12 week PCR and Genotype 1A

[pixie]

Hi  everyone I can`t tell you how guilty I feel not dropping by so much....Not sure where the rtime goes...one week today and the Heppers start arriving on the farm for our Wedding on Monday 19th May WHAD....

I thought you might be interested in seeing this tho.....

 Rossweiler on Fri May 09, 2008 11:21 am
Ribavirin exposure after the first dose is predictive of sustained virological response in chronic hepatitis C.


Loustaud-Ratti V, Alain S, Rousseau A, Hubert IF, Sauvage FL, Marquet P, Denis F, Lunel F, Calès P, Lefebvre A, Fauchais AL, Liozon E, Vidal E.

Centre Hospitalier Universitaire (CHU) Limoges, Internal Medicine Department, Limoges, France. veronique.loustaud-ratti@unilim.fr

The impact of ribavirin exposure on sustained virological response (SVR) in patients with chronic hepatitis C is unknown. Preliminary studies showed marked inter-individual variability of ribavirin concentrations despite dose adjustment for body weight (BW) and suggested there was a correlation between single time point concentrations and SVR. None of them evaluated the global exposure to ribavirin. This study was conducted to determine whether early ribavirin global exposure is related with SVR. An exploratory pharmacokinetic-pharmacodynamic (PK-PD) study was conducted in genotype 1 hepatitis C patients treated with peginterferon alfa-2a and ribavirin (dose-adjusted for BW) for 12 weeks, to which amantadine was added for the following 36 weeks. Full and abbreviated ribavirin area under the concentration time curves (AUC(0-12h), AUC(0-4h)) were derived from plasma concentration profiles at day 0 (D0), week 12 (W12), W12 + 1 day, and W24. Virological follow-up was performed at D0 (0, 12, and 24 hours), W2, W4, W6, and monthly until W72 (TaqMan polymerase chain reaction, cut-off 15 international units/mL). Twenty-eight patients were enrolled in the study and 24 completed it. Patients with a SVR had a significantly higher D0 AUC(0-12h) (3695 [1571-6916] versus 2937 [1266-4913] microg/hour/L, P = 0.03) and D0 AUC(0-4h) (2010 [615-3175] versus 1340 [622-2246] microg/hour/L, P = 0.03). Patients with D0 AUCs above the cut-off values defined by receiver operating characteristic curves (3014 microg/hour/L and 1755 microg/hour/L for AUC(0-12h) and AUC(0-4h), respectively) had a significantly better chance of achieving an SVR than patients with AUCs under the thresholds (odds ratio = 16.0, 95% confidence interval 1.54-166.6, P = 0.02 and odds ratio = 8.9, 95% confidence interval, 1.4-56.6; P = 0.02). CONCLUSION: Ribavirin exposure at D0 is significantly related to SVR. To our knowledge, this is the first study to give an early pharmacokinetic predictor of SVR. We propose a minimum AUC(0-4h) threshold of 1755 microg/hour/L at D0 as a target for ribavirin dose adjustment.

PMID: 18435468 [PubMed - in process]

Related Articles

* Clinical trial: exposure to ribavirin predicts EVR and SVR in patients with HCV genotype 1 infection treated with peginterferon alfa-2a plus ribavirin. [Aliment Pharmacol Ther. 2008]
* Virological response in patients with hepatitis C virus genotype 1b and a high viral load: impact of peginterferon-alpha-2a plus ribavirin dose reductions and host-related factors. [Clin Drug Investig. 2008]
* Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus


Just to give you some info on Ross and this is his way of doing tx and is always worth a debate, he calls it Flying by the seat of his pants tx....

Ross was a relapser and has decided to modify his own tx this time round, he built up on riba`s ..This is his tx



12 days of Ribavirin build-up prior to the first shot at Mega-Dose (3000-4000mg per day) , my normal weight dose is 1200mg per day.

2 x weekly shots of 150mcg Interferon Alpha 2b (PegIntron) 3.5 days apart (if I was taking Interferon Alpha 2a I would take the shots at the same time)
Most weeks have been 1 x 150mcg shot and 2 x 80mgc shots, so even here I have dosed at least 10mcg over double dose.

Daily Ribavirin dosage has stayed at around 2400mg per day

This regime has been followed until Yesterday (6.5 weeks) , at this point I have stopped the double Interferon shots and reduced my Ribavirin to around 2000mg per day.

This is my 2nd round of treatment Vega, my first round was (or seemed at the time) going swimmingly). My dosage then was 1200mg of Ribavirin daily and a 180mcg shot of Interferon Alpha 2a per week . My baseline vl was 24+million and my first PCR was at 12 weeks and was undetectable. I was undetectable at 12,24 and 36 weeks , but the virus was back at 11 weeks post Meds.

This round of treatment is very much my own design and called the Flying by the seat of your pants Trial.

Its based on only a couple of knowns:

Hit the virus the hardest you can from day 1, as the faster you get to undetectable the better the eventual prognosis (cure ?).

HCV needs Red Blood Cells to replicate fast, remove enough of them (high Ribavirin dose and build-up) and things start getting really difficult for the virus, with 2 shots of Interferon per week.

My Consultant has a slight inkling (I'm sure) what I've been up to, but would probably be horrified if she knew how I achieved RVR in 4 weeks with a vl of 16+ million. She will know of course , because I must be honest about this with her, but I cannot afford to jepordis my ongoing Med supply, so for now she must remain in the dark.

I have had weekly Bloods done , all of which results, I get within the same day as the sample given and adjust the Ribavirin accordingly.

The secret is healthy Platelets to start with (275+), then the journey is much smoother , as blood cell production (replenishment) seems to be intrinsically linked to a high Platelet count

What I have done was calculated, all of the extra Meds needed were donated by Forum members across the globe, without these many supportive friends, what I have done would not have been possible, so thank you with all my heart.


Ross xxxxxxxxxxxxxxxx




He got RVR in 4 weeks this time round and his bloods are still ok..heres some results check the dates.

y Rossweiler on Thu Mar 13, 2008 6:29 pm
Hi CS

Well today is Bloods day and I thought I'd better post my results, as you worry worse than my mother.

11.1 Hb

2.3 Wbc

0.8 Neuts

234 Platelets

18 ALT

16 Bilirubin

My Ribavirin daily dose is at present 1600mg (from this last Monday), but will be increasing from this coming Monday to 2000mg per day.

Ross xxx


Hi

It appears that even when my Hb is 11.1, 2 weeks of 3000mg Ribavirin per day, does not knock it toward the magic 10, but it goes up to 11.6. I'm going to give this one last try (to get it down to 10) and next week I'll poke it up another 1000 per day.

My body also appears to be laughing in the face of Interferon Alpha 2b, 2 weeks ago my Neutrophils were 0.7 and after 2 weeks of double dosing , they have gone back-up to 1.5 .


Bloods from 25/04/2008

Hb 11.6

Wbc. 2.5

Neutrophils 1.5 (makes me think that the 0.7 last time was a false reading)

Platelets 254

ALT 25

Bilirubin 17



Bloods from 11/04.2008

Hb 11.1

Wbc. 2.2

Neutrophils 0.7

Platelets 267

ALT 23

Bilirubin 17


Ross xxxx

PS

He's a Scientific Miracle !

His Sides from this...


n a singular type word buggered !

Sides

Chronic Fatigue 24/7.

No appetite.

No will to do anything at all.

Headaches ..... always wake with one.

Skin falling off (especially in ears)

Sore ears.

Totally dry and horrible inside of nose

Hair all gone (razored it all off..... as it wasn't mine anymore)

Blistering , pustuling scalp

Scabby Scalp/Itchy Scalp

Nausea/Vomiting (not too much)

Aching body after each shot (Sunday Pm & Thursday am )

Fever, Sweats

Dry skin all over my body

Short term memory (whats that?)

Concentration (whats that ?)

I can't think of any others, as my head hurts !



So , my 2nd round of treatment is a little harder than round 1, but most of it is probably because of the excessive doses that got me RVR at 4 weeks, so I cannot really complain !

R xxxx



I will say do not try this at home.. ...But it is worth debating whether this way should be for relapsers, jb will also be going down this road perhaps not as extreme as Ross ....But certainly trying to get his Hb low as he can.....

Will check back soon luv ya all..................PXXXX

[negative1]

Wow Pix,

First of all, it was great to see you pop back in!

Secondly, what an interesting bit of info here.

I was a 1, stage/ grade 2/ 2-3 and did 48 weeks and at the time, they did not do a 4 week test but rather the 12 week to see if I was responding. I did show undi at week 12.
What I find interesting here is the massive riba dose.
The normal dose that I have seen everyone get for riba is 1200. Now my doc started me at 1400. I have not known anyone to get that dose. My reds dropped fairly fast and got down to 8. I do not really know when that happened though, since I was good about my blood work for the first couple months going in every 2 weeks...but then, I really don't know if I was just hating it, forgetting it or just not wanting to get stuck by another needle, but I stopped going in for blood work. I did not go in for about 6 weeks or so....hey what will be will be. When I did go in, they found that my reds were at this low level and started me on Procrit. In fact, I do not remember if I even did my pcr at 12 weeks exactly or just * around* that time.

Maybe my success, in regards to this info, was due in part to taking the bigger dose of riba AND having my low reds count.
I could be totally wrong here, but it does give one a reason to consider this.

Thanks!

Earl

[Lee]

Earl,

I am on week 14.  They tested at 6 weeks and I was undetectable.  I my riba dosage daily is 1600.  Three in am, 4 at night.  My blood count is low, was lower a couple weeks ago, WBC down to 2.6 but cliimbed to 2.9 and is holding.  I am wondering the same as you, if the higher dosage is helpful.  I think they are testing again on the 30th...my cycle of 4 wk and 12 week check is a bit off.  It is interesting in any case.

Blessings,

Lee

[negative1]

Lee,
3 am and 4 pm would be 1400. That is the dose I was on.

[pixie]

Earl,

I am on week 14.  They tested at 6 weeks and I was undetectable.  I my riba dosage daily is 1600.  Three in am, 4 at night.  My blood count is low, was lower a couple weeks ago, WBC down to 2.6 but cliimbed to 2.9 and is holding.  I am wondering the same as you, if the higher dosage is helpful.  I think they are testing again on the 30th...my cycle of 4 wk and 12 week check is a bit off.  It is interesting in any case.

Blessings,

Lee

Can I ask your weight..?....Are you geno 1..?....

Here in the Uk we are fighting to get 4 week PCRs now...

Theres a school of thought also here the lower your Hb the better as the virus has a problem thriving...


Earl its so important to make sure you know the results of PCRs.....if your stlil detectable at 24 weeks you could try a switch of interferon. and longer tx time....

I will try and drop in more...just one week till my wedding...went shopping today as girlies do got myself something nice for jb...

[negative1]

Pix,
I think you mean Lee and not me. I have completed tx.

My weight was 265 lbs when I started tx and was on 1400 of riba.

No one ever took my weight when I went into get my blood work and had no appointments with my specialist during tx. In the first 8 weeks I lost 45 lbs and my riba was never adjusted for it.

My riba was cut down to 1000 though at week 40 due to mental sides.

Good luck with the wedding!

Earl

[Pancho and Lefty]

Lee,

I'm interested in the dosage/body weight, too. I'm doing 1200 and I started about 175-180 lbs. Still about there. They told me the dose was right. Hope I'm getting enough death porridge to kill this damn stuff.

Earl, thanks for the info--you posted while I was fumbling with the keyboard.

beginning VL 330K
4 wk PCR  18  (they used to call that und and my doc still is)
24 wk tx
middle of wk 8
gen 3a

[Lee]

lol..you are right Earl..1400...sorry about that...

Pix, Max,

I am geno 1, 160 lbs when I started.  I was not weighed at first, but later on they started to.

I hope that helps.  My viral count when I started was 11M.

Blessings,

Lee

[robin]

Hmmm....I was 110 pounds and started at 180 Pegasys and 1200 Riba. The sides from the riba were not fun and I can't imagine anyone being able to handle this type of self-treatment. That is one tough guy there. Keep your spirits high...robin

[Pancho and Lefty]

so much for the weight based dosage . . . .

there seem to be a lot of physicians just going through the motions of providing care

mine certainly is.. . ..