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Author Topic: Isentress Once-a-Day Study Being Halted  (Read 3675 times)

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Offline Inchlingblue

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Isentress Once-a-Day Study Being Halted
« on: November 29, 2010, 02:55:45 PM »
This kind of sucks. I have a few questions that are not addressed in these initial reports. For example:

Are they able to parse the data in order to see how once a day worked with someone starting with a high viral load versus a lower viral load?

Was there any difference in results depending on the other meds the participants were taking along with Isentress?

Is it still feasible to take once a day Isentress if a person is already undetectable?

They got all the way to Phase III before they noticed no non-inferiority?

Merck's HIV drug Isentress fails once-a-day study

By Ransdell Pierson
NEW YORK | Mon Nov 29, 2010 12:50pm EST
(Reuters) - Merck & Co said once-daily use of its HIV drug Isentress was less effective in a late-stage study than standard twice-daily dosing among patients that had not previously been treated for the virus that causes AIDS.

Based on the disappointing initial results, the U.S. drugmaker said on Monday it was ending the Phase III study, which could have paved the way for wider use among previously untreated patients.


Continued . . .

I've been on this med since mid 2009 and doing great. I take it twice a day and have gotten used to it, it's not a big deal for me to take it twice a day but it would have been nice to have once a day dosing as an option.

There are several people on this site taking it once a day and doing well.

LINKS:

http://www.reuters.com/article/idUSTRE6AS4DD20101129

http://online.wsj.com/article/SB10001424052748704584804575644820046988684.html?mod=googlenews_wsj

http://www.businessweek.com/ap/financialnews/D9JPS8981.htm
« Last Edit: November 29, 2010, 03:16:36 PM by Inchlingblue »

Offline ElZorro

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Re: Isentress Once-a-Day Study Being Halted
« Reply #1 on: November 29, 2010, 03:01:26 PM »
Yes, Inch, that is a bit disappointing and you're right, the extra pill isn't such a big deal, but fewer pills is certainly better in my mind. I, too, would be curious as to how they ended up all the way into a Phase III before the lightbulb came on. I guess it merits additional research into what the endpoints of the trial were....

Offline Inchlingblue

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Re: Isentress Once-a-Day Study Being Halted
« Reply #2 on: November 29, 2010, 03:10:47 PM »
Another article says:

Merck says the overall treatment difference was primarily due to results in patients with high viral load.

I'll bet once a day dosing works if a person does not start out with a super high viral load or if it's dosed once a day after a person becomes undetectable but I doubt they'll do a study to prove that.

LINK:

http://www.genengnews.com/gen-news-highlights/merck-ditches-phase-iii-study-evaluating-once-daily-dosing-of-hiv-drug-isentress/81244295/


Offline ElZorro

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Re: Isentress Once-a-Day Study Being Halted
« Reply #3 on: November 29, 2010, 03:27:58 PM »
I'm still trying to completely understand the role of the meds after undectable has been reached...I'll try to explain the "lack of understanding" before "you know who" jumps all over me  because I'm not completely ignorant as to why I'm going to take these pills everyday ;)

Very rarely, I get cold sores. When I do, I pop Valtrex for a day and, voila, the thing goes away in a week or so. Of course, there are very obvious symptoms that a cold sore is coming on, so I know when the virus has activated and I need to search for that purple pill.

My limited understanding is that HIV is similiar in the respect that at anytime after reaching undetectable, the virus can reactivate from the latent reservoirs and become a problem. Since there are no obvious signs that the virus is active again, one can't simply start meds to put it back in its place. So, instead, we keep the meds onboard for just such an emergency.  Does that make sense?  Am I completely wrong?

The VA considers < 75 as being undetectable and I know there are other tests that look <40 or <20. I wonder if at any of those levels, the body (if the immune system hasn't been cripled) is capable of controlling that little amount of virus with a lesser degree of help and if the full dose of the meds might only needed for a major "outbreak" from the reservoirs. If that were the case, it would be great if there was a way to check VL levels on a daily basis in the same manner that diabetics check their insulin levels to determine if they need to take action.

Please, it's really a question. If you don't have anything nice to say or contribute, just move on  :P  Thanks!

Offline madbrain

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Re: Isentress Once-a-Day Study Being Halted
« Reply #4 on: November 29, 2010, 05:18:59 PM »
This kind of sucks. I have a few questions that are not addressed in these initial reports. For example:

Are they able to parse the data in order to see how once a day worked with someone starting with a high viral load versus a lower viral load?

Was there any difference in results depending on the other meds the participants were taking along with Isentress?

Is it still feasible to take once a day Isentress if a person is already undetectable?

They got all the way to Phase III before they noticed no non-inferiority?

Merck's HIV drug Isentress fails once-a-day study

By Ransdell Pierson
NEW YORK | Mon Nov 29, 2010 12:50pm EST
(Reuters) - Merck & Co said once-daily use of its HIV drug Isentress was less effective in a late-stage study than standard twice-daily dosing among patients that had not previously been treated for the virus that causes AIDS.

Based on the disappointing initial results, the U.S. drugmaker said on Monday it was ending the Phase III study, which could have paved the way for wider use among previously untreated patients.


Continued . . .

I've been on this med since mid 2009 and doing great. I take it twice a day and have gotten used to it, it's not a big deal for me to take it twice a day but it would have been nice to have once a day dosing as an option.

There are several people on this site taking it once a day and doing well.

LINKS:

http://www.reuters.com/article/idUSTRE6AS4DD20101129

http://online.wsj.com/article/SB10001424052748704584804575644820046988684.html?mod=googlenews_wsj

http://www.businessweek.com/ap/financialnews/D9JPS8981.htm


Too bad ...
FYI, I tried to switch back to 2x a day a few weeks ago, I felt like refilling my pillbox differently that week. I had some noticeable nausea in the morning. Lack of breakfast is most likely a factor. I never get nausea now when I take both Isentress in the evening. I am still undetectable and will stick to 1x a day in the evening.

Offline Hoover

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Re: Isentress Once-a-Day Study Being Halted
« Reply #5 on: November 29, 2010, 07:43:47 PM »
Even with our affordable labs in CR, it still costs $200 per VL test....
Also it takes a week to run that test in CR.
With our socialized medicine, we get two free testings per year.

Daily testing could be price prohibiting, but I see the wisdom in your thought process.

Hoover
Infection date: March 16, 2010
20/05/10 - CD4 348  VL 58,000  Lymph nodes in jaw painful!  Antioxidants started.
01/06/10 - CD4 428  VL?
24/06/10 - CD4 578  VL 9,800
13/07/10 - CD4 620  VL?
04/09/10 - CD4 648  VL?
01/11/10 - CD4 710  VL?   CD8 972
16/12/10    CD4 738  VL?  CD8  896   
02/02/11    CD4 520 (month of parasites and new lab)
14/03/11 started Truvida and Sustiva (Efavirenz)
04/07/11 CD4 686 VL 75 CD8 588  41%
10/10/11 CD4 757  45%  VL UD

Offline Vertice

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Re: Isentress Once-a-Day Study Being Halted
« Reply #6 on: November 29, 2010, 11:44:20 PM »
Disappointing indeed. I was anxiously waiting for some news on this study, and I think is great to know that you shouldn't take once a day if you have high viremia.

What will be good to know is what exactly is considered high, and most importantly to me, how safe is to switch to Once Daily once you have reached undetectable numbers.
24 Jun 10  -  Isentress + Truvada

Offline ElZorro

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Re: Isentress Once-a-Day Study Being Halted
« Reply #7 on: November 29, 2010, 11:54:20 PM »
Daily testing could be price prohibiting, but I see the wisdom in your thought process.

Yeah, I'm sure you're right. I'm clueless when it comes to the testing they do. Chem was never my subject - I hated it. It was the only class I was ever in danger of failing (actually, I think that technically, I did fail). I threatened the teacher with the fact that if I didn't pass his required class I couldn't go to bootcamp and I would definitely come back to see him for summer school...It was the only D- of my life  ::)

Offline alejandroglz

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Re: Isentress Once-a-Day Study Being Halted
« Reply #8 on: November 30, 2010, 12:35:22 AM »

Hello, I been taking Isentress 2 pills at once and Truvada at the same time on the evenings (before bed).
My    doctor offer me this option like almost 6 months ago. I will get my labs next month. No sides effects so far.

@ Zorro - I hate chem too, u should try Microbiology, its fun and u will learn a lot about virus and bacterias lol
 ;D

05/09 poz
05/09 cd4 320 vl 500,000+
06/09 cd4 560 vl 442,000
07/09 cd4 460 vl 125,000 
09/09 cd4 389 vl 140,000
10/09 cd4 349 vl 148,000
11/09 cd4 350 vl 150,000 start Isentress/Truvada (11-18-09)
12/09 cd4 509 vl undetectable! As 12-03-09 + H1N1 vaccine
04/10 cd4 560 vl und
08/10 cd4 580 vl und start Isentress 2*400ml once a day/1truvada

Uno no vino al mundo a sufrir, arriba ese animo!

Offline Hellraiser

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Re: Isentress Once-a-Day Study Being Halted
« Reply #9 on: November 30, 2010, 04:22:23 AM »
Elzorro I think HIV is constantly reactivating in small quantities, thus why you have to maintain HAART.  It's not like once a month but a couple of times every hour or some such.

Offline Inchlingblue

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Re: Isentress Once-a-Day Study Being Halted
« Reply #10 on: November 30, 2010, 09:19:12 AM »
Elzorro I think HIV is constantly reactivating in small quantities, thus why you have to maintain HAART.  It's not like once a month but a couple of times every hour or some such.

Here's a layman's attempt at an explanation:

When a person reaches undetectable, Robert Siciliano found that the residual viremia is virus coming from the reservoirs, not virus that's actively replicating. As long as the right levels of meds are in one's system the virus is kept in check. If a person stops meds it usually takes at least several days if not weeks for the virus to be able to replicate again.

The various meds stop HIV at different points in its replication cycle. The reason it usually takes three medications from at least two different classes in order to halt HIVs replication is the virus's high mutation rate coupled with the fact that, being a retrovirus, it uses reverse transcription in order to replicate. This method of replication is very imperfect and results in many genetic "mistakes." This is  an advantage for the virus since all these genetic "mistakes," along with HIV's high replication rate, means that the virus can very rapidly evolve and become resistant to one or to two meds very easily.  Sometimes two meds can keep it in check but there's more of a risk of resistance. Three seems to be the magic number of meds that are needed in order to completely halt HIV's replication.

Once the virus is not replicating that means it can't mutate and become resistant. The only virus left at that point is virus in the reservoirs, which the meds can't reach. If meds are stopped, the virus in the reservoirs is able to wake up and start replicating since there's nothing preventing it from doing so. If the meds could reach the virus in the resrevoirs we'd all be cured.

A person with HIV not on treatment has several billion copies of new virus being produced every day and several billion T cells destroyed every day. That's the kind of war going on in one's body on a daily basis when HIV is not halted by the meds.

A virus such as HIV provides a picture of evolution at warp speed. The herpes virus, even in its various iterations, doesn't replicate as fast as HIV and doesn't use reverse transcription therefore it doesn't mutate as much so it's easier to control with just one medication. By the way, there is a concern that some herpes viruses can and will eventually become resistant to acyclovir (Valtrex is a form of acyclovir).

The reason Isentress once a day might work better after a person is undetectable is that once a person is undetectable there is very little virus left so it would stand to reason that having slightly lower levels of the meds might still be enough to keep it in check (i.e. before it has a chance to get to those billions-level of replication). Especially since the study found that  the overall treatment difference was primarily due to results in patients with high viral load.

LINK:

http://www.web-books.com/eLibrary/Medicine/Infectious/AIDS_Infection.htm


This thread has some useful info about the reservoirs:

http://forums.poz.com/index.php?topic=28249.msg348372#msg348372
« Last Edit: November 30, 2010, 10:04:51 AM by Inchlingblue »

Offline Inchlingblue

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Re: Isentress Once-a-Day Study Being Halted
« Reply #11 on: November 30, 2010, 09:39:03 AM »
Re: Isentress sales/profits I thought this was, um, interesting:

Merck, of Whitehouse Station, N.J., reported Isentress sales of $777 million for the first nine months of 2009, up 50% from a year earlier.

LINK:

http://online.wsj.com/article/SB10001424052748704584804575644820046988684.html?mod=googlenews_wsj

It's one of the highest priced HIV meds (maybe the highest), since Merck kept their salvage therapy price rather than re-price it once it was approved for first line use. It's on it's way to becoming a Billion Dollar a year drug.

I look forward to the day it's available from Cipla in India and sold online the way Viraday (generic Atrtipla) and Truvada are.
« Last Edit: November 30, 2010, 09:42:20 AM by Inchlingblue »

Offline Inchlingblue

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Re: Isentress Once-a-Day Study Being Halted
« Reply #12 on: November 30, 2010, 10:14:38 AM »
More specific info about the study:

http://www.aidsmap.com/news/Merck-halts-study-of-once-daily-raltegravir/page/1562177/


There was a real difference with those who started with viral loads over 100,000 but not so much otherwise. Also, the fact that after 48 weeks some were still not undetectable doesn't mean they had developed resistance.
 
I wonder if anyone actually developed resistance and if those who were still undetectable when the study was halted might have reached undetectable soon enough if they continued.

Offline ElZorro

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Re: Isentress Once-a-Day Study Being Halted
« Reply #13 on: November 30, 2010, 08:28:47 PM »
Elzorro I think HIV is constantly reactivating in small quantities, thus why you have to maintain HAART.  It's not like once a month but a couple of times every hour or some such.

Thanks, Hellraiser. I didn't realize it was that active. I guess I was looking at "latent" as "dormant" which is more inline with what the herpes cold sore virus is like.

If figures..I finally get "someone" in my life that likes to "reproduce like bunnies" and he wants to kill me.  :P

Offline ElZorro

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Re: Isentress Once-a-Day Study Being Halted
« Reply #14 on: November 30, 2010, 08:48:40 PM »
Thanks for the layman's explanation, Inch. As always, it's great! Especially the quoted part, which is sort of where I was going in my train of thought. Wondering if a reduction in the amount of on-board meds might be warranted once undetectable has been reached. One of the things I've been reading (since dropping Atripla) is that folks successfully reduce the amount of Sustiva they are on if they experience intolerable side-effects. I wasn't aware of that when I switched (although I hope to never take that drug again since I love what I'm on). It makes sense to me that "one size doesn't fit all". Of course, it's probably not practical (or possible) to determine the optimal dosing for each individual person.

I'm fine (at least today) with the prospect of having to take these drugs for however long I need to take them. Of course, I'm all for reducing the amount of (non-lube based) chemicals I put into my body.

The current research is exciting. On some level, I wish I had the experience and knowledge of some of the LTS out here so that I had a yardstick by which to measure the validity of the trials that we discuss here. It's one thing to reference "the old days of AZT" and "T-cell naming parties" and another to have the experience to be able to recognize exactly how far things have progressed in the last 20? 15? 10? 5? years and to evaluate the research data this is published. Recently, in another post about Red Day on Facebook, the Rev made a comment that he felt is was (paraphrase) "more reasonable to think that there won't be another child born with HIV by 2015". To me, that statement was absolutely stunning. To think that experienced, knowledgeable people are actually raising the possibility of halting, completely, one avenue by which people contract HIV. (I hope that I haven't misinterpreted misrepresented what he posted  :P )

Again, thanks for taking the time to share your understanding.  ;)

The reason Isentress once a day might work better after a person is undetectable is that once a person is undetectable there is very little virus left so it would stand to reason that having slightly lower levels of the meds might still be enough to keep it in check (i.e. before it has a chance to get to those billions-level of replication). Especially since the study found that  the overall treatment difference was primarily due to results in patients with high viral load.
« Last Edit: November 30, 2010, 09:06:07 PM by ElZorro »

Offline mewithu

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Re: Isentress Once-a-Day Study Being Halted
« Reply #15 on: November 30, 2010, 09:00:56 PM »
 I think twice a day is no big problem. I think all the meds work better at twice a day because it gives your body a better chance to keep the meds in you longer and fight the disease better.
1997 is when I found out, being deathly ill. I had to go to the hospital due to extreme headache and fever. I fell coma like,  two months later weighing 95 pounds and in extreme pain and awoke to knowledge of Pancreatis, Cryptococcal Meningitis, Thrush,Severe Diarea,  Wasting, PCP pneumonia. No eating, only through tpn. Very sick, I was lucky I had good insurance with the company I worked for. I was in the hospital for three months that time. 
(2010 Now doing OK cd4=210  VL= < 75)
I have become resistant to many nukes and non nukes, Now on Reyataz, , Combivir. Working well for me not too many side effects.  I have the wasting syndrome, Fatigue  . Hard to deal with but believe it or not I have been through worse. Three Pulmonary Embolism's in my life. 2012 520 t's <20 V load

Offline Inchlingblue

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Re: Isentress Once-a-Day Study Being Halted
« Reply #16 on: November 30, 2010, 09:50:21 PM »
I think twice a day is no big problem. I think all the meds work better at twice a day because it gives your body a better chance to keep the meds in you longer and fight the disease better.

Not all meds work better twice a day, it just depends. The dosing and the potency (milligrams) of any given medication is based on its pharmacokinetics, or in very general terms, how long the drug remains in one's body at levels strong enough to have an effect. Drugs that have a longer half life should not be taken twice a day,

There are many medications that are dosed once a day and should not be dosed or taken more than that.

One of the things I've been reading (since dropping Atripla) is that folks successfully reduce the amount of Sustiva they are on if they experience intolerable side-effects.

Ann's husband had Therapeutic Drug Monitoring (TDM) done, where they measure the drug levels and are able to determine if a particular individual is able to maintain high enough drug levels despite a lower dosage. 

Offline ElZorro

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Re: Isentress Once-a-Day Study Being Halted
« Reply #17 on: November 30, 2010, 10:14:11 PM »
Ann's husband had Therapeutic Drug Monitoring (TDM) done, where they measure the drug levels and are able to determine if a particular individual is able to maintain high enough drug levels despite a lower dosage. 

That's good to know. I'll have to mention it to my ID next time we meet to see if that's an option the VA might offer. Thanks for the tip.

Offline ElZorro

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Re: Isentress Once-a-Day Study Being Halted
« Reply #18 on: December 02, 2010, 06:25:48 PM »
from http://www.thebody.com/content/art59673.html?ic=700100

"The major difference, of course, is that even the once-daily raltegravir arm in this study did quite well -- an 83% response is not too shabby.

It's just that today, our standard-of-care for first-line therapy is (wonderfully) high, and the twice-daily treatment arm had an 89% success rate, with the advantage seen in particular in patients with HIV RNA > 100k. The difference in response put the once-daily approach just outside of the protocol-specified criterion for non-inferiority."

 


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