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Author Topic: Made the switch to Isentress  (Read 5433 times)

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Offline Patrick

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Made the switch to Isentress
« on: January 09, 2009, 08:57:34 PM »
And have absolutely NO side-effects!  zip, zero, nada.  Like taking a sugar pill.  Been on it for about a month now.  The diahrreah I had from Kaletra vanished one day after I made the switch.  I'm not looking back!   ;D
Seroconversion - late October 07
11/14/07 - CD4 190   VL >750,000
11/14/07 - Started Truvada & Kaletra
12/5/07 - CD4 851     VL 710
2/19/08 - CD4 604     VL Undetectable
5/8/08 -   CD4 829     VL Undetectable
8/12/08 - CD4 915     VL 80 (blip)
11/11/08 - CD4 967    VL Undetectable

Offline veritas

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Re: Made the switch to Isentress
« Reply #1 on: January 10, 2009, 04:05:31 AM »

Good to hear Patrick. I've been on Isentress for a little over a year now with no adverse affects and an ud vl. Be sure to take this med on time as directed due to the fact it has a low barrier to resistance. Your numbers look great!

veritas

Offline ChefDD

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Re: Made the switch to Isentress
« Reply #2 on: January 11, 2009, 11:05:32 AM »
That is good to hear!  I will be switching from Kaletra to Isentress in a few weeks. My dr will need to watch closely because of an allergy to sulfur drugs. Isentress has a sulfonamide component which the Tibotec warns about. Good luck!!  ChefDD
ChefDD ( White Whisker )

Offline ChefDD

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Re: Made the switch to Isentress
« Reply #3 on: January 11, 2009, 11:28:53 AM »
I'm wrong about Isentress :-\ Prezista is the drug connected to a sulfur component. I will be starting 4 new hiv meds and got confused. Will you be on a protease because Isentress is a whole new category of med?   ChefDD
ChefDD ( White Whisker )

Offline Miss Philicia

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Re: Made the switch to Isentress
« Reply #4 on: January 11, 2009, 12:07:16 PM »
I've been on Isentress now for 14 months and it's definitely the most side effect free HIV medication for me -- and I've been on 18 of them.
"Iíve slept with enough men to know that Iím not gay"

Offline denb45

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Re: Made the switch to Isentress
« Reply #5 on: January 11, 2009, 02:19:14 PM »
And have absolutely NO side-effects!  zip, zero, nada.  Like taking a sugar pill.  Been on it for about a month now.  The diahrreah I had from Kaletra vanished one day after I made the switch.  I'm not looking back!   ;D

The same here, been on Isentress for 2 yrs now, but still have the the hershey squirts tho, but that's due to the Norvir I take twice a day, not really much I can do about that, however, Imodium 2MG or more a day helps some, but not much...... ??? I do understand that it's part of my AIDS/HIV disability, and that I have been living with that for well over 15 yrs. (the Hershey squirts) so, I'm kinda used to it by now, it's something I've kinda learned to live with..........

« Last Edit: January 11, 2009, 02:24:21 PM by denb45 »
"it's so nice to be insane, cause no-one ask you to explain" Helen Reddy cc 1974

Offline Patrick

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Re: Made the switch to Isentress
« Reply #6 on: January 12, 2009, 09:48:34 PM »
Thanks everyone.  Veritas, I'm a little bummed that Isentress has a low barrier to resistance, as the high barrier to resistance Kaletra had is what I loved about it the most.  Made me feel safe.  I am proud to say that I've never missed a dosage of meds in my short 1+ year with HIV, and I most certainly do not plan to change that.  I faithfully take my Isentress every 12 hours, give or take 15 min. 

What I'd like to know is if treatment failure is expected to occur on meds that have a low barrier to resistance even if the patient takes the medicine faithfully?  Or does it just require extra diligence in taking it as scheduled so that resistance will not occur.......I'm still learning here so any input appreciated.

Oh and ChefDD - no protease inhibitors for me now.  The regimin is Truvada and Isentress.  Although my doc says I should have no problem going back on Kaletra if I were ever want or need to.
Seroconversion - late October 07
11/14/07 - CD4 190   VL >750,000
11/14/07 - Started Truvada & Kaletra
12/5/07 - CD4 851     VL 710
2/19/08 - CD4 604     VL Undetectable
5/8/08 -   CD4 829     VL Undetectable
8/12/08 - CD4 915     VL 80 (blip)
11/11/08 - CD4 967    VL Undetectable

Offline freestate guy

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Re: Made the switch to Isentress
« Reply #7 on: January 13, 2009, 12:18:50 AM »
Patrick - Where did you hear that Isentress has a "low barrier to resistance"? I'm not exactly sure what you mean by that, but if it is that you have to take it precisely every twelve hours, I don't think you are right. While adherence is obviously very important, I am under the impression from my doctor that Isentress has a long "half life" and that you don't have to be as precise in dosage as with some other drugs. I have been on Isentress/Truvada for 13 months with good numbers, undetectable VL, and no significant side effects.
Mitochondriac

Offline freestate guy

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Re: Made the switch to Isentress
« Reply #8 on: January 13, 2009, 12:26:09 AM »
Sorry, I see that you got that idea of a "low barrier of resistance" from a prior post of Veritas. Again, I'm not sure that it is right.
Mitochondriac

Offline Miss Philicia

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Re: Made the switch to Isentress
« Reply #9 on: January 13, 2009, 01:01:02 AM »
source

PI Perspective #47

December 2008   

Study data explain Isentressí excellent resistance profile
by Paul Dalton

A presentation at the joint 2008 ICAAC / IDSA meeting in Washington, DC helps deepen our understanding of Merckís integrase inhibitor, Isentress (raltegravir). The talk by Daria Hazuda showed how resistance develops to Isentress and poses a possible explanation for its unparalleled ability to reduce HIV levels quickly.

Hazuda reported on an analysis of the BENCHMRK 1 and 2 studies, which were the basis for Isentressí FDA approval. In these studies, people with extensive experience taking HIV drugs were randomly assigned to take either Isentress or a placebo, each taken with optimized background therapy (or the best available combination of HIV drugs chosen with the aid of resistance testing).

Overall it was rare to develop resistance to Isentress in these studies. When people did, they tended to develop mutations that had been seen in earlier research, particularly at positions 148 and 155. This analysis found that over time people tended to accumulate more resistance mutations, and the pattern of mutations tended to evolve from mostly 148 to mostly 155. This may be important, as the 155 mutation is more damaging to HIVís ability to replicate, called viral fitness, than 148.

Perhaps of more interest is the finding that the likelihood of experiencing treatment failure on Isentress was not related to concentrations of the drug measured in the blood. Rather, it seems to be related to the amount of time the drug remains bound or attached to the integrase enzyme, called its off-rate.

It appears that Isentress, and other integrase inhibitors, stay attached to the integrase-HIV complex longer than they are measurable in the blood. This might explain why Isentress reduces HIV levels more quickly than other HIV drugs, as it retains activity longer than it is measurable in the blood.

Isentress has proven a very successful option for many people who had few HIV treatment options. Resistance to Isentress remains rare, but this study helps us better understand how it does develop. It also may help us understand the drugís unique ability to reduce HIV levels more quickly than other drugs.
"Iíve slept with enough men to know that Iím not gay"

Offline veritas

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Re: Made the switch to Isentress
« Reply #10 on: January 13, 2009, 05:39:35 AM »

Didn't mean to be an alarmist. Was referring to the number of mutations needed to render Isentress less susceptible due mostly to non-adherence.






Resistance to raltegravir is associated with the selection of 1 or more of several resistance mutations; however, the resistance profile of raltegravir in human subjects has not been characterized fully. In vitro and in vivo studies of raltegravir show the emergence of a number of integrase mutations. In the limited clinical data currently available, two main genetic pathways to resistance have been identified. These involve Q148H/K/R plus additional mutations (E138K, G140A/S) or N155H plus additional mutations (L74M, T92Q, T97A, V151I, G163R). Increasing numbers of these mutations, as well as specific combinations, appear to be associated with greater degrees of reduced susceptibility to raltegravir.(6)

The study that Miss Philicia posted is more up to date which I was unaware of --- thankyou Dave.

veritas

Offline BM

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Re: Made the switch to Isentress
« Reply #11 on: January 13, 2009, 08:07:49 AM »
Are there any studies comparing the susceptibility of raltegravir-resistant virus to elvitegravir?

Offline veritas

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Re: Made the switch to Isentress
« Reply #12 on: January 13, 2009, 09:16:05 AM »

Offline Miss Philicia

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Re: Made the switch to Isentress
« Reply #13 on: January 13, 2009, 10:33:42 AM »


The study that Miss Philicia posted is more up to date which I was unaware of --- thankyou Dave.

veritas


Indeed.  But I have seen wording like that which you mentioned, so I'm left scratching my head as well.  You may note that the selection that I posted comes from our very own Paul Dalton, from the AIDSmeds/poz.com blog section.  He's very dependable for this sort of thing.

I've also not heard any cautionary advice from my doctor, and he's one of the very top ones in Philadelphia and has many, many patients on this medication going back through the drug trials.
"Iíve slept with enough men to know that Iím not gay"

Offline veritas

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Re: Made the switch to Isentress
« Reply #14 on: January 13, 2009, 11:05:08 AM »

From your quote Dave:



"Perhaps of more interest is the finding that the likelihood of experiencing treatment failure on Isentress was not related to concentrations of the drug measured in the blood. Rather, it seems to be related to the amount of time the drug remains bound or attached to the integrase enzyme, called its off-rate."

A little concerning since I don't understand what it means and if I'm reading this right one can become resistant with full adherence.

One thing for sure nothing is ever easy with this disease!

veritas

Offline denb45

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Re: Made the switch to Isentress
« Reply #15 on: January 13, 2009, 11:26:54 AM »
From your quote Dave:



"Perhaps of more interest is the finding that the likelihood of experiencing treatment failure on Isentress was not related to concentrations of the drug measured in the blood. Rather, it seems to be related to the amount of time the drug remains bound or attached to the integrase enzyme, called its off-rate."

A little concerning since I don't understand what it means and if I'm reading this right one can become resistant with full adherence.

One thing for sure nothing is ever easy with this disease!

veritas

I wouldn't worry about it to much, if I were you, speaking of resistant with full adherence, every time I go see my ID Doctor, and it becomes time for a new combo, I'm always referred to as " Mr. Resistance"
thats right ,I'm resistant to just about everything that's out there as far as Med combo's go, and that leaves me very little choice in that area, but some how, things always work out, at least for a while.....
the Meds only work for so long, but, I'm used to it, so, I don't worry about it much at all...... ;D
« Last Edit: January 13, 2009, 11:32:59 AM by denb45 »
"it's so nice to be insane, cause no-one ask you to explain" Helen Reddy cc 1974

Offline Miss Philicia

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Re: Made the switch to Isentress
« Reply #16 on: January 13, 2009, 11:33:19 AM »
From your quote Dave:

"Perhaps of more interest is the finding that the likelihood of experiencing treatment failure on Isentress was not related to concentrations of the drug measured in the blood. Rather, it seems to be related to the amount of time the drug remains bound or attached to the integrase enzyme, called its off-rate."

A little concerning since I don't understand what it means and if I'm reading this right one can become resistant with full adherence.

One thing for sure nothing is ever easy with this disease!

veritas

Yeah, I saw that and didn't really get it either.

ps:  it's always David, not Dave :)
"Iíve slept with enough men to know that Iím not gay"

Offline Inchlingblue

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Re: Made the switch to Isentress
« Reply #17 on: January 19, 2009, 05:41:39 PM »
Patrick:

I've been reseacrhing Isentress's low barrier to resistance and what I have come up with is:

1) When looking at drugs with low barrier to resistance, the other thing to look at is how powerful they are in disabling HIV and Isentress seems to be powerful, therefore, that  supposedly "offsets" the fact that it has a low barrier to resistance (Sustiva also has low barrier to resistance but is considered powerful also). Isentress went head-to-head with Sustiva and the numbers were comparable, if actually a little better (among treatment-naive patients)
see link: http://www.aidsmeds.com/articles/1667_12618.shtml

2) Isentress must of course be combined with two other drugs that you are not resistant to in order for it to work.

Despite the above, 100% adherence is key. I'm not yet on any meds and I am thinking that Isentress and Truvada might be a good combo for me, still ding research and have not yet discussed it with my MD.

Hope the info helps.

Offline Patrick

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  • Where the determination is, the way can be found.
Re: Made the switch to Isentress
« Reply #18 on: January 20, 2009, 12:33:44 AM »
Thanks for that Inchlingblue, much appreciated!
Seroconversion - late October 07
11/14/07 - CD4 190   VL >750,000
11/14/07 - Started Truvada & Kaletra
12/5/07 - CD4 851     VL 710
2/19/08 - CD4 604     VL Undetectable
5/8/08 -   CD4 829     VL Undetectable
8/12/08 - CD4 915     VL 80 (blip)
11/11/08 - CD4 967    VL Undetectable

Offline Inchlingblue

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Re: Made the switch to Isentress
« Reply #19 on: January 23, 2009, 07:32:37 PM »
From your quote Dave:



"Perhaps of more interest is the finding that the likelihood of experiencing treatment failure on Isentress was not related to concentrations of the drug measured in the blood. Rather, it seems to be related to the amount of time the drug remains bound or attached to the integrase enzyme, called its off-rate."

A little concerning since I don't understand what it means and if I'm reading this right one can become resistant with full adherence.

One thing for sure nothing is ever easy with this disease!

veritas

Quite the opposite. Usually in order to determine dosage for any medication, they look at levels of it in the blood and determine the half-life. With Isentress, what they have seen is that looking at the level in the blood is not the whole picture, since it binds to the integrase enzyme for a long time. This is why they are conducting clinical trials with once daily dosing, in order to determine if, given it's longer binding-time to the integrase enzyme, once daily dosing might suffice. Here's a link with my source:

http://www.thebody.com/Forums/AIDS/Meds/Current/Q198101.html

Offline veritas

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Re: Made the switch to Isentress
« Reply #20 on: January 24, 2009, 05:17:58 AM »

Inchlingblue,

Thanks for the link. It explains that Isentress has the potential for once daily dosing which is great, however, since resistance can develop to Isentress, my question is: Is the resistance a factor of non-adherence or the length of time the drug remains bound the integrase enzyme and what does that mean?

David's link seems to suggest that the offrate is the key to resistance and that is my concern. I don't understand what that means. From your link, blood concentration half-life is not a factor for once daily dosing.

Confused! Can anyone shed some light on this mechanism?

veritas

Offline Inchlingblue

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Re: Made the switch to Isentress
« Reply #21 on: January 24, 2009, 05:36:03 PM »
Inchlingblue,

Thanks for the link. It explains that Isentress has the potential for once daily dosing which is great, however, since resistance can develop to Isentress, my question is: Is the resistance a factor of non-adherence or the length of time the drug remains bound the integrase enzyme and what does that mean?

David's link seems to suggest that the offrate is the key to resistance and that is my concern. I don't understand what that means. From your link, blood concentration half-life is not a factor for once daily dosing.

Confused! Can anyone shed some light on this mechanism?

veritas

Veritas (nice name, by the way),

As I'm sure you know, adherence is key with Isentress as it is with all other HIV meds and, of course, it must be combined with at least 2 other appropriate meds that there is not any resistance to......Having said that, I agree with you that the wording from the article about Isentress quoted above can sound confusing (relating resistance  "to the amount of time the drug remains bound or attached to the integrase enzyme, called its off-rate."). I don't read it to mean that  Isentress has a bad resistance profile, though, in fact the title of the article that the quote is taken from is "Study Data Explain Isentress' Excellent Resistance Profile." The fact that Isentress binds to the integrase enzyme for a long time is a good thing, it's a measure of its potency. To say that Isentress resistance is "related to the amount of time the drug remains bound or attached to the integrase enzyme, called its off-rate" they mean as opposed to being related to levels of Isentress in the blood. Maybe reading the whole piece would help, here is a link:

http://www.thebody.com/content/art49168.html

Also, below is another link that I thought was very informative and helpful, in it Dr. Joel Gallant discusses highlights from the 2008 ICAAC/IDSA conference. He talks about several issues, including Isentress and specifically talks about his opinion regarding adherence/resistance issues in general at the very end of the piece:

http://www.thebodypro.com/content/confs/icaac2008/art49232.html

Offline veritas

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Re: Made the switch to Isentress
« Reply #22 on: January 25, 2009, 06:13:25 AM »

Inchlingblue (I was wondering what that meant?),

Thank's for the links. I get the jist of what the articles are telling me. I guess the offrate is the same for everyone if I'm reading it correctly. Assuming no mutations.

I liked your second link. Dr. Gallant is a knowledgeable guy and I enjoy reading his opinions. I'm sure you are aware of his website with Q&A's about HIV. If not you can find it here:

http://www.hopkins-hivguide.org/q_a/index.html?categoryId=9352&siteId=7151



veritas

Offline Inchlingblue

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Re: Made the switch to Isentress
« Reply #23 on: January 25, 2009, 05:04:58 PM »
Inchlingblue (I was wondering what that meant?),

Thank's for the links. I get the jist of what the articles are telling me. I guess the offrate is the same for everyone if I'm reading it correctly. Assuming no mutations.

I liked your second link. Dr. Gallant is a knowledgeable guy and I enjoy reading his opinions. I'm sure you are aware of his website with Q&A's about HIV. If not you can find it here:

http://www.hopkins-hivguide.org/q_a/index.html?categoryId=9352&siteId=7151

Veritas:

The "Inchling" part is from a poem by Wallace Stevens that I like (called "Bantams in Pinewoods') and the "blue' is b/c I like the color blue ;)

Yes, the off-rate would seem to be the same for everyone, more a product of Isentress and how it interacts with the integrase enzyme. The reason I had sent you that first link about the studies to determine once-daily dosing of Isentress was to illustrate, albeit indirectly, that very point. They are looking at the "off-rate" in order to determine if taking a certain dosage only once-a-day could work (as opposed to the current twice-a-day), depending on what they find out more specifically about the off-rate, i.e. how long it binds to the integrase enzyme, the new guidelines might change to once-a-day which would, of course, be way more convenient. The bottom line is that, in the case of Isentress they are looking at the off-rate, as opposed to the levels of Isentress in the blood (which is what they normally look at with most other drugs in order to determine dosing, etc).

I wasn't aware of Dr. Gallants website, that's awesome, thank you so much for mentioning it@!

 

 


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