Hepatitis Forums
Hepatitis C Main Forums => Hepatitis C Research News & Studies => Topic started by: dragonslayer on March 14, 2015, 11:27:36 pm
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Patients with low levels of quantifiable hepatitis C virus (HCV) RNA at the end of treatment may still have had a successful response to treatment, researchers report in an article published online March 2 in Clinical Infectious Diseases.
http://cid.oxfordjournals.org/content/early/2015/03/02/cid.civ170.abstract
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Paul,
Very encouraging news!
I still am leaning towards a small detected amount after Harvoni may
mean leftover virus that cannot replicate and thus dies off and leaves the body soon after. All these tests do is aggravate and upset us. I really think the 12 and 24 week EOT test is all anyone should get. The others just freak us out if we have a detected show up.
I also noticed that younger people seem to get the 2-4 week UND and older
it takes a little longer. Just an observation.
Good luck to you. I think you are cured and just don't know it for sure yet.
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Hi Paul,
This is interesting research.
I've got my fingers crossed for you!
Best wishes, Mike
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Thanks Mike and Joe,
Yea, the research shows there may be a whole new way to look at the results representing a considerable departure from the Interferon days. Im sure this is even news to the doctors. I wish I knew more about the study, though, and that there were a lot more participants. The fact that all 6 who were detectable at EOT produced SVR12 sounds almost too good to be true.. In the study, actually a higher percentage of the EOT low detectables went on to achieve SVR12 than did those who were UND at EOT... That almost defies logic, although, this is only a universe of 6.. Im surprised Gilead hasnt reported their SVR results on those who reported Detectable at EOT.. But then, as I recall, None of their participants reported Detectable at EOT!
This study, though, is a mystery to me. If anybody knows more, please chime in.. Thanks!
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Can't say I know more that's for sure but hoping it means you and a couple of others aren't done yet and are still in the fight!
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Patients with low levels of quantifiable hepatitis C virus (HCV) RNA at the end of treatment may still have had a successful response to treatment, researchers report in an article published online March 2 in Clinical Infectious Diseases.
http://cid.oxfordjournals.org/content/early/2015/03/02/cid.civ170.abstract
This is amazing and defies logic. I wonder if it is more a result of a false positive in the tests?
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This is amazing and defies logic. I wonder if it is more a result of a false positive in the tests?
I dont think so.. IF you read the study, seems to be more a property of how the DAAs work as opposed to the Interferon protocols... Here's the conclusion reached in the study itself:
"Conclusions. Contrary to past experience with interferon-containing treatments, low levels of quantifiable HCV RNA at EOT do not preclude treatment success."
I take it at face value Pretty unlikely that all 6 who were low level detected at EOT had false positives, and later, running the same tests with the same labs, are SVR.
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I think it could be two-fold: One at the viral DNA level and the changes the antiviral may cause in remaining virus impacting their ability to normally replicate. The other would be at the immune system level, whereby the person's immune system may be able to overcome and kill off any remaining viruses. This could relate to more efficient antibodies within the individual, supercharged by the assistance of the antiviral medications).
This is pure speculation on my part; but it's sure is nice to see that folks who don't completely clear the virus at EOT have a shot at an SVR!
Best wishes, Mike
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@mike, I'm with you on your thoughts about this, i have been stewing about this ever since a few people have been "detected" at EOT. its hard because i kept going back to old treatments and the knowledge that if there was any survivors they would get busy making more "bunnys". But if harvionis method of action is to stop replication, then all the bunny should die. what i would like to know but can't find any info about is what is the virus life span? Like just how long can the bunny live without replication? any thoughts on that? I am also thinking your on target with your own immune system kicking in to help, how could it not be more efficient without the heavy load its been carrying.
kate
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I just received a call from Gilead in regards to a question I posed to them on the Level of Detection (LOD) for their trial tests of <25 IU/mL. LOD for the trials was 9 IU/mL. This means those undetected could have had a VL of 1-8. I now need to see what the LOD is for the test my lab ran for comparison. The gal I spoke with agreed with the results of the small test results that Dragonslayer posted where those showing low levels at the end of treatment can clear it post treatment.
She was also interested in my side effects from the treatment as she does report anything experienced by us and later after it is analyzed will be available in a report. So it would be good for everyone to report your side effects. The more data they have the more complete their analysis will be.
I am feeling good, and sleeping like a baby 20 days post treatment, so I feel very hopeful I am clear and cured and I got my remodel done TODAY! Now my work really begins cleaning & getting things organized, thrown out and donated. It's going to take Spring Housecleaning to a who new level! :D
Katie
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It double posted so I deleted it.
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Am I number 7 who measured low level of detection at EOT and then go on to SVR12? The following news should bode well for the few others who also tested with detected lower levels of viral load at EOT:
Just heard from my doctor regarding the test I did at 7.5 wks post treatment.. As you may recall, at EOT on 1/20/15 I was singing songs of woe because I tested Detected with a VL of 29... The test I just did 7.5 wks post treatment came back still Detected, but with a level below the LLOQ limit of 12.. Doctor tells me if I were relapsing, or if I still had active virus, at 7.5 wks post treatment, the VL would have gone back into the millions where it was before treatment... He thinks that this is a good indicator toward SVR. Ill test again at 12wks, 24wks, and 48wks. But the fact that over a month after stopping Harvoni, the viral load was still decreasing into the range below Lower Level of Quantificationis is certainly a very good sign and that Im most likely in the SVR camp .
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edit- saw your sig.
Here is hoping your are on the road to SVR!
I am guessing that the current thought is that the virus is alive but not able to replicate and has not expired yet?
I am still trying to understand the viral kinetics of this but, here is what I know:
--Harvoni does not kill the virus directly but prohibits its replication
--After a few days on harvoni, it is able to "kill" massive amounts of virus. One person on another forum had a blood test 4 days into harvoni and went from 2 million to 731. This leads me to believe that the half life of the virus is rather short and needs to replicate quickly or most will die.
I am assuming that maybe a few select "super" virus are able to survive long periods and that is what your test is detecting? And that these viruses are effect neutered and then when they die you will get your SVR?
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You stopped tx at 1/20/15? What was the last test?
Here is hoping your are on the road to SVR!
Thanks Charly.. its all in my sig... Started treatment 11/26/14. EOT 1/20/15.. EOT test: Detected with 29. 7.5wk post treatment: Detected < LLOQ which for this test was less than 12. Active virus would have started replicating after EOT and load would have been back in the millions by now.. The fact that the viral load is still dropping 7.5 wks after EOT is an extremely good signal for SVR!
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Thanks dragon, I modified my post and put some questions for you if you can answer them.
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Some interesting articles on HCV stability, die rate, and infectiousness of long lasting HCV.
http://jid.oxfordjournals.org/content/201/12/1859.full
http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1002881
"The median HCV RNA exponential growth rate was 2.2/day, corresponding to a doubling time of 0.31 days (or 7.4 hours). The median peak viral load observed was 3×106 HCV RNA IU/ml and it took a median of 21 days to reach this level. "
"Inactivation of HCV to background levels was detected at 37°C after just 2 days"
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Charly, I dont know if it's 'alive' per se .. These could be dead copies and remnants that are being picked up by the test.. The point is theyre not replicating and from what Ive read, non replicating HCV is dead HCV.... This really delineates the difference between DAAs and older Interferon regimens. From what Ive read, if you were detected at EOT, your virus would begin replicating as soon as treatment ended and in short order, was back to where it was pre treatment or higher... It looks like the HCV community will have to start looking at Harvoni results in a different way... Because of the way it works, low detected amts at EOT are no longer a sign that you didnt completely respond to treatment. BTW, the test used in my lab was the same one used in the article that heads this thread.. its the Abbott m2000 quantitative RT-PCR test.
Also, remember that Gilead in their trials used results of < LLOQ of 25 to signal SVR. So, by most standards, my result of < LLOQ(12) is very likely to become SVR12 in another month when i test again.
Hope this answers some questions.
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Observation:
There is research all over the net that says the virus can live outside the body
for up to 9 weeks. Obviously it doesn't have a host and cannot replicate.
Therefore the same could be true in the body of non-replicable virus.
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Observation:
There is research all over the net that says the virus can live outside the body
for up to 9 weeks. Obviously it doesn't have a host and cannot replicate.
Therefore the same could be true in the body of non-replicable virus.
Interesting.. so, because its not replicating, even if its alive now, its of no consequence? I presume, after awhile, it will die off... however, when its living outside the body, there is no natural immune system attacking it.. Isnt it possible that under that influence, in the body, its no longer alive and has only 'remnant' status, detectable but inconsequential?
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That's what I am thinking. I'm sure in the near future some lab will study that once
they see what's happening in the real world. It's too bad we all have to stress about
these things. I imagine a test will come out in the future that determines replicable vs non-replicable virus on a detected result soon. That test would ease all of our minds.
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Paul,
In 3 weeks I am scheduled for my 12 week post test.
My doctor wrote me an order for a Qualitative test that just shows positive or negative with no viral load numbers. I am going to demand the Quantitative VL test in light of your findings. Thank you.
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Observation:
There is research all over the net that says the virus can live outside the body
for up to 9 weeks. Obviously it doesn't have a host and cannot replicate.
Therefore the same could be true in the body of non-replicable virus.
The half life of the virus is highly dependent on temperature. Look at the links I posted above. At low temps the virus can live over 6 months. At 37 deg. C or (body temp) the half life is about 2 days.
This makes sense since some people go undetected at 2 weeks. (I did!). If there are still viruses that remain at detected levels 7.5 weeks after tx, assuming the body takes 1 week to clear the meds, then these viruses appear to be abnormal.
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Paul,
In 3 weeks I am scheduled for my 12 week post test.
My doctor wrote me an order for a Qualitative test that just shows positive or negative with no viral load numbers. I am going to demand the Quantitative VL test in light of your findings. Thank you.
Hi Joe, I think that's a good idea.. I know the Qual tests are supposed to be more sensitive. But as we've seen simply detecting it is not enough with Harvoni, and can be misleading. Further, all tests, both quant and qual have LLOD values. At some level, its not detectable and will report as UND even though we know there is still some virus present but of no consequence. These LLOD values, therefore, in the grand scheme, must be seen as somewhat arbitrary, since there will always be some virus present beneath the LLOD value. Even consider this.. Lets take a test that has an LLOQ value of 12, and an LLOD value of 7. If you have a real value of 6, youll report UND, but in reality, is that really a better result than, say, 10 which will report Detected < LLOQ?
Therefore, At these levels and with Harvoni, the results reported seem somewhat arbitrary and without consequence.
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Paul...That is GREAT news and so encouraging! I am doing a Happy Dance for you! I have a PT appointment so need to get going but will post more later on this subject.
We need to remember a virus isn't really "alive" as we tend to think of life. It is basically a very specific strand of RNA that can only replicate in a liver cell. It is more like a seed, floating through the blood stream and needs a liver cell to become viable and replicate and I am sure different environments give it a different time frame of being viable.. They are like other worldly aliens!
Have a great day and do something good for yourself!
Katie
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There is a line of research (relating to late relapsers) that suggests viral fitness and replication capacity may be a factor. The theory is that within the pool of HCV virus present in a patient, a low number of these virus may have structural deficits impacting replication. Since direct acting antivirals, such as Harvoni, target HCV replication, unfit viruses may not responded to the antivirals the way a healthy virus would. Thus:
"An antiviral might lead to a substantial fitness cost to a virus, which means that only very unfit virus might be able to resist elimination, which in turn requires the mutated or selected unfit virus to revert to higher replicative capacity, which might take several months or years."
Stated differently, the unfit virus may continue to survive (in small numbers) and mutate, at a later date, to the point of normal HCV replication, which would continue the infection.
Mike
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I don't like that thought, Mike.
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Stated differently, the unfit virus may continue to survive (in small numbers) and mutate, at a later date, to the point of normal HCV replication, which would continue the infection.
Mike
I am not sure how mutation can occur without replication. Traditionally the mutation occurs during the replication. I would think that if there are "unfit" super long lasting strands that are incapable of replicating that they would also be incapable of mutating back to being able to replicate.
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>>"An antiviral might lead to a substantial fitness cost to a virus, which means that only very unfit virus might be able to resist elimination, which in turn requires the mutated or selected unfit virus to revert to higher replicative capacity, which might take several months or years." <<
Wait... What? Really? So then, what about those predictive SVR values for 4 wks and 12? IF SVR4 is 98.5% predictive of SVR12 and SVR24, and SVR12 is 99.8% predictive of SVR, then where is it that these 'late relapsers' show up? Are we talking bout the 1.5% where SVR4 turns out Not to be predictive, or the .2% of the SVR12?
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The theory is that the 'unfit' virus do not replicate as efficiently or exactly like a fit virus, and, thus the antivirals may not be able to shut down/target the specific proteins needed for replication the way they do in a 'fit' virus.
Since an unfit virus may still replicate, in theory, it could evolve to a more efficient/fit copy (mutate). If this occurs (evolving from unfit to fit), the infection continues or resurfaces.
Mike
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The theory is that the 'unfit' virus do not replicate as efficiently or exactly like a fit virus, and, thus the antivirals may not be able to shut down/target the specific proteins needed for replication the way they do in a 'fit' virus.
Since an unfit virus may still replicate, in theory, it could evolve to a more efficient/fit copy (mutate). If this occurs (evolving from unfit to fit), the infection continues or resurfaces.
Mike
So, then, even with Harvoni, being declared SVR12 and SVR24 is not a guarantee that you're finally cleared of the virus? I thought those proclamations were pretty good, and that once they were achieved, you should consider yourself 'cured'. Does this research to which you refer change this?
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The theory is that the 'unfit' virus do not replicate as efficiently or exactly like a fit virus, and, thus the antivirals may not be able to shut down/target the specific proteins needed for replication the way they do in a 'fit' virus.
Since an unfit virus may still replicate, in theory, it could evolve to a more efficient/fit copy (mutate). If this occurs (evolving from unfit to fit), the infection continues or resurfaces.
Mike
Thanks for your imput Mike, this is very interesting stuff and since Harvoni is so new there may be unanticipated issues like possibly SVR12 & 24 not being as reliable.
Mike, Do you have any links to this literature?
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Late relapse does occur in a small number of folks who have been virus free (SVR24+). Most have been attributed to reinfection - but not all - which has been confirmed through DNA analysis of the original virus present prior to treatment, and analysis of the DNA of the virus that reappears months or years later.
There are two schools of thought as to why this occurs: The unfit-to-fit viral mutation theory and the reservoir theory (that is, that the HCV virus jumps the blood-brain barrier and establishes a pool/reservoir within brain tissue or within the CNS that the antivirals cannot penetrate).
Both these theories are currently being studied. Again, late relapse is rare, though this research may be able to answer some of the reasons why initial treatment fails.
Mike
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Found a good link on the subject:
http://jid.oxfordjournals.org/content/early/2013/11/14/infdis.jit543.full
A very interesting read. Yes these direct antivirals seem to be changing the game.
some excerpts:
"""For most patients with relapse, onset of relapse occurs within the first 12 weeks, although relapse in a minority begins between weeks 12 and 24 [4]. The importance of monitoring beyond week 24 was highlighted in one study using direct antiviral therapy that reported late relapse in a patient at week 36 [5]; this patient thus achieved a SVR24 but not a SVR36."""
Paul, I wonder if the study you quoted when they said the 6 patients went on to achieve SVR12 whether they were <15 detected, but according to current protocol is considered SVR when they may just be late relapsers.
"""One attractive option for such a reservoir is the brain. There are several lines of evidence suggesting involvement of the brain in HCV infection [12], such as the high frequency of depression during interferon-based therapies in patients with HCV infection [13, 14], compared with a frequency of depression of <6% among patients with hepatitis B treated with the same regimen"""
Could depression be an indicator that HCV has crossed the brain barrier??
"With new direct antivirals against HCV currently not being assessed for their ability to cross the blood brain barrier, more late relapses might emerge in the future. However, clearance of the major viral pool might also allow a patient's immune system to control the remaining viral pools."
I would think that maintaining a healthy lifestyle before during and after treatment is more beneficial if you possibly need your immune system to control the remaining viral pools.
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Found a good link on the subject:
http://jid.oxfordjournals.org/content/early/2013/11/14/infdis.jit543.full
A very interesting read. Yes these direct antivirals seem to be changing the game.
That looks like the research to which Mike was referring.. Kind of depressing.. Looks like we have to stay vigilant for a long time... One thing I dont get is, if the virus is really gone, then why does the health of the liver get worse over time?
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One thing I dont get is, if the virus is really gone, then why does the health of the liver get worse over time?
I did not read that in the literature? I would think that the liver would do well due the limited replication of the virus during its "hibernation" when it mutates out of the unfit state and replicates again is when it will revert to straining the liver.
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I did not read that in the literature? I would think that the liver would do well due the limited replication of the virus during its "hibernation" when it mutates out of the unfit state and replicates again is when it will revert to straining the liver.
Read:
"A recent long-term analysis found that only about 50% of cirrhotic patients experienced in reversal of cirrhosis after achieving a SVR, while a significant number of patients achieving SVR in the absence of cirrhosis still progressed to cirrhosis despite being cured of HCV infection "
found in http://jid.oxfordjournals.org/content/early/2013/11/14/infdis.jit543.full#ref-20
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Read:
"A recent long-term analysis found that only about 50% of cirrhotic patients experienced in reversal of cirrhosis after achieving a SVR, while a significant number of patients achieving SVR in the absence of cirrhosis still progressed to cirrhosis despite being cured of HCV infection "
found in http://jid.oxfordjournals.org/content/early/2013/11/14/infdis.jit543.full#ref-20
I think this is an aside from the main part of the article. Other more recent research shows that people that achieve SVR mostly live the same lifespan as those that never had HCV.
http://www.hepmag.com/articles/life_expectancy_2501_26464.shtml
I thought you were wondering if during the delayed relapse period the liver would still deteriorate. I am not sure but could assume that the liver would not be damaged during this time because the damage happens during the replication.
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I think this is an aside from the main part of the article. Other more recent research shows that people that achieve SVR mostly live the same lifespan as those that never had HCV.
http://www.hepmag.com/articles/life_expectancy_2501_26464.shtml
I thought you were wondering if during the delayed relapse period the liver would still deteriorate. I am not sure but could assume that the liver would not be damaged during this time because the damage happens during the replication.
Hi Charly.. thanks for posting that.. I must say, this morning, when my dr. called and gave me the news on my recent test, my spirits soared. .Then, after reading of the research which Mike posted relative to late relapsers and the theories behind it, I started sinking ... Then reading about non cirrhotic patients still progressing toward cirrhosis even after SVR was pretty much the coup de grace.. Im being a bit melodramatic here, and I still am thrilled with the < LLOQ result, even though its detected... But this disease is so rotten with the tricks it pulls, its hard to be thoroughly optimistic with all the gotchas it's occasionally wont to present!
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Hi Paul,
I didn't mean to bum you out. I was only trying to explain why a small viral load might linger after treatment.
I would note that late relapse is not common and the occurrence is very rare. The research I mentioned are theories and not conclusive, relating to late relapse and not specific to your situation.
In addition, the research on progression to cirrhosis is mixed and I've read studies that suggest the exact opposite. I think it's fair to say that once the virus is cleared, the liver can then begin the healing process and can actually rejuvenate at the cellular level. There is no question that overall liver function improves in most patients.
This is the golden age for HCV treatment and we will all be cured in the very near future!
Best wishes, Mike
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Oh Man.. Thank you, Mike... Youve just lifted the pall I had managed to caste over myself! Thanks for putting the research in perspective. Feeling better already.. Seriously.. Thank you Thank you.
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Hey guys....We can't be jumping to conclusions when different theories appear especially since we do not have all the information or have difficulty understanding everything that is available. Stress is not good and we need to concentrate on the positive.
Who is to say if there are unfit virus, that they can even replicate at all? There isn't enough information out there and our group is going to add much more information. These are just theories and many theories are posed just to try and figure out an unknown...such as why some, even if very few, relapse or do not clear.
As far as the liver goes, it will rejuvenate itself once it is no longer under attack, however the scarring from cirrhosis may not do as well and remember, as we age all of the damage to any part of the body seems to amplify as our systems just don't recover as well. Those with cirrhosis or high level scarring are still going to deal with that damage and a liver that is not doing it's job 100%. They need to do all they can to protect their liver and I certainly plan on that even though my liver is in good shape.
I contribute my liver to doing as well as it is because I was very particular on everything after the diagnosis, and would question the doctor and pharmacist on prescribed medication and over the counter as well to make sure I was taking only things that had minimum or no impact on my liver.
A friend of mine had HepC GT 2 and was cured at least 10 years ago with a long difficult treatment. She is still tested for HCV annually and has remained clear but now has cirrhosis, so her liver disease has progressed. She has a low pain tolerance, takes handfuls of OTC meds, even gets anesthetized for root canals, and I contribute all of that to the condition of her liver. She doesn't do alcohol and eats healthy but is a pill popper, like so many of us Americans. I always figured, pain is there for a reason and sometimes learning how to deal with it instead of always medicating is better. At least I know if or when I have a serious condition, I can take antibiotics or pain medication, knowing I haven't overdone it for minor things which I could deal with.
Sorry for that rant, but I am delighted with the news of people clearing after a low level at EOT and am going with that. Like I said, I am feeling too good to be sick, and if I continue to feel this good I know I can last another 25 years or so even if I have HCV, so I am a happy camper right now and plan to be around a long time!
Spring is coming and it will help all of us have a better more positive perspective. It is the season of rejuvenation!
Katie
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Dragonslayer
You've been on the rollercoaster long enough for 1 day. Lol
You're gonna clear the beast.
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Just to add my 2 cents about liver recovery in light of viral eradication in the presence of cirrhosis I think it could depend on the severity of the cirrhosis in the patient at SVR. That a patient with more advanced cirrhosis maybe already on the downhill slide and also other factors like say high BMI and thus fatty liver could come into play as factors as well.
Hope for the best is all we can do. And even if worst case we do still need a transplant at least we wont have hep c to attack the new healthy liver if we have to go down that road.
Paul Hoping you results are an indication of good things to come!
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Good morning everyone,
WOW, what a roller coaster of emotions! Sam, you hit it on the head :) I just read this topic from start to finish - hope, joy, confusion, despair and back again!! Thanks to everyone who participated and especially to Mike, Paul, Katie and Lynne. Much to think about. @Charly8, thanks for all the links, etc, I'll have to get back and study these when I have more time.
I go for my one month post 12 wk Harvoni next Wednesday and have not been feeling as well as I did, so I'm feeling apprehensive about it. These posts are a bit scary, but also reassuring. As Katie and Lynne stress,we have to stay positive, hope for the best. A step, and a few deep breaths, at a time. Hoping for the best for all of us! ....Islandgirl 8)
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Regarding the study referenced in the opening post in this thread, I have a bit more info.. I contacted one of the key medical staff who worked on this research, and here is an excerpt from her reply:
"The study referred to in our recent publication in CID is the treatment of 60 patients with sofosbuvir and ledipasvir with or without GS-9669 or GS-9451 for 12 or 6 weeks. This study was conducted at the NIH independently of Gilead. The results of this study were recently published in the Lancet (http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2961228-9/abstract). Given the six patients with low levels of quantifiable virus at EOT (14-64 IU/mL) on the six-week regimens, our results suggest that detectable viremia at EOT does not signify treatment failure and I believe this will come up in the real-world. Your EOT viral load of 29 IU/mL falls within this range and I definitely would not count yourself as a treatment failure without the final SVR12 results. I should say, however, that we did not have many treatment failures in this study (1/60). It is simply difficult to predict treatment response with these low levels of viremia at EOT."
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Thanks Paul! With your current decrease, I am positive your will reach SVR12 and it is such positive information for all of us!
Katie
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Thanks Paul! With your current decrease, I am positive your will reach SVR12 and it is such positive information for all of us!
Katie
Thanks Katie.. I did want to mention another testing anomaly that I found in one of Mike's references. In one of the studies, it was found that roughly 1/3 of the patients that tested Detected but < LLOQ(12) in the Abbott real time Assay that we used, tested 'Target Not Detected' using the Cobas TaqMan test! Just to muddy the waters a little more.
This can be found in: http://www.biomedcentral.com/1471-2334/14/S5/S8 in the section entitled: Differences between HCV RNA assays with DAA therapies
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I guess that is why we test at 12 weeks post treatment because we apparently cannot determine at EOT whether the virus is eridicated or not I guess the scientific method does have limits certain things cannot ever be determined.
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I guess that is why we test at 12 weeks post treatment because we apparently cannot determine at EOT whether the virus is eridicated or not I guess the scientific method does have limits certain things cannot ever be determined.
Those members who have been excoriating doctors for not doing Harvoni on treatment or EOT testing, take note!
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Very true, but they should explain things instead of leaving people hanging. I would much prefer to see I am a strong responder than to wait with so many questions and stress out. Many doctors, such as mine who is a GP and specializes in internal medicine, is so busy I know he doesn't have time to catch up on every little bit of information but he does the best he can and I trust him. I am grateful he tested me at 4 weeks & EOT because I would be climbing the walls by now.
Hopefully in the future Gilead and treating physicians will have a more complete FAct sheet explaining the suggested treatment and tests and expected results. Since we were basically the first group, we didn't have adequate information and it is understandable. Because of this we investigated for ourselves and if nothing else, it allows me to feel I have some control over my treatment even if it is just in understanding it.
I am very grateful to you, Dragonslayer and Mike and Lynn and everyone who takes time to do research and share.
Enjoy this glorious weekend! It is so beautiful here with the sun shining and spring bursting all over!
Katie
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>> Because of this we investigated for ourselves and if nothing else, it allows me to feel I have some control over my treatment even if it is just in understanding it.<<
The problem is that when we investigated for ourselves, much of what we came across was information that pertained to the Interferon treatment regimens, which, it turns out, doesnt apply in full to the interferon free treatments.. Much having to do with the response-guided-treatment recommendations attendant to Interferon doesnt really apply well to the DAA model. The testing has changed, the tests themselves need to change, and the treatment, as Mike astutely pointed out, is outpacing the abilities of the tests. We are indeed the first real worlders and a ton of crucial info will be gleaned from our results and our experiences.
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And I did take that into account, Paul. I started this thing by questioning what the tests actually meant and different tests with different sensitivities and how that could impact what results were reported. I feel that was a worthwhile course to question.
All in all it led to you finding out:
"The study referred to in our recent publication in CID is the treatment of 60 patients with sofosbuvir and ledipasvir with or without GS-9669 or GS-9451 for 12 or 6 weeks. This study was conducted at the NIH independently of Gilead. The results of this study were recently published in the Lancet (http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2961228-9/abstract). Given the six patients with low levels of quantifiable virus at EOT (14-64 IU/mL) on the six-week regimens, our results suggest that detectable viremia at EOT does not signify treatment failure and I believe this will come up in the real-world. Your EOT viral load of 29 IU/mL falls within this range and I definitely would not count yourself as a treatment failure without the final SVR12 results. I should say, however, that we did not have many treatment failures in this study (1/60). It is simply difficult to predict treatment response with these low levels of viremia at EOT."
which is VERY good news for you and I and others who may come back positive for the viral load. We just have to keep things in perspective and I will always search out information to help give me understanding or fix a problem.
EX: the carpenter left a gap in the top of my door casing. Stuff like that drives me crazy so I decided to fix it and tore off the trim thinking I could shim the top down for a tight fit. Turns out he had 2 thin brads bent over on the door jam and left them instead of pulling them out so the casing wouldn't seat properly. That made my easy fix a big tear out everything and start over. HA! Typical, but it is fixed and how I expect things to be done. With my arthritic hands I was trying to be good to myself and pay money to have stuff done, but fixing stuff is always more work than doing it right, yourself, the first time.
So Paul, take a deep breath and do something good for yourself. We are on the road to recovery and the info you provided is valid and made a difference in my outlook. Thank you!
Katie
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Katie and Paul - A BIG THANK YOU to you both!
Katie, I'm glad you got your project just how you want it and that it's beautiful Springtime there :) I know it's truly breathtaking! BTW, I just found your pm to me and will try to figure out how to post the pictures when I can get to it. Sorry I didn't see your message sooner.
Hugs, and positive healing energy, ....Islandgirl 8)
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Very informative troops,
I commend you all, now, give me 10 push ups and hold the phone,
Your answer is coming! J/k.
We shall be free!!!!!
Laugh, it's good for Ya!
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That's a good one Bubba! I needed that!
;)
Katie
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I agree! I needed it too.
Gloomy, rainy day here and I developed a full mouth irritation of some sort just in time for my dental appointment today :-\
My 1 month post 12 wk EOT labs on Wednesday as well as labs for something called Petechiae or ecchymoses to see what's going on with the tiny spots that look like blood that I've been getting off and on - plus skin breaking too easily from a scrape and bleeding too easily. No, I'm not on blood thinners. My doc thinks it's probably nothing to worry about, but it's possible I'll be referred to a blood specialist if it's not what she's expecting.
I'm too damn tired for those push ups, Bubba, but I do plan to go to my "Solid Gold" fitness on Wednesday and do what I can. The music is so upbeat and fun that I know it will help my week! Focusing on laughter and spring flowers and being free! ....Islandgirl
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I wrote a blog on this - hope it is helpful: http://blogs.hepmag.com/lucindakporter/2015/03/new_hepatitis_c_trea_2.html (http://blogs.hepmag.com/lucindakporter/2015/03/new_hepatitis_c_trea_2.html)
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Thank you Lucinda! Good information, easily understood and keeps me hopeful!
Katie
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Hi Island Girl. I've been wondering how you are doing! Sorry you have something else to deal with. Is you sinus infection gone? I remember you taking OTC meds along with spray and they can actually cause this as they act like blood thinners. I hope you no longer need them for your sinuses and that things will settle down for you! Good luck at the doctor's office and with your tests.
Be well and keep us posted! We are on our way to a fantastic, healthy summer, so I am sending you healing, colorful sunlight and energy!
{{{HUGS}}}
Katie
hugs work wonders too!
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Ditto! Great article, Lucinda!
I've bookmarked it for those times I'm feeling apprehensive - just to give myself a boost of reassurance :)
@Katie, thanks. Still have some sinus issues and trying to take less medicine/spray as I'm not sure they are helping anyway. Maybe more harm than good. I really thought I'd be feeling better than I do by now - not sleeping as well as when I was on Harvoni either. Just trying to stay positive and take it as it comes. Thanks so much for your comments and your wonderful positive attitude! BIG HUGS back
...Islandgirl 8)
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STILL UNDETECTED @ 1 MONTH POST 12 WK HARVONI TX!!!!!!!!!!! (also posted at another site)
Good morning everyone, and welcome to all our new Forum Family members too! Thanks also for everyone's encouragement while I've been feeling so cr*%*y, Meg and Katie I couldn't do without you guys! Physically I'm still not feeling great but emotionally - WOW such good news! I was really frightened that I'd relapsed or something.
This morning I called the lab and found my results were in so went over and picked up copies - couldn't wait until next week
The Hep C viral load tests both still show me as NOT DETECTED! Fantastic news!!!!!!!!!!!!
However, the other test re my blood work will need to be explained by the doc. Most things looked within normal limits, but my platelet count is 124 which is abnormally low (140 to 400 range is where it should fall) That may explain why I have easily exhausted energy...
Also, something called Eosinophil is abnormally high at 6 (normal range is 0 to 5 - so need to find out what that's about. It's possible that these could be the aftermath of the Harvoni that destroyed the Hep C virus???? Anyway, the HCV is still undetected and I now anticipate it still being undetected in September - at which time I can say CURED!!
Hugs and healing energy for all of us! ....Islandgirl
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Hi Islandgirl,
Congrats! That's great news.
Eosinophil are white blood cells that our bodies produce to fight inflammation and allergies:
"Eosinophilic functions include: movement to inflamed areas, trapping substances, killing cells, antiparasitic and bactericidal activity, participating in immediate allergic reactions, and modulating inflammatory responses."
I would imagine these will normalize and were a by-product of treatment.
Again, CONGRATS on the SVR4! Looks like another dragon is slayed!
Best wishes, Mike
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Big happy smile here, Mike!
Thanks so much for your explanation and comments. Do you think the low platelets are also a by-product and will normalize too?
Thanks for letting me pick your brain :)
.....Happy Islandgirl 8)
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Yes. I would imagine the platelets will normalizes, as well. Rember, these medications are powerful and our bodies had to adjust to the meds, and now have to adjust to not being on them, as well as not having to deal with the HCV!
Make sure you talk with your doctor about these at your follow up.
Best wishes, Islandgirl!! You cleared the virus! ♪♫ :)
Mike
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Thanks, Mike. I really appreciate you helping put a smile back on my face. :)
I have an appt to discuss all this with my doc soon, just needed a little input beforehand. I love my doc but much of the time they are learning with us. I'm the first patient she was able to get approved for Harvoni and I think I got my approval just before the insurance companies really started holding back approvals. She feels I have cleared the virus too. I just got scared that maybe I hadn't since I wasn't feeling as good as I did while on treatment.
Time for a big breath and to let myself believe and enjoy :) ...Islandgirl 8)
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Hi island girl
Yay SVR 4 great news!
How is your liver do you know?
My platelets have been about 90 for several years they started to fall a couple of years after I was diagnosed with cirrhosis. But I guess it could be an effect of the meds too your doctor should know more than us.
Congrats again!!!!
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Thanks, Lynne!
My last several sonograms have been fine, as was the biopsy I had some years ago, but I'm thinking to ask my doc about having a Fibrosure test or Fibroscan (not sure there is a Fibroscan anywhere in my area) just to be sure.
The insurance co required an updated sonogram prior to approving my treatment and it was good. My doc has not seemed concerned with my platelets, but we'll be discussing it soon.
I can't remember if wished you a Happy Birthday, but I hope it was. I wish you all the best and appreciate your knowledge and support.
We have the BEST moderators!!!!!!!!!!!! Thank you, ....Islandgirl 8)
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What I am still trying to figure out and none of the tests clearly show is the following:
When they say in these studies that you are SVR12, they only state <15ul. It does not state if you are <15ul detected or undetected.
For example for Gilead's studies the definition of SVR12 was only <15ul. (not <15ul undetected)
This means that according the this definition of SVR12 you could also be <15ul detected and they would consider that SVR12.
This leads us to the following question: Is SVR12 <15ul detected truly SVR? or are we in a different paradigm that the virus sits dormant and could re-populate at a later date and therefore SVR12 means less than it used to.
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Hi Charly, It is confusing. Wish I had a spreadsheet as I get lost with the different tests and the results along with timelines as there are different ones out there.
Just remember we are really the first group and they will learn from our results. I am just hopeful since there are those that cleared even though they were still detected at the end of treatment.
If you haven't already, just read the posts on this forum from top to bottom as when we first heard about this, we went through the same questions and confusion and research as you are. Dragonslayer was really thorough to the point of all of us getting a bit stressed out. There are no concrete answers and the trial results certainly do not cover everything we are.
We just have to wait and see, as difficult as that may be. April 20th can't come fast enough for me so I know what to do next. Since you are waiting for results, I wouldn't get all worked up until you find out where you are. Most everyone comes back UD which is wonderful!
The virus can't sit dormant and then pop up again down the road...say in 2 years, or even 1 year. It needs to replicate to stay viable. If there are a few, hiding out, you could have it come back and that is the purpose of follow up tests at post 12 and 24 weeks. They figure if it hasn't shown back up at that time, you are cured as they have passed the phase where they can replicate.
Katie
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The virus can't sit dormant and then pop up again down the road...say in 2 years, or even 1 year. It needs to replicate to stay viable. If there are a few, hiding out, you could have it come back and that is the purpose of follow up tests at post 12 and 24 weeks. They figure if it hasn't shown back up at that time, you are cured as they have passed the phase where they can replicate.
Katie
Unfortunately Katie the direct virals may be changing this assumption. Their affect in some case may do just that. See here:
http://jid.oxfordjournals.org/content/early/2013/11/14/infdis.jit543.full
some excerpts:
"""For most patients with relapse, onset of relapse occurs within the first 12 weeks, although relapse in a minority begins between weeks 12 and 24 [4]. The importance of monitoring beyond week 24 was highlighted in one study using direct antiviral therapy that reported late relapse in a patient at week 36 [5]; this patient thus achieved a SVR24 but not a SVR36."""
"""The second factor relates to the potential of late relapsing virus deriving from a reservoir. There is potential compartmentalization of HCV variants with reduced fitness, allowing for delayed relapse. Because interferon is not known to induce mutated unfit virus, it is most likely that late relapse of infection in patients who received interferon/ribavirin-based therapies involves virus from extrahepatic reservoirs, which might offer protection from the antiviral activity of drugs, or alternatively, that the harbored virus might have an intrinsically low replicative activity, making it less vulnerable to antiviral pharmaceuticals.
One attractive option for such a reservoir is the brain. There are several lines of evidence suggesting involvement of the brain in HCV infection [12], such as the high frequency of depression during interferon-based therapies in patients with HCV infection [13, 14], compared with a frequency of depression of <6% among patients with hepatitis B treated with the same regimen"""
"With new direct antivirals against HCV currently not being assessed for their ability to cross the blood brain barrier, more late relapses might emerge in the future. However, clearance of the major viral pool might also allow a patient's immune system to control the remaining viral pools."
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True Charly and there will always be exceptions as there are so many variables as each person's medical history and life style is different. This was talking about the old treatment as well, but it is concerning that they began replicating again. The thing is, the tests have become more sensitive as well, so perhaps they really weren't UD but unable to detect a small number. I see the report was published in 2013, however the actual data may very well be several years old. I haven't read the report yet, just what you posted but I will. Thanks for doing that.
I'll also see if Gilead has done some long term followup with their Harvoni trials.
We will always follow up with a yearly test. A friend of mine had GT 2 and was cured 10 years ago. She has blood work done annually and has remained clear, but her liver damage has progressed.
I always try to stay positive and will continue to do so. It is healthier.
Enjoy your day!
Katie
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Late relapse happens in a very small percentage of patients who have achieved an SVR24 <.001%, and is not well understood.
The good news is that it is very rare. The bad news is, if HCV 'hides' in the small reservoirs, this would make it more pernicious than thought.
Unlike HCV, the HIV virus is known to 'hide' which is why it cannot be entirely eradicated, meaning that those infected must take antivirals for life, in order to keep the virus in check.
The research is consistent that this is not the case with HCV, at least for the vast majority (99.99%) who clear the virus with a confirmed SVR24.
Still,a small number of those who cleared the virus have had it reemerge months (and even years) after a confirmed SVR24.
Some of these may be due to reinfection, though others have been confirmed (via DNA analysis) to be identical to the original viral infection, suggesting a true relapse cf. reinfection.
Because of this several theories have emerged: The reservoir theory; the fit-unfit virus theory; and a unidentified viral sub-type and/or mutation theory.
Please note, however, that theories are 'best guesses' - not fact - and much more research needs to conducted on this very rare, small population known as late relapsers.
Best wishes, Mike
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Thanks for the clarification Mike! You are so appreciated!
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What I am still trying to figure out and none of the tests clearly show is the following:
When they say in these studies that you are SVR12, they only state <15ul. It does not state if you are <15ul detected or undetected.
For example for Gilead's studies the definition of SVR12 was only <15ul. (not <15ul undetected)
This means that according the this definition of SVR12 you could also be <15ul detected and they would consider that SVR12.
This leads us to the following question: Is SVR12 <15ul detected truly SVR? or are we in a different paradigm that the virus sits dormant and could re-populate at a later date and therefore SVR12 means less than it used to.
That really is a good question; one which Ive been mulling over.. It would be good to know if you really can be Detected and Less than quantifiable 12wks post treatment... How would the virus be able to exist for 12 wks without replicating? Isnt replication required for its survival? As you probably know, I tested Detected, < LLOQ(12) at 7 wks... my SVR12 check just came back UND, or so the doctor told me via phone; I want to see it for myself.. But your question is still a good one.
BTW, The Gilead marker for SVR was 25, not 15 according to the documents. And yea, they do not say if it was UND <25 which they used, or Detected < 25, which also is confusing since I believe they used the Cobas TaqMan v2 assay, which so far as I know, has an LLOQ value of 15, not 25!
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OMG Paul.....you got the UD result!!!!I am cheering you on and SO happy!
Did you read what Mike posted. That clarified a lot for me and should answer some of your questions. I think the different tests also have brought about some confusion, but like I said, everyone is different depending on medical history and life style and there always will be exceptions. The <0.001 on late replication is encouraging though.
I found the brain barrier thing interesting as I hadn't heard that before. I wonder if that was what was happening to me during week 8 and 9 when I went from such a "high" to such a horrible low. If so, hopefully it was Harvoini knocking it out since I popped right back.
Congratulations again, Paul. :D 8) You definitely have the alien parasite defeated and are the DRAGONSLAYER! >:(
Katie
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Paul!!!!!!! Congrats! ♪♫
https://youtu.be/DhlPAj38rHc
Best wishes, Mike
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Awesome Paul, that is great news!!
Congrats!
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Paul!!!!!!! Congrats! ♪♫
https://youtu.be/DhlPAj38rHc
Best wishes, Mike
Ha! Thanks Mike, and all. I hope, and expect that Rocky theme song to get LOADS of play in the next few wks and mos, as the SVRs start rollin' in.
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Paul,
I'm so happy for you. If I could play the horn, I'd be blowing that song all day long - so loud - that you'd be able to hear it from Toledo, Ohio! 8)
Best wishes on your new life, Mike
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Mike, Katie, Charly, and all... I cant thank you enough for your support and encouragement. Sometimes, good stuff really does happen!!! SVR for all! And thanks for all the research posted on these pages. Without some of the encouraging study results regarding EOT detectable labs, it would have really been a much tougher slog.
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Wow Paul that is wonderful, fantastic, awesome, incredible, and running out of words NEWS!!!!!!
Like they say it ain't over
And now they are playing the rocky theme song!
Congratulations !
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Time for my happy dance everyone!!!!
I have an appointment on the 27th to go over my test results but about 5 minuets ago, the doctor's office called with my UNDETECTED RESULTS SO I COULD HAVE A GOOD WEEKEND. The nurse practitioner was as excited as I am. I sent the current article posted a couple days ago and she said she read it and found the news on the EOT results wonderful and amazing!
Thanks for all of your support. I am still having a difficult time processing this AND DON'T KNOW WHAT TO DO WITH MYSELF! Another DRAGON dies AND I AM NO LONGER A BIO-HAZARD!!
From a very happy Katie!
A little history for those not familiar with my treatment.
Diagnosed 2005
68 years old
no idea how I became ionfected
GT 1a
VL for last 10 years fluctuated from ~3million to 16 million
Hep C symptoms: horrible fatigue, insomnia, brain fog and confusion, poor skin quality, dental issues.
VL begin of treatment 2.6 million
4week = 59
EOT = <12
8 weeks post treatment UNDETECTED
ALT/AST have been in normal range for 95% of time since diagnose
Treatment was easy for me and I felt better than I have in years, even a bit hyper.
Since stopping Harvoni I am very tired (not the severe fatigue) but all other HepC symptoms are gone and even my dental checkup last week was improved with very little scraping needed for the cleaning.
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Woot Woot!
So happy for you Katie! ♪♫
Enjoy your new life!
Best wishes, Mike
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Katie and Paul! Doin' that Happy Dance and feeling the JOY!!!! I'm so happy for you both :)
Katie, we've been there for each other through some pretty rough times and I'm so overwhelmed by your good news that I hardly know how to put how I feel into actual words. Thanks for helping pull me through and for the honor of sharing your good news! Yes, a very happy weekend in store!
Love and blessings to all our Harvoni family! ....Islandgirl 8)
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Isn't this just wonderful!!!!!!!!!!!!!! Congratulations.
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Fantastic news Katie !!!!!!!
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Katie, good job taking care of those mini beasts.
Enjoy!
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Thanks everyone. I'll still be checking in to give support and see how my fellow warriors are doing. You all have helped me through this more than you know!
Katie
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Um I was falling apart yesterday and this just found thread has saved my sanity.
Thank you to all.
Kim
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Hi all, keep in mind that EASL conference is going on right now and I am sure this topic of VL/EOT/when to test will be discussed, so watch for info on the presentations when they come out in the next couple of weeks. Still lots to learn about this beast. FT
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Hi Kim, you hang in there and try not to stress out. I am a biologist and dealt with viruses in microbiology and I think (just my opinion) that the test sensitivity is picking up fragments of protein in the blood from the virus when it is still detecting the HCV but not able to calibrate the number (< 12 or <15). The virus duplicates exponentially and if it was still viable it would show up. Now I know it has a cycle for replicating, and I believe that is why testing occurs at 4 or 8 week intervals.
Let us know how your next test come back and I have this feeling you will beat this beast. I had a test again this past week since it has been over a year since I completed treatment and my last test was in August. I want to be absolutely sure as I figure there are always rare, weird circumstances that can pop up but I am not the least bit nervous about it. It is more for my other health care providers who aren't informed on this virus, such as my dentist. I hate it when they say "you're in remission". NO, I am cured. I can assure you, he and others (even lab techs) are getting an education from me. HA!
You are always welcome to ask any questions and you are not alone. Glad you found this forum.
Take care and have a great weekend!
Katie
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Hi Katie,
Thank you very much for your kind reply. I mentioned in another post that I have taken screenshots of yours and Dragonslayer's stats to refer back to for mind control support. 8)
It seems that I am linking all sorts of physical manifestations to my relapse paranoia. For example, I felt a pang or more in my right side recently and then my urine was dark and away went my mind. After some water, my urine was normal. It was in the morning after a couple of capucinnos (sp) but that with a slight right quadrant pain really set me off. Now I should mention that I really never had symptoms or I didn't notice them if I did. I was an excellent ostrich so may have ignored any little symptoms in any event.
One thing discovered when I had an ultrasound was that I have a hemangioma on my liver, however, was advised that it is not related to hcv, nor is it cancerous and is often referred to as "birthmark". This could explain right quadrant jabs I suppose.
I have indicated to my GP that I have been quite stressed about waiting 3 months for another viral load so he said I could go for another one if I like. Yes I would like and will go for one today! I finished treatment on March 16 so this will be about a 5 week viral load test which should give me a good idea of whether I am progressing or heading towards relapsing. If I am going to have to deal with relapse possibilities, I will need to prepare mentally sooner than later.
I was one of those who were deemed too healthy to be treated so I dealt with Gilead on my own and self paid. The problem is that I exhausted all of my credit on paying for 8 weeks Harvoni and can only hope that should I relapse, that I will be so lucky as to fit into a clinical study. I am not sure how many Canadians are part of clinical studies these days.....
I have noted that men relapse more than women in the studies I have been devouring but I am also a woman who was treated just after menopause as opposed to before it.
I will post my results as soon I receive them.
Oh and I hope my writing is satisfactory. Ha ha. ;D If not, chalk it up to autocorrect.
Kim in the Boreal
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Hey Kim...Good luck on your tests, and remember those sharp pains could be coming from your gallbladder as well. I have some tiny stones and every once in awhile they remind me of that. Keep the faith, girlfriend. I am here for you!
Katie
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Hi Katie,
So I got my 4.5 week viral load done and it came back undetected! Specifically, target not detected! I am feeling relieved to say the least. Now, while I await the 12 week test, I feel more optimistic.
You and Lynn were clearly right. 8)
So how are feeling now Katie? Have things returned to normal or somewhat for you?
Kim
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Hi Kim! Great news! Way to GO! You are on your way. I never had an undetected until round 7 weeks post treatment so I am confident you have won the battle. My response was strong with a drastic drop in the VL right away but then it just stayed at <15 and still detected. I know there have been some relapses but very few.
I am doing better each day, and of course spring helps. I have been working in the gardens, which always rejuvenates me. I must admit, I had to force myself to start but now look forward to it. Firm believer in the more you do, "the more you are able to do".
I got my 12 month post treatment VL check along with an extensive battery of tests and my blood work came back Absolutely Perfect for every single thing. It has never been better and so that really told me how much better I am really doing....and I am on no medication. The doctors are always amazed as I will be turning 70 this year. Have no idea how that happened! HA! Time flies, huih?
Continue to take good care of yourself, and if that pain continues you might ask about having an abdominal ultra sound.
Take care girl friend!
Katie
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Hi Katie,
I am glad to hear that you are doing well. Spring has a way of renewing one's spirits.
I should mention that I don't have sharp pains but rather, a dull twinge every now and again. I am not really sure it even counts as pain as it is quite mild. Having said that, it was one more thing to add to the waiting paranoia.
Congrats on being 69 young, cured and with a clean bill of health.