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If you are UND at 4 weeks what are the DAAs doing afterwards? 6 years 4 months ago #15521

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Hi all,
Hope this is not a silly question.
As I understand it the new DAAS go to work on the virus that is present in the liver.
Say you are UND at week 4 or at some other time prior to week 12, what do the DAAs do?
I get that there will be some stragglers coming into the liver via the bloodstream from other parts of the body where they have been doing their evil work but at some stage there will be none left.
Just wondering :unsure:
Genotype 1a
Diagnosed in 2004, had HCV for all my adult life. Until 2016!!!!
Harvoni treatment, started 19 March 2016
4 week results Bilirubin 12 down from 14 pre treatment,
Gamma 25 down from 52, ALT 19 down from 63, AST 19 down from 47,
VL <15 down from a lazy 6 million or so

EOT Results
Bilirubin 10, GGT 18, ALT 19, AST 21, VL UND

12 Weeks post EOT
Bilirubin 11, GGT 16, ALT 22, AST 20, VL UND
Cured baby
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If you are UND at 4 weeks what are the DAAs doing afterwards? 6 years 4 months ago #15522

  • sonix
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You answered your own question. Yes the DAAs will be mopping up stragglers that are hiding, but as they are not in the bloodstream they can't be detected by a blood test. It's been mentioned that it's better to continue treatment after UND for a while to make sure those hiding viruses have a better chance of being killed.
M 61yo HCV+ ~ 30 yrs Gt1a F2 VL 223,000 ALT 54 AST 42 Tx start Sof/Dac 17Dec15.
SVR4 at 7Apr16 ALT 22 AST 22
SVR12 at 9Jun16 ALT 23 AST 25
Melbourne, Australia
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If you are UND at 4 weeks what are the DAAs doing afterwards? 6 years 4 months ago #15523

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As sonix says. The virus that are in your liver and other parts of your body are a bit harder to get the medications to. This is more so with fibrosis or cirrhosis. Think of the scars of cirrhosis as little walled off forts that the virus can hide in, it takes longer to get the medication past those barricades. As we don't know exactly when this happens we rely on the original trials that told us that we needed to treat for x number of weeks in different situations to be reasonably sure of getting all the virus.
G3a since '78 - Dx '12 - F4 (2xHCC)
24wk Tx - PEG/Riba/Dac 2013 relapsed
24wk Tx - Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx - 12/01/17 -> 03/05/17 NS3/NS5a + Generic Sof
SVR7 - 22/06/17 UND
SRV12 - 27/07/17 UND
SVR24 - 26/10/17 UND
:cheer: :cheer: :cheer:
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If you are UND at 4 weeks what are the DAAs doing afterwards? 6 years 4 months ago #15528

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But when there is nothing for them to work on, what do they do?
I think I must have let too much sea water into my brain this morning.
Genotype 1a
Diagnosed in 2004, had HCV for all my adult life. Until 2016!!!!
Harvoni treatment, started 19 March 2016
4 week results Bilirubin 12 down from 14 pre treatment,
Gamma 25 down from 52, ALT 19 down from 63, AST 19 down from 47,
VL <15 down from a lazy 6 million or so

EOT Results
Bilirubin 10, GGT 18, ALT 19, AST 21, VL UND

12 Weeks post EOT
Bilirubin 11, GGT 16, ALT 22, AST 20, VL UND
Cured baby

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If you are UND at 4 weeks what are the DAAs doing afterwards? 6 years 4 months ago #15532

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Hi beaches,

We can only measure the ones in our blood, we can't directly measure the ones in the liver which take longer for the medications to reach and kill. So we kill the ones in the blood that we can measure and then keep going for long enough to make sure all the others are killed too.
G3a since '78 - Dx '12 - F4 (2xHCC)
24wk Tx - PEG/Riba/Dac 2013 relapsed
24wk Tx - Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx - 12/01/17 -> 03/05/17 NS3/NS5a + Generic Sof
SVR7 - 22/06/17 UND
SRV12 - 27/07/17 UND
SVR24 - 26/10/17 UND
:cheer: :cheer: :cheer:
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If you are UND at 4 weeks what are the DAAs doing afterwards? 6 years 4 months ago #15541

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Beaches, you may not have seen this
Vororo put this up 13 weeks ago in Media & News :+1:
it may help with understanding some of the complexities
gt 1a VL 6m
F2/3 FibroScan - 9KPa in 2011 and 7KPa in 2015
sof/dac 10 December for 12 weeks
pre tx alt 85 ast 51
4 wk alt 34 ast 31 UND <35
8 wk alt 29 ast 32 UND <15
12wk alt 25 ast 25 EOT 3.3.16
SVR24 UND KPa5.3 F0 in normal range
I am well
.forever grateful to fixhepc
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Last edit: by pat1.

If you are UND at 4 weeks what are the DAAs doing afterwards? 6 years 4 months ago #15546

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Thanks for reposting this Pat1 it is an excellent video that is also good to help people who have not ever had the virus to understand the seriousness of a diagnosis. I have seen it before too and think it's an excellent tool for educational communications. For those of us who have told family or a few friends these types of videos help them.

High drama and scary things are all over YouTube even herbal retreat things which apparently will cure the universe, you name it it's there! (Back in peginf days I watched many YouTube offerings nothing offensive fortunately but certainly not proper information)
Those types of videos only serve to water down the serious nature of HCV I believe.

This is an excellent vid. Thanks again
Ariel :+1:
Gen 1a
Peg/inf/riba 2012(!) stop @ Wk 43 potassium low +issues (rlps week 4 post tx, VL120,000) scnds eg. adenomas.
pre sof/led VL 240,000 Fibsc F0
Day 25 <30
Day 32 UND
Week 10 UND
EOT UND ALT11AST17GGT19
SVR4 UND ALT10 AST16 GGT13
SVR8 UND ALT <9 AST16 GGT15
SVR12 UND ALT14 AST19 GGT12 Bili 5
EOT +18 ALT13 AST20 GGT9 Bili 5
EOT +21 ALT11AST15
Cured SVR12
Dysplasia Adenomas RemvdAug '16
SVR24 UND ALT11AST16
ColonoscopyClear Nov17
LumpectomyClear ‘18
LithotripsyCytoscopyBiopsy 4/18
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If you are UND at 4 weeks what are the DAAs doing afterwards? 6 years 4 months ago #15550

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Thank You Pat1, that is very very informative. :+1: #love
Being a bear of little brain I can't say I understand all of it but I have a better picture for sure.
It seems I was misinformed about how the HCV DAAs work too. I thought they acted on the cells in the liver, but it seems they work their magic in the blood stream.
My 8 week bloods are due at the end of next week (where did that time go?) so hopefully the only way is up, baby
Genotype 1a
Diagnosed in 2004, had HCV for all my adult life. Until 2016!!!!
Harvoni treatment, started 19 March 2016
4 week results Bilirubin 12 down from 14 pre treatment,
Gamma 25 down from 52, ALT 19 down from 63, AST 19 down from 47,
VL <15 down from a lazy 6 million or so

EOT Results
Bilirubin 10, GGT 18, ALT 19, AST 21, VL UND

12 Weeks post EOT
Bilirubin 11, GGT 16, ALT 22, AST 20, VL UND
Cured baby
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If you are UND at 4 weeks what are the DAAs doing afterwards? 6 years 4 months ago #15554

At some point along the road to cure we are giving the medication, but there is no virus.

This medication simply hangs around in the tissues and is excreted out of your body every minute of every day. After about 5 days on treatment your body is excreting almost exactly a full dose of medication each day. You are taking more medication to top up this loss, but the level remains relatively constant (it actually looks like a saw tooth pattern with the highest level about 1-2 hours post taking your dose, and the lowest just before you take a new dose.

The reason that we need a period of over treatment is that UND does not mean "there is no virus". It means there is not enough virus to see and this could represent 0 (as in cured) or something in the range 0.1 - 10 depending on the sensitivity of the test.

During the post treatment period if there is remaining virus the drugs wash out of your body, and the virus regrows. If there is no virus left (ie truly undetected because it is not there) you have SVR.
YMMV
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If you are UND at 4 weeks what are the DAAs doing afterwards? 6 years 4 months ago #15559

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Thanks so much for your responses and time, Doctor James aka legend and everyone else #flower
Genotype 1a
Diagnosed in 2004, had HCV for all my adult life. Until 2016!!!!
Harvoni treatment, started 19 March 2016
4 week results Bilirubin 12 down from 14 pre treatment,
Gamma 25 down from 52, ALT 19 down from 63, AST 19 down from 47,
VL <15 down from a lazy 6 million or so

EOT Results
Bilirubin 10, GGT 18, ALT 19, AST 21, VL UND

12 Weeks post EOT
Bilirubin 11, GGT 16, ALT 22, AST 20, VL UND
Cured baby
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If you are UND at 4 weeks what are the DAAs doing afterwards? 6 years 4 months ago #15575

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James-Freeman-facebook wrote: This medication simply hangs around in the tissues and is excreted out of your body every minute of every day. After about 5 days on treatment your body is excreting almost exactly a full dose of medication each day. You are taking more medication to top up this loss, but the level remains relatively constant (it actually looks like a saw tooth pattern with the highest level about 1-2 hours post taking your dose, and the lowest just before you take a new dose.
.


Sorry, but this has just prompted another question in my mind.
I'm sure I read a thread about Harvoni fatigue, but looking at Dr James' comment, it seems that no matter how long you take it, after the initial 5 days the dosage in your body remains the same (apart from the daily fluctuations).
Does that mean that after those first 5 days you should feel pretty much the same apart from feeling better as the virus disappears and apart from any incidental things that might happen such as colds etc?
Genotype 1a
Diagnosed in 2004, had HCV for all my adult life. Until 2016!!!!
Harvoni treatment, started 19 March 2016
4 week results Bilirubin 12 down from 14 pre treatment,
Gamma 25 down from 52, ALT 19 down from 63, AST 19 down from 47,
VL <15 down from a lazy 6 million or so

EOT Results
Bilirubin 10, GGT 18, ALT 19, AST 21, VL UND

12 Weeks post EOT
Bilirubin 11, GGT 16, ALT 22, AST 20, VL UND
Cured baby
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If you are UND at 4 weeks what are the DAAs doing afterwards? 6 years 4 months ago #15595

Thanks for posing these questions beaches, knowledge will set us free!! :idea: :+1:
GT1a; Got it some time in the 70's; Diagnosed @1976
Tx naive
METAVIR: A2-F2
SOT May 18, 2016: CMP: AST 162 ALT 241 VL 13000000
3 weeks after SOT: AST 27 ALT 31 VL 138
Reached EOT Aug. 10, 2016 / Received svr4 results Sept. 20, 2016: AST 22 ALT 24
Hep C RNA "NOT DETECTED"
AS OF 3/20/2017 ,Hep C RNA PCR "NOT DETECTED" THAT'S SVR24!

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If you are UND at 4 weeks what are the DAAs doing afterwards? 6 years 4 months ago #15645

I am more concerned about what happens to all the remotes.....

When you pick up the remote controller it sprays out remotes, but it only takes 1 remote to turn on the A/C or the TV, so what happens to all the rest?

What if they were just hanging around, plotting?

Sometimes I wake up in a sweat worrying that all these lost remotes will develop a collective consciousness and take over the world, after all, they already know how to control almost everything!

But more seriously if you look at the blood levels as you start taking medication it looks like this:




So the levels increase rapidly to start with then reach a steady state where each day almost all you take in is excreted.

The almost is because you never quite reach steady state but it goes up like 1/2, then and extra 1/4, then an extra 1/8, 1/16, 1/32 and if you add all those up you never ever quite get to 1.
YMMV
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