TOPIC:

Yes Cruzan,
You are GOOD!
Responding to treatment great!
on your way to UNDETECTED!!!
Mike

Hi GAJ,

These labs or collection centres get these tests wrong, as at first glance, the names can be misleading, (Quantitative or Qualitative ) BUT the poor patient who is waiting on the edge of their seat for anything up to 2 weeks, then to get the wrong test result is not good to say the least .

Hi DT,

Thanks for the great explanation about the genetic markers. I am IL28B CT and I hadn't fully realised the impact that these two little letters could potentially have on the outcome of interferon based treatment. Mid last year the Dr at the liver clinic was still recommending interferon with very little discussion about success rates and certainly nothing about the genetic marker which I just happened to see in a blood result.

It really is so important to keep yourself informed which is why this site and all involved in this adventure are so fantastic.

Cheers
Coral

Hi Coral,

Yes, I am appalled that ifn-based tx is still being handed out without the IL28B test being done. NHS UK is still not doing this test as far as I know. It is not the only predictor of SVR but it does have bearing on the outcome. So people with an urgent need to treat will probably still do so regardless, but people who could wait might be advised to wait if ifn is their only option.

For people like me who have had a viral breakthrough, I nearly hit the roof when it was suggested that I had been non-compliant with the tx. To be fair, the nursing staff have to ask that question. But they shouldn't blame the patient for non-compliance when their genetic marker already indicates a poor outcome. That is unjust and adds insult to injury.

For people who do get the IL28B test and are not a CC, I think that they are entitled to argue against an ifn-based tx being appropriate for them. If the medical provider COULD recommend a DAA tx but is choosing instead to offer an ifn-based tx then you have an argument for getting the DAAs. A lot of money is being spent on ifn-based tx for CT and TT people for whom a poor outcome could be expected. This does not make any financial sense for the provider and could save a lot of heartache and suffering for the patient. I have to wonder if the IL28B test is deliberately not being done by some medical providers precisely because they do not want their patients to come up with this argument and make them pay for the DAAs.

dt

Anyone giving someone interferon at this time shoud have to take it as well.
In jail.
M

Investigating many patients cured at others forums, being UND or < LLOQ (<15) is insignificant. Even patients that have been detected at EOT but < LLOQ have been cured. At the time of trials with Harvoni the LLOQ have been 25 IU/ml, now they have updated to 25 and 15.
Other patients on Harvoni have been UND at 4 weeks and then detected at 6 weeks followed with UND at 8 weeks and still cured with three months treatment.

From Gilead Page:
HARVONI was administered once daily by mouth in these trials. For subjects who received ribavirin (RBV), the RBV dosage was 1000 mg per day for subjects weighing less than 75 kg or 1200 mg per day for subjects weighing at least 75 kg. RBV dose adjustments were performed according to the RBV labeling. Serum HCV RNA values were measured during the clinical trials using the COBAS TaqMan HCV test (version 2.0), for use with the High Pure System in ION-3, ION-1, ION-2, SIRIUS and ION-4 studies or the COBAS AmpliPrep/COBAS Taqman HCV test (version 2.0) in ELECTRON-2, and 1119. The COBAS TaqMan HCV test (version 2.0) for use with the High Pure System has a lower limit of quantification (LLOQ) of 25 IU per mL and the COBAS AmpliPrep/COBAS Taqman HCV test (version 2.0) has a LLOQ of 15 IU per mL. Sustained virologic response (SVR12) was the primary endpoint and was defined as HCV RNA less than LLOQ at 12 weeks after the cessation of treatment. Relapse was a secondary endpoint, which was defined as HCV RNA greater than or equal to LLOQ with 2 consecutive values or last available post-treatment measurement during the post-treatment period after achieving HCV RNA less than LLOQ at end of treatment.

From Gilead Page:
HARVONI was administered once daily by mouth in these trials. Sustained virologic response (SVR12) was the primary endpoint and was defined as HCV RNA less than LLOQ at 12 weeks after the cessation of treatment.


Thank you, Enkel, for pointing out (post#7415 on this thread and some other posts on other threads) that SVR12 is, apparently, not limited, as I had previously thought, to being HCV RNA undetected at 12 weeks after the last dose of treatment. Thanks also for backing this up with the quote above from a Gilead document which states that the definition of SVR12 used for the ION clinical trials into Harvoni (sof/led) was being below the LLOQ (Lowest Limit of Quantification) at 12 weeks post EOT (end of treatment). I assume that if this is the meaning of SVR12 used by Gilead in the ION trials it must be a meaning which is accepted not just by Gilead but also by the wider medical and scientific community.

It seems to me, if my understanding is correct, that, potentially at least, being below the LLOQ is not quite the same thing as being undetected at 12 weeks post-EOT (although clearly it includes being undetected at 12 weeks post-EOT). Is this correct? For example, does being below LLOQ for this purpose include being <LLOQ DETECTED as well as being <LLOQ UND at 12 weeks post-EOT?

This question isn't answered by the quote (above) Enkel provides from the Gilead document.

So, is the upshot of this that while the meaning of SVR12 includes being undetected at 12/52 (i.e. 12 weeks) post-EOT it is not limited to it? The meaning of SVR12 used by Gilead (above) seems to be a little more forgiving than this. It also includes having HCV RNA below the LLOQ (Lowest Limit of Quantification) at 12/52 post-EOT, which may also include, although I am not sure about this and I stand to be subsequently corrected here, being below LLOQ DETECTED.

This question may have practical implications. For example, does it mean that the best VL test to do at 12/52 post-EOT may be quantitative and not qualitative? The qualitative test is more precise at very low levels of HCV RNA but might it not also be too strict for the purpose of establishing the broader, more lenient definition of SVR12 given in the quote above? My understanding is that the qualitative test is reported simply as either detected or undetected. If this is so, then although the qualitative VL test is best for determining the more strict definition of SVR12 it would fail to identify the lenient definition of SVR12 because it cannot distinguish the result <LLOQ DETECTED, and hence potentially at least (depending on the answer to my question above) still within SVR12, from any result equal to or >LLOQ, which would constitute relapse and failure to attain SVR12.

Another thing that puzzles me about this more lenient definition of SVR12 is that if someone achieves UND at EOT but then their VL test comes back <LLOQ DETECTED at 12/52 post-EOT does this still amount to SVR12? They are below LLOQ at 12/52 but the direction of change in their VL load seems to be going the wrong way – it's getting worse, not better.

If < LLOQ still there is chance of cure. With Vikiera Pak the LLOD (Lowest Limit of Detection) is the measure of SVR but with Harvoni LLOQ is the measure.

"Relapse was a secondary endpoint, which was defined as HCV RNA greater than or equal to LLOQ with 2 consecutive values or last available post-treatment measurement during the posttreatment period after achieving HCV RNA less than LLOQ at end of treatment."

It is intersting that with the regiment including sofosbuvir, detected at EOT and even later still have higher cure rate. But of course the longer the treatment the better because the more defective replication complex is induced

"There must be other reasons to explain the high SVR," Guedj said. "We think most of the [newly produced] virus may be uninfectious...treatment may have the effect of replacing a working replication complex with a defective replication complex, which explains how most patients could clear the virus in 6 weeks."

"Low negative predictive values of HCV RNA at week 4 underscore the importance of continued therapy for patients who fail to achieve undetectable levels of HCV RNA early on during treatment because the likelihood of achieving SVR12 is still high," the researchers concluded. "Contrary to past experience with interferon-containing treatments, the presence of detectable HCV RNA at EOT [end of treatment] is not predictive of relapse in these studies."

www.aidsmap.com/HCV-viral-load-levels-du...herapy/page/2962856/
An uninfectious virus may only explain these data of this person:
Started Harvoni 11/26/14 for 8 wks
Completed 8 wks Harvoni 01/20/15
EOT RNA Quant result: Detected 29
7.5 wk post tx: Detected < LLOQ(12)
11 wk post tx: UNDETECTED SVR12
24 wk post tx: UNDETECTED SVR24; AST 26; ALT 22
48 wk post tx: UNDETECTED SVR48

Hi,

maybe a 'bit off topic' but what about the possible outcome of never achieving a SVR?

From what I have read, it appears that HCV's symptoms, and I hope damage, is limited during treatment. For me I need 24 weeks and finish the first 12 weeks on my birthday! Feel better on DAA's then before when not on them, but there is the chance of still no SVR.

Being the product of warehousing due to Interferon not working previously I have had to watch my liver being bounced around, a dismal pastime not enjoyed by myself or the medics that have helped me for that matter, over many years. The liver is now scarred and sported a 4.9cm tumour for a while as well.

If no SVR, my questions are:

1. say another tumour decides to keep company with my liver, is staying on DAA's likely to be some part of palliative treatment?

2. if the liver stays okay but the bug is not eradicated fully with the likelihood of coming back in the millions post treatment, is staying on DAAs something that medically could be indicated? Maybe delay another HCC if one is on the cards?

3. if the DAA's cannot always get into the upper reaches of my liver's scar tissue and there then is a reliance on my immune system finishing of what's left, does this put Interferon (just before and a bit after EOT) back on the table?


Yours


J.


P.S. didn't mention the costs, but think of the windfall Gilead could make if people such as I were on DAA's indefinitely; they would need to lower the cost though, but I don't think their bean counters have enough sense to think that way and I think they would put gouging before profits just to be sociopaths.

If SVR isn't achieved then they can test and find out why not Sabrecat. Plenty of cirhotics have cleared the virus with stuffed livers J.

The way I see it is most of us here are motivated and really want this to work therefore we stick to the treatment regime which puts us in the > 95% category.

cheers

From Dr James

Yes to B12 and D

No to retinol, C, E, K and selenium

fixhepc.com/forum/experts-corner/566-sup...-hcv-viral-load.html

Sabrecat,

I can't directly answer your questions but here's what I know.

Q2
In the days of interferon it was also thought of that people who did not reach SVR might be put on a 'maintenance dose' indefinitely to protect their livers until a cure came along. It was tried but without much success. I don't see why it couldn't be tried with the DAAs too.

Q3
Again in the days of interferon, it was thought that there might be a reliance on the immune system to finish the job and get to SVR. For a while it was theorized that svr would not be possible without interferon, for this reason. So when the first svrs were achieved without interferon it really revolutionized that thinking. It was then theorized that if a person became resistant to all DAAs then interferon would once again become their only option. I don't know how it goes from here. We've had an 'arms race' with bacteria and antibiotics which the bacteria are on the verge of winning. We are just starting an 'arms race' with viruses.

There was a guy on medhelp who had HCC. He got a liver transplant and he got to SVR with the DAAs. The most important thing about his story was that he had a fantastic medical team at the transplant liver centre who got him through all kinds of complications. Hopefully it will not come to that for you, but that's what you need if you don't get to SVR.

dt

Hiya
Hoping someone can help me out - Ive just this moment got my 4 week VL back and wondering if the following values mean that the virus is no longer detectable.....

HCV RNA IU/mL <12

HCV RNA log log IU/mL <1.08

Thanks in advance to whoever can confirm this for me

P.S hope this is the appropriate thread for my question.

Hi Sabrecat,

Being in a similar health and treatment situation to you can I just say that I have every confidence that we will both achieve SVR and remain so.

Particularly given our incentives, both cash and health wise, to be dosage compliant throughout our treatment. As my specialist said ".....at this point I usually give patients a lecture about taking the meds as directed but in your case I guess we can skip that!"
I have also stocked up on vitamins B12 & D and made an appointment this week with my GP for tests just to see if I need an initial shot to get me back up to optimum levels.

Any further tumours need to be found and treated as soon as possible for the best prognosis so make sure you are getting checked as regularly as possible. While your occurrence was at least 3 years ago, if it was me I would be talking with my specialist about three monthly scans while on treatment and a period after even if I needed to pay for some myself.

For others who may fail to achieve SVR, while not an expert, my thoughts are that staying on treatment with DDAs is not likely to be optimum. As Paul said, they would need to determine why they failed via testing and then look for alternative treatments such as Velpatasvir instead of Daclatasvir or possibly a three way treatment using Simeprevir (speculating with these suggestions)
There is also discussion that for some Gt3 patients, Interferon plus a couple of DAAs throughout treatment may work well but I know in my case Interferon has basically been ruled out for retreatment due to my IL28B status.

Same as my 4 week treatment. Yes it means positive - detected. But below 12.
I've just had my 12 week PCR RNA Viral Load back today & it was negitive - Undectected.

Thanks Hamilton

So not yet but SOON - I can live with that

I'm looking forward to when I can unleash the UNDECTED montage in the party room.

Congrats to your result, especially after failed previous Tx, onwards to SVR for you!