TOPIC:

Hi.

I wonder if anyone can give me an answer. On tx we all reach UND, which is the virus not detected, but how can some people relapse.

Where is the virus coming from?

Being UND doesn't mean that every virus is killed. some viruses reside deep in the body. Some viruses may hide. But this is not the case with the new treatment where many have been detected at EOT and still cured.

Well, like I said in the previous thread, best I can see the majority who fail don't reach UD during
the 12 weeks they are usually 12 throughout then post treatment the virus is no longer being
suppressed via medications therefore it comes back.

There is a small percentage, I mean tiny who are UD during the 12 weeks and the virus also
comes back they don't know why, these treatments are new its gonna take some time to figure out
why some maybe resistant to treatment.

Lastly, they have being retreating those who fail with success it seems these people react better
to extra DAA.

best I can see the majority who fail don't reach UD during
the 12 weeks they are usually 12 throughout

I don't agree Sir. People do routinely reach UND without all the virus being gone. The PCR test just isn't sensitive enough to detect what's left. If we had a test that really could detect every virus then it would be much simpler. We'd know when we got the UND result that we could stop tx.

dt

Agree dt,

UND doesn't mean 'None there!', rather it is 'I can't see any?'.
and the test can't determine whether the RNA it can see is viable or not which is why some who are still detected at EOT go on to a SVR.
Then there is the question of whether some who 'relapsed' may have actually been reinfected post treatment?

Viral load tests are imperfect.

There is very little viral RNA to to count it we use something called Polymerase Chain Reaction - this amplifies the quantity to something we can count.

The Lower Limit of Quantification (LLOQ) may be 30, 25, 15, 12 or 10 and virus that can be detected, but is at a lower level than this results in a <30 detected, <25 detected, ... <10 detected.

The Lower Limit of Detection (LLOD) is the smallest quantity that can be seen. A test with LLOQ <15 will have an LLOD of around <6 so RNA in the range 0-5 will come back as undetected.

When we see the rapid drop in HCV RNA this is all the easy stuff being killed. The problem is the mutants which are present in low levels. They are present in low levels because they don't grow as fast, but kill off all the faster growing stuff and you are left with the mutants.

Think of it like pulling all the plants out of a garden to leave raw earth. Pretty soon weeds take over the empty space.

So recurrence comes from hard to kill mutants that were present below the LLOD at the end of treatment. In other words the undetected was really "can't detect with the sensitivity required". For this reason we over treat everyone. 8 weeks Havoni for GT1 naive with low fibrosis gets at 121/123 SVR if the viral load is < 6 million to start with.

A high viral load is a negative predictor because it says 1) your body is not doing a good job killing it and 2) there are more virions, so more mutants.

Thanks Dr. James for your explanations!
Some mutants are hard to kill
Hope to kill them all!

This has always been my instinct Dr F - and now you have given those little hardcore cells a name, 'The Mutants'

Wanting those mutants gone. I currently have flu, hope it doesn't make it harder to kill those evil mutants off.

Thanks Dr James
The test performed on me at Day 25 says measured in the assay range 30-100000000 and I came back as <30 but the doctor yesterday at the liver clinic called it "still detected" not UND yet?

I'm at week 5 now and have 7 to go with no liver damage and this first blood result is therefore good.

So my next path sheet handed to me is for the same clinic and the same requests
Does this mean it's always going to just come back <30 I am confused?

Or does this test somehow show up UND?
I'm attaching a screenshot of yesterday's result.
Thankyou James for this awesome medicine and your assistance with understanding this report
Ariel

We discussed this privately but <30 mean old machine!

There is not an undetected or detected notation on this (which there is on most of the results)

Use a lab that does <15

The lower limit of detection is about <6 so anything in the range 0-5 will be undetected.

You need a real zero to clear but we can't measure that low, so we over treat by a working safe margin.

With GT1 for example SVR is typically 97% at 12 weeks (depends on your profile) but 99% at 24 weeks. To a government/insurance payer the extra 2% of not worth the extra 100% cost. If we just treated the 3% failures with 2 x the treatment length the cost only goes up 6% so it's a pretty logical decision to do 12 weeks and retreat failures for 106% when you weigh it up against spending 200% in the first instance to get there.

If you are privately paying you might reasonably decide that you would prefer 100:1 odds rather than 33:1 and opt for 24 weeks, but it is overkill for 97% and the last 12 weeks will be going into a body with no HCV.

Not an easy choice but you have to draw the line on treatment duration somewhere.