think that one of the reasons for virologic failure being higher is that the dosing is BID and not daily. They have done studies with blood pressure medicine and found that adherence to treatment is much lower with 2x/day dosing... even if the pill works, it has to be in your blood to do its job.

:( I'm sorry to hear your story. Unless I'm the victim of a very not-funny joke, I infected someone via oral only, so I sympathize. I still cringe a little when I hear the "oral is safe" talk going too far.

That's very interesting about Isentress and dosing, and it makes complete sense. If you need it twice/day, the window must be awfully small as well. Maybe the glorious dolutegravir will help alleviate some of these issues. I'm hopeful it will eventually mean I can switch to something Stribild-like that doesn't require cobicistat. I've probably mentioned this, um, once or twice, haha.

Is there a comprehensive list of the window periods? I've heard that Stribild, for instance, is not as forgiving as Atripla in terms of taking your dose a little late, but I'd love to see across-the-board figures for various drugs.
Code: [Select]
2014-11-14: CD4 Wars Episode II: Return of the Stribild (released in Europe as Stribild II: Werewolf Bitch)
2014-11-06:                ☣ VL (→) 12,627      ☣ CD4 (→) 639
2014-??-??: off treatment  ☣ VL (?)              ☣ CD4 (?)
2013-10-03:                ☣ VL (=) undetectable ☣ CD4 (+) 1105
2013-05-23:                ☣ VL (=) undetectable ☣ CD4 (-) 945
2013-02-25:                ☣ VL (-) undetectable ☣ CD4 (+) 1123
2012-12-16: Enter Stribild
2012-11-20: HIV+           ☣ VL (→) 132,683      ☣ CD4 (→) 920
2012-04-01: HIV-
Dates in this signature file conform to ISO 8601. ;-)

If no one complains, nothing will ever change.

 


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