Success Rate Genotype 1

[Jackie]

I was wondering about this posting that came up earlier and decided to do some checking. Here is what I found at the John Hopkins site.


Here is the link

http://hopkins-id.edu/index_ask.html

Jackie

P.S. # 4 is done!

[hyperhepper]

Hi Jackie, thanks for the info, it looks like an interesting site. But I'm so tired of reading about this stuff that my head is spinning. Could you tell me specifically what got your attention, and what it was you found out about geno. 1's.

Thanks,   ;)marina


PS - glad to hear # 4 went well, what do we have left, about 150 or so ?  

[Jackie]

Sure,
Sorry I thought my link went right to it. I never checked I guess. Here is the Question to the Dr that caught my attention. I am also putting the 2nd responce because it is Very inportant.  

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Change in Combo Results?
By Mark S. Sulkowski, M.D. (25-Feb-2003)

Q.) I am Gentotype 1a, with a "no-scarring" biopsy and normal ALT levels as of this year, so am waiting on treatment given the low success rate and side effects of treatment.

The last studies I read indicated a success rate of 38% for Genotype 1 combo treatment. A medical person now tells me that further studies have indicated a 60% success rate for Genotype 1.

Can you clarify which, if either, of the above success rates is most accurate?

Thank you!  
 
A.)  Well, 60% seems a bit overly optimistic when you look at all people with HCV genotype 1

However, when you look at two groups the picture is quite diffrent:

1) HCV genoptype 1 and high HCV RNA level (viral load) > 2 million copies or about 850,000 IU/mL

SVR with PEG/RBV for 48 weeks > 60%. In the PEG-IFN alfa-2b/RBV study the SVR was 73%

2) HCV genotype 1 and low HCV RNA level

SVR with PEG/RBV for 48 weeks ~ 30-40%

So, I think we can give more specific estimates for those with HCV genotype 1 by including HCV RNA level in the equation.
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RESPONSE

Q.)Didn't you reverse the HCV RNA levels?

 
A.) Woops - sorry! Good pick up. Low HCV RNA is always more responsive to therapy. I think I had not had my second cup of coffee that day. But, switch it around and the numbers are correct.

===================================

Coffee time for me too!

Have a good day
Jackie

[surfergirl]

Jackie,
So your saying that the last past years when my viral load was between 669,000 and 785,000 I had a better chance at success? Just my luck because now this year it went up to 6 million plus. My Doctor said that didn't make a difference. I don't know, I agree with Marina my head is spinning too. This is a strange dicease, evertime I think I got it figured out, something changes it again.
:-/

[hyperhepper]

 Well, let me say something here. Research has shown that low viral loads are easier to treat meaning faster viral clearance, BUT I gotta tell you that I've heard of people with low viral loads not clearing, or clearing after 24 weeks as opposed to 12, and I've also heard people clearing this virus with a pretreatment viral load of ll million. This is all a crapshoot. This thing is totally unpredictable. The good news is that I heard BILN is moving into phase 3. This will make it easier for people that have a resistant virus.   :)marina

[Jackie]

Well all I gotta say is that this is clearly an ongoing study. Depending on how each of us respond to treatment is what holds the key.

I think these studies are so new and have so many different factors that it is hard to say. I don't care if I have 1 or 100,000,000 viral load. I'm gonna beat this thing.  

So please take that Johns Hopkins Q/A deal with a grain of salt. I believe you can ask the next Dr and they will give you different numbers. My Dr said I had better than a 60% chance and thats what made me start tx.

The whole of it is to stay positive and focused and we will prevail!!

Jackie

[geow]

The below describes BILN, also known on this bulletin board previously as the new Pro-tease inhibitor. Only this time it is Johns Hopkins talking about. This very well looks like the cure so many have been looking for with this HCV disease.   George


Orally available Hepatitis C Virus (HCV) Protease Inhibitor (BILN 2061, Boehringer Ingelheim Pharma) Demonstrates Potent Anti-viral Activity in Persons Infected with HCV Genotype 1

Written by Mark Sulkowski, MD, Johns Hopkin University School of Medicine


The results of two studies presented at the 53rd Annual Meeting of the American Association of the Study of Liver Disease (AASLD) provided a stunning glimpse into the future of HCV therapy and shook the foundation of the new 2002 NIH Consensus Statement on the Management of Hepatitis C.

Researcher presented four papers describing the discovery, safety and early antiviral activity of BILN 2061, a serine protease inhibitor (Hepatology Volume 36 October 2002).

Abstract 464. Lamaree and colleagues from BI reported the discovery of a small, selective and potent inhibitor of the NS3 serine protease. The drug, BILN 2061, demonstrated potent in vitro activity and good pharmacokinetics and safety in animal species. Furthermore, BILN 2061 demonstrated low nanomolar inhibition of replication in the replicon cell model system. Based on these data, the drug was selected for further evaluation in man.

Abstract 800. Narjes and coworkers reported on the tolerability and pharmacokinetics of BILN 2061 after oral single doses (5 to 2400 mg) in healthy male subjects. The study evaluated increasing doses of the drug in groups of 8 mean (6 active drug and 2 placebo) and found no serious adverse events. The maximum tolerated dose was 2000 mg since the higher dose was limited by minor intestinal adverse events. The medication was administered in a PEG 400:ethanol solution and demonstrated pharmacokinetics evidence to support twice daily dosing of up to 200 mg with or without food.

Abstract 866. Hinrichsen and colleagues presented the results of the initial phase 1 study of BILN 2061 in 31 patients with HCV genotype 1 infection and minimal liver fibrosis. Subjects were treated with placebo, 25 mg, 200 mg or 500 mg of BILN 2061 given twice daily by mouth for two days with 10 -14 days of follow-up after treatment. The mean age of subjects was 47 years and 48% were HCV treatment naive. The serum HCV RNA level decreased by greater than one (1.0) log10 in 7 of 9 subjects at the 25 mg dose and 8 of 8 subjects at the 200 and 500 mg dose. No differences were noted in the responsiveness of interferon naive patients and those who had previously failed interferon based therapy. HCV RNA levels returned to baseline within 1 - 7 days after stopping the drug. Tolerability was good and no safety issues were identified among the 25 active drug recipients including clinical, laboratory and ECG assessments.
Abstract 563. Benamou and coworkers reported on the safety, tolerability and antiviral effect of BILN 2061 after oral treatment over two day in subjects with HCV genotype 1 and significant liver fibrosis (Ishak stage 3 and 4 but not cirrhosis). In a randomized, double-blind group comparison, 10 patients were treated with BILN 2061 200 mg orally twice daily or placebo for 2 days (8 active drug and 2 placebo). The mean age of the patient was 46 years and 50% were HCV treatment naive. All 8 patients treated with BILN 2061 demonstrated at least a two (2.0) log10 decrease in serum HCV RNA level at the end of the two day dosing period (Cobas Amplicor Monitor v2.0) and 2 patients had a decrease of greater than three (3.0) log10. After stopping therapy, the HCV RNA level returned to baseline in all subjects. No safety issues were identified by analysis of adverse events, vital signs, routine laboratory tests, and ECG.

Phase 2 studies of BILN 2061 for patients with chronic HCV are currently planned in the United States and Europe in early 2003.
http://www.natap.org/2002/AASLD/day14.htm

[Jackie]

Hey thats the same Dr that did the other one I posted.
Go figure.

Jackie

[hyperhepper]

  Right On Jackie, that's exactly the approach we all need to take, and believe that we will beat this. Numbers are great, and statistics give us information, but there is nothing like the power of the mind, and having faith, and staying positive !  

Geow, thanks for the info on BILN. I'd be interested to know if there's anything more recent. If you come across anything please share with us.  

[geow]

 Nov 2-5, 2002, Boston, MA

AASLD
(American Association for the Study of Liver Diseases)

http://www.natap.org/2002/AASLD/ndxAASLD.htm

The link above was a report of the conference of the AASLD held in November 2003.

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OK, here is a paragraph from an April 2003 report done by researchers at 2 Texas Unniversitys.

The immune system has many ways to detect and fight off invading microbes, and microbes have just as many ways to elude and disarm immune system components. Through a series of experiments on cells grown in the laboratory, Drs. Gale and Lemon defined the strategy HCV uses to evade the host's immune response. As HCV begins to replicate in its human host, it manufactures enzymes, called proteases, which it requires to transform viral proteins into their functional forms. The Texas investigators determined that one viral protease, NS3/4A, specifically inhibits a key immune system molecule, interferon regulatory factor-3 (IRF-3). IRF-3 orchestrates a range of antiviral responses. Without this master switch, antiviral responses never begin, and HCV can gain a foothold and persist in its host. Next, the scientists searched for ways to reverse the IRF-3 blockade. They applied a protease inhibitor to human cells containing modified HCV. This prevented the virus from making functional NS3/4A and restored the cells' IRF-3 pathway. Follow-up studies have shown that once restored, the immune response reduced viral levels to nearly undetectable levels within days, according to Dr. Gale.


and here is a link to the above paragraph which is the 2nd paragraph in the article..http://www.natap.org/2003/april/042103_10.htm

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So as you can all see, there is hope for us. For us in the throws of this trial and tribulation yes, it is difficult, I will not say it isn't. There is a saying in AA like this, "When you're sick and tired of being sick and tired, you can simply quit drinking." And so when I found out I had this HCV Virus, and after I started taking the TX, and felt generally sick, well, you can imagine for yourself the kind of advice I was getting.
  It made me way worse for these well meaning  recovering alkies to give me all that "you can quit at anytime BS."  You see, we cannot simply quit this thing, we have to do more. That is why this place means so much to me, I feel less crazy hearing you say, it can be done, but it aint no picnic. You all know, we are sick.
         The thing that does help me from those rooms however is, I can do this or, get thru this "one day at a time."  So for that as it is, yes I am sick, yes there is hope, and yes one day at a time, I will hopefully get thru this trial in my life.

George

[Jackie]

Wow!

I wish they had a smiley face with clapping hands cause I applaud you!

One day at a time........indeed is what we are going through. And we are all here for each other for those days we don't think we can go through another.

Thank you very much

Jackie

[hyperhepper]

 That's right...I couldn't agree more. And believe it or not I think this experience in our lives will make us stronger for us , and more compasionate for others, and their trials.

[Jackie]

Agreed! I know it has changed me and my thinking.  It has also shown me that I am not alone and do not have to go through it alone. I hope I can give as much to people as I have received in support, knowledge and friendship. It means alot just being able to share your experiences.

Thanks

Jackie  

[Penney]

Hey there everyone,

Somewhere in all my researches within the past 2 years I have learned that you can research TOO MUCH.....sometimes too much information is as bad as no information.  

I know, for me, I can drive myself nuts with all this and take no time out to just try to enjoy life without "obsessing" on the next bout of information.  Right now, I need to just plain 'enjoy' myself.......

Take care everyone, and just know that a positive attitude holds a lot of water!!!!!!!!!!!!!!!!


Penney

[geow]

Hi Jackie.
I reversed the numbers for the errant Doctor. It concused me for way too much time.
                               George

========================================
Change in Combo Results?
By Mark S. Sulkowski, M.D. (25-Feb-2003)  

Q.) I am Genotype 1a, with a "no-scarring" biopsy and normal ALT levels as of this year, so am waiting on treatment given the low success rate and side effects of treatment.

The last studies I read indicated a success rate of 38% for Genotype 1 combo treatment. A medical person now tells me that further studies have indicated a 60% success rate for Genotype 1.

Can you clarify which, if either, of the above success rates is most accurate?

Thank you!  
   
A.)  Well, 60% seems a bit overly optimistic when you look at all people with HCV genotype 1  

However, when you look at two groups the picture is quite different:  

1) HCV genotype 1 and high HCV RNA level (viral load) > 2 million copies or about 850,000 IU/mL
 
SVR with PEG/RBV for 48 weeks ~ 30-40%

2) HCV genotype 1 and low HCV RNA level

SVR with PEG/RBV for 48 weeks > 60%. In the PEG-IFN alfa-2b/RBV study the SVR was 73%




So, I think we can give more specific estimates for those with HCV genotype 1 by including HCV RNA level in the equation.  
===================================



~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
PS    The Doctor I spoke with about the above, whom had the 80-80-80 theory, I do not remember it being in the conversation as to which genotype of HCV I had.
The most interesting part was that ALL who fail to clear the virus are counted as non-responders.
            Therefore and Thusly:
People who could not endure the entire 48 weeks were Non Responders.

Knowing that all the other genotypes only need to endure this toxic medicine for 24 weeks,

Maybe that is One reason they fare better than us 1-A ers,
Who are just getting started at 24 weeks?

My main Point here is this:
    If we 1-A and 1-B people can endure the entire 48 weeks,
Then just maybe our odds of clearing this thing are a little better than reported.

                                    George