Length of Tx Formula

[Valtod]

The two most important questions each one of us faces are:
1) WHAT kind of treatment (Tx) do you need?
2) How LONG should it be?

A set of predictive factors - genotype, baseline viral load (VL), weight (BMI), liver damage, sex and race - can affect the initial decision for treatment. However, at this point the standard Tx is either Pegasys or PegIntron plus Ribavirin with weight-based dosing.

After the first injection, the first question is answered, the decision is made and most of us stick with it during the course of Tx. Now all the initial negative or positive predictive factors are conflated into a single variable - the speed of viral load (VL) decrease and the point when it becomes undetectable (UND).

You want to know what is your optimal length of Tx.
You don't want to extend Tx after it, if the chance of sustained virological response (SVR) won't improve.
Conversely, you don't want to stop Tx earlier, if the chance of relapse will increase.

If you are Genotype 1 on Pegasys/RBV weight-based, it seems there is a very simple formula for your optimal length of Tx. Here it is (where X is the week of UND):
Length of Tx = 3X + 12

If you're a rapid virological responder (RVR), UND at week 4, then your length of Tx is 24 weeks.
If you're not so lucky, for each additional week of delayed UND, add 3 weeks to your Tx.
UND=4, so Tx=24  - RVR
UND=8, so Tx=36  - EVR (early virological response)
UND=12, so Tx=48  - EVR
UND=16, so Tx=60  - DVR (delayed virological response)
UND=20, so Tx=72 - DVR

Of course, you need frequent and precise PCR tests - every 4 weeks preferably - to track your VL before you reach UND.

[Sincebirth]

Here is a link to the pdf of the graph that I described above

I have marked where the viral drop is and the corresponding SVR rates

http://rapidshare.com/files/18966653/Response_rates.pdf.html

[Valtod]

Jim, it seems now you have a better understanding of what I was trying to convey. Also, your questions and critique helped me to clarify and emphasize some crucial points of the model.

The main point of critique remains - as I recognized and explained earlier - the issue of "scope of applicability". Not the underlying assumptions or logic!

And, no, "a 60 year old black, stage 4 male" will remain outside of the scope of applicability. Also, I stated clearly the CURRENT "implicit constraints: only Caucasians included; lower average BMI and age than in similar USA studies; exclusion of 'difficult to treat' patients."

However, the scope of applicability CAN be widened further by achieving better and really optimal course of Tx (higher dosage, frequency, additional drugs) for the currently "excluded" - Ferenci's approach is indeed suboptimal for them. Then your "60 year old black, stage 4 male" WILL be drawn inside the circle of "applicability".

I believe the most important statement in all my responses is:
In a way, you can define "optimal Tx" as such that its length is a function ONLY of speed of viral clearance.

If you appreciate it, you'll see how the formula, based on the Ferenci study, can be generalized further and further. As I said many times already, there are 2 distinct steps:
1) Selecting optimal Tx
2) If this Tx is indeed optimal, then the length of Tx will depend ONLY on speed of viral clearance.

You agree yourself "that viral clearance trumps many pre-tx predictors". Well, the only leap of faith you have to make is that, even now with the current SOC, the viral clearance already trumps ALL pre-Tx predictors for majority of patients. And by improving (individualizing) Tx, the scope of applicability will grow and include even more 'difficult to cure' cases.

Finally, I'll touch on 2 other minor issues.

You wrote: "Help me here, I only see one assumption. The first three in the list with * are simply statements based on selected study data."

They're more important than you probably realize because they define 2 cornerstones of the model: 1) For each point of viral clearance, there exists a point of "saturation" for effective length of Tx, beyond which no increase in SVR will be achieved. 2) At least three such points (known from data) are needed for interpolating a reliable functional relation between initial viral clearance and length of Tx.

The numbers come from Ferenci but you can plug numbers from any other study, group of patients or form of Peg. In fact, I did exactly that when I varied the third point, producing different curves:
wk 4: (4,24); wk 12: (12,48); wk 20: (20,68) or (20,72) or (20,76)

So, as you can see, the assumptions are more fundamental than "simply statements based on selected study data."

The second issue is: "Personally I think Peg Intron is the stronger drug." I guess it's in response to my statement: "PegIntron clears much faster from the blood then Pegasys. For many years it's known to perform worse for HCV-1 high VL patients and twice weekly dosing was proposed."

Maybe it's not clear enough but I speak specifically for the WEEKLY viral kinetics of PegIntron vs. Pegasys. The fact that "PegIntron clears much faster from the blood then Pegasys" in its weekly cycle, I believe, is undisputed. That's why "twice weekly dosing was proposed" and I hope it'll become SOC.

On the other hand, once you achieve initial viral clearance and then reach ETR, at THAT point the average relapse ratio on PegIntron is often lower than Pegasys, according to different studies. So, yes, I would agree with you that PegIntron is probably the stronger drug. However, at its current SOC dosage, it seems its scope of applicability as optimal Tx is narrower than the Pegasys scope.

In Zeum study the RVR subset that reaches point of saturation at week 24 excludes VL >600,000. On the other hand, in Ferenci study the whole VL spectrum is included. As I stated earlier, I believe that the reason for it is NOT that Pegays is "stronger drug" but because PegIntron is suboptimally applied for significant segments of treated population.

And here's my hunch: if in two statistically similar RVR populations Pegasys (weekly) and PegIntron (twice weekly) are applied, the PegIntron group will have higher rate of SVR for the same Tx duration (24 weeks).

Thanks for the thoughtful dialogue!

[jmjm530]

As stated, in general I agree that viral clearance trumps many pre-tx predictors, but I'll go back to Ferenci versus Zeum as an example where it might not, at least for a shorter-course treatment. I'm also not convinced that blacks and high BMI's who RVR will have the same rate of SVR as skinny white's, but admittedly don't have any studies in front of me. But to Ferenci and Zeum again.

Val: Ferenci uses Pagasys, Zeum uses PegIntron. PegIntron clears much faster from the blood then Pegasys. For many years it's known to perform worse for HCV-1 high VL patients and twice weekly dosing was proposed.
-----------------------------
As you probably know, you can pull as many studies pro one peg versus the other, and not coincidentally the studies favoring one over the other are generally funded by or run by researchers affliated/sponsered by that particular peg. I consulted four well-know hepatologists. The ones that used Peg Intron and ran Peg Intron studies felt it superior and vice versa. I ended up using Pegasys because my tx doc uses it and is more familiar. Personally I think Peg Intron is the stronger drug. It also happens go be used by Dr. A. in NY, Dr. A in Boston, and I believe (not sure) Dr. S. in Miami. Not exactly slouches but arguably three of the best hepatologists in the country.

Val: Well, I find the implication "if not already published, it's probably not valid" a VERY weak argument.
------------------------
An extremely "WEAK argument" indeed, but I wasn't making argument, just being cautiously curious. That said, I don't find it "trivial" at all, as other formularizations such as the Drusano model have been published. I'm sure that if a trial researher believed as strongly in the formula as you did, then they would publish it. That's why I suggested you email it off. No slight intended here regardless of my admitted skepticism.

Va: However, I still don't understand why EXACTLY are you skeptical? If you accept (and understand) the 5 assumptions, the formula is almost self-evident.
-------------------
Help me here, I only see one assumptions. The first three in the list  with "*" are simply statements based on selected study data and the last appears more to do with how the forumula works. The only "assumption" I see are " Dosage, frequency and adherence are constant and consistent until end of Tx (ETR).

Cont..

[jmjm530]

Valtod: I now claim, based on Ferenci study and data, that the formula is relevant for the MAJORITY of the HCV-1 patients.And your intuitive skepticism is probably rooted in your personal circumstances - you're not part of this majority (the age factor)a
---------------------
My problem with your original statement had to do with it's global nature. If you're now saying it holds true for a "majority" of people then I have less of a problem.  

"If you are Genotype 1 on Pegasys/RBV weight-based, it seems there is a very simple formula for your optimal length of Tx. Here it is (where X is the week of UND):
Length of Tx = 3X + 12"

Just like to thank you again for your thoughts and diaglogue. I played around with formulas myself in trying to figure out my optimal treatment length so certainly not against formulas per say. I just feel that as useful as they are as a starting point,  they often need to be tweaked to the individual. I'm also not sure that a fat, black, 60 year old stage 4 male with low cholesterol, on a second round of treatment who RVRs -- has the same SVR rate as a skinny, white girl RVR who is stage 0 and has high cholesterol. I know the example is loaded but just to point out how many variables they are. And given the variables, would you really suggest the 60 year old black, stage 4 male on his second treatment shorten it to 24 weeks because of his RVR. I think for him a more reasonable choice would be to take it to 48 weeks.

All the best,

-- Jim

[Valtod]

SinceBirth offers another model, based on viral kinetics. It can be expressed in the following formula for the optimal length of Tx:
Y = X + 5W/L
Where:
X - Number of weeks before UND;
L - Log drop of the last VL slope before UND, which is assumed linear;
W - Length of this slope in weeks.

Let's call it "radical version" because later it's allowed to add 12 weeks to this date "to be sure".

Y = X + 5W/L + 12 ("conservative" version)

Let's test the conservative version for the most common case of 12 week responders (nor RVR), whose optimal length of Tx is uncontroversial 48 weeks. Let's also assume VL linear slope for 8 weeks before clearance (UND), starting at week4. That is:

X=12; L=8; Y=48;
Let's plug them in the formula:
48 = 12 + 5*8/L + 12, so L=40/24=5/3

So the VL at week 4 is 1 2/3 Log, which is 47 UI/mL.

So the "conservative" model requires VL<47 (!) at week 4 for responders by week 12, in order to allow them 48 weeks of Tx.

By the way, the "radical" version (without the additional 12 weeks "to be sure") demands even lower VL < 13 at week 4.

This all is quite absurd!

[Valtod]

Re: Ferenci vs. Zeum

Ferenci uses Pagasys, Zeum uses PegIntron. PegIntron clears much faster from the blood then Pegasys. For many years it's known to perform worse for HCV-1 high VL patients and twice weekly dosing was proposed.
http://www.natap.org/2004/DDW/ddw_04.htm

With suboptimal Tx, Zeum had to add the constraint for low VL in order to achieve the same results as Ferenci. If Zeum used twice weekly PegIntron, he'd probably be able to include the whole spectrum of VL patients into the 24 week optimal length of Tx. Or it may be 27 weeks or 34 weeks. Only the experiments will provide the data where exactly is the optimal length of Tx for a particular (hopefully optimal) dosage and frequency. What IS important is that such optimal length exists.

By the way, Pegasys studies face similar problems as Zeum when they use fixed doses of RBV. In these cases the BMI remain important predictive factor for SVR. If you want to treat RVR with low fixed doses of RBV and still achieve optimal Tx response at week 24, you had to add the constraint for BMI < 25. However, when Ferenci went for weight-based dosing, the BMI variable conflated into the speed of viral response.

Both Ferenci and Zeum studies have some other implicit constraints: only Caucasians included; lower average BMI and age than in similar USA studies; exclusion of "difficult to treat" patients.

Still, using Pegasys/RBV weight-based, Ferenci succeeds to determine optimal length of Tx ("saturartion"), based only on ONE variable - speed of viral clearance (UND) - for quite broad segment of HCV-1 patients.

As  I wrote in the original post: "A set of predictive factors - genotype, baseline viral load (VL), weight (BMI), liver damage, sex and race - can affect the INITIAL decision for treatment." But once this decision is made - hopefully CORECTLY - then all these factors conflate and the length of Tx depends ONLY on the speed of viral clearance (UND).

High BMI can be countered with higher dosage of RBV (and probably Pegasys), high VL and liver damage - with higher frequency of injections (ever 5 or 4 days, or twice weekly). Adding protease inhibitors will further "equalize" the initial factors. Then only the viral kinetics will remain to play role in determining the optimal length of Tx for almost all patients.

In a way, you can define "optimal Tx" as such that its length is a function ONLY of speed of viral clearance.

So in the Zeum study his PegIntron once weekly is optimal Tx for all with low VL. For high VL such choice and dosage of drugs is suboptimal.

Once again, please read the 5 assumptions for my model and formula! If, and only IF, they're applicable to given set of patients, then the formula correctly gives their optimal length of Tx.

Ferenci study is interesting and important because it shows that, even with the current standard of Tx, it seems that the MAJORITY of HCV-1 patients can find the 5 assumptions applicable and reach their optimal length of Tx, calculated by a simple linear formula.

On the other hand, if you do not find the 5 assumptions applicable (and acceptable) for your group (or yourself), obliviously the model and the formula won't apply. This usually means you're in the upper 10% or 20% most "difficult to cure" patients.

If you're well in the constraints of the Ferenci study but you experiment and change dosage, frequency and adherence to the drugs during Tx (especially before viral clearance - UND), the formula will NOT work either.

[Valtod]

Space, you're double dosing, so the formula doesn't apply to you. But with EVERYTHING else equal, you should probably need shorter treatment than someone like you on standard weight-based Tx (Ferenci study).

Wyn, if I were you I'd extend to 72 weeks. If you don't clear by week 16, and especially if you reach plateau, chances of relapse are high. I just read somewhere that, with clearance AFTER week 12 on standard Tx for 48 weeks, the NPV (negative predictive value) is 81-90%. That means that if you predict that someone in this subgroup won't achieve SVR, you'll be right for 9 out of 10 patients. Again, this is for 48 weeks - so 72 weeks is really the only way to go in your case. Even if your chance of SVR is small, 24 additional weeks will improve it. And for sure it's higher than 0 :-)

It's interesting how all the participants in this thread - Jim, FLGuy, NYGirl, Space, Wyn, myself - are not actually "average" HCV-1 crowd on standard Tx for whom the formula would apply :-)

[Valtod]

Re: Formula

Jim: "Was this formula posted somewhere in a study or is this your extrapolation based on the studies you posted? If it's your extrapolation, I do not have the math background to critique but would think that if valid it would have been published already."

-------------------

Well, I find the implication "if not already published, it's probably not valid" a VERY weak argument.

One possible reason that it's not published already may be that it's way too trivial and self-evident for serious researchers. I find hard to believe that Ferenci and others didn't see the linear (or close to linear) relation between time of blood viral clearance and optimal length of Tx. However, serious researches wouldn't bother to state self-evident conclusions. Their peers are supposed to make them themselves, based on the provided data and initial analysis.

On the other hand, such "ready-to-use" formula may have some utility for patients and practicing GIs when trying to rely on something more than a "gut feeling" for optimizing the length of Tx.

-------------------

Jim: "That said, why don't you email it off to some of the authors for feedback. Admittedly I'm skeptical."

-------------------

I already discussed it with a HCV researcher and my local GI. They both didn't find anything wrong with it. Actually, I was under the impression that there was nothing in the model that was particularly unexpected or hard to swallow.

I'll probably formalize the idea better and send it to other HCV researchers.

However, I still don't understand why EXACTLY are you skeptical? If you accept (and understand) the 5 assumptions, the formula is almost self-evident. On the other hand, without the assumptions, the formula has no claim for validity anyway.

If you think that exactly one line can be drawn through any point not on a given line parallel to the given line, you live in a Euclidean universe. On the other hand, if you do not accept such an assumption, you are in some Lobachevskian world. They're both true and consistent. You can agree, or disagree with the underlying assumption but not with the models per se. You can also discuss their relevance to a set of everyday problems you personally try to solve. You can say: "In 9 out of 10 problems that I face, I can go by Euclidean rules. But there some extreme situations, for which these rules are too simplistic."

Since I can always show some group, for which the 5 assumption apply and the formula is true, the only criticism one can seriously bring is about the "scope of applicability".

I now claim, based on Ferenci study and data, that the formula is relevant for the MAJORITY of the HCV-1 patients.

And your intuitive skepticism is probably rooted in your personal circumstances - you're not part of this majority (the age factor) and your treatment approach (induction with double dosing) negates the 4th assumption (constant dosage and adherence), so the model and formula does not apply to you personally.

As a token of solidarity, I'll admit that that the formula does not apply to me either - I also experimented with my drugs dosage and frequency in the most important weeks. However, the fact that the Earth's curvature is of life and death importance for a bunch of NASA engineers, doesn't mean a thing for the majority of humanity walking and driving their cars on "flat" surface.

For all of them the sum of the angles in every triangle is 180 degrees :-)

[Sincebirth]

I have looked into the viral kinetics a bit and have concluded the best way to determine optimal treatment length is to plot your pcr tests on a log scale graph.  To explain this let me start with how the viral kinetics of this disease works.

The viral kinetics of HCV goes something like this:

There are main 2 distinct slopes of viral decay which are the following:

1)  Initial drop slope---This slope happens only a few days after first injection before the next slope comes into play (Usually less than 1 week).  It is due to the direct antiviral effect of IFN.  And can be anywhere from 0 to 2 logs of drop.

2) Second slope drop---This is usually linear along the log scale.  Occurs after the first few days of tx.  This stage viral reduction is usually represented by a logarithmic decay of the viral load and is typically linear along the log graph. This slope along with how long you treat will ultimately determine your chances of success. I think the slope of this line is due to your body's ability to kill the infected hepatocytes and this can range from individual to individual.

This second slope is the one you want to graph.

So ultimately you would need a data point at the following
week 0 (before tx)
week 1.  (to determine 1st slope)
Then some data point to gauge slope 2, I would opt for a few data points to determine trend lines  -  test at week 2, 4, & 8 to get data points.  

Extrapolate this second slope until the line crosses 0.00001 IU/ml.

Why 0.00001 IU/ml?

To get a sustain response you need to drop you viral count to nearly zero. NOT THE VIRAL COUNT IN YOUR BLOOD tests which only measure a mere fraction of the amount of plasma in your body, but you whole body.

The amount of virus detected in your PCR represents a small fraction (1/10,000) of the viral copies in your total body. So say you have 9 copies (which is undetectable with a very sensitive test) you could have approx. 9 X 10,000 or 90,000 copies of virus in your system. That 90,000 needs to get pretty close to zero to get a sustained response. You need another 4 to 5 log drop of viral load to be clear.

So hypothetically speaking, the sensitivity of a PCR test to actually tell you if you are clear of the virus would in theory be 0.00001 IU/ml.

So somebody with a starting viral load of 1,000,000 would need an 11 log reduction to clear the virus.

IF you plot this extrapolated pcr line on the y-axis and time in weeks on the x-axis, you will know when you are theoretically clear.  I would add at least 12 weeks to this date to be sure.

I have done this with my results and plotted many results from the test studies that I have read about.  And they ALL correspond to the data very well.  

[Valtod]

Re: biopsy predicting relapse/SVR

No, I don't have official "studies or references to the researchers using viral material in a biopsy sample to predict relapse". But I know they do retroactive analyses of biopsy specimen in relation to post-Tx SVR in Miami and Gainesville. And if they do it there, we can assume they do at other places. At this point, they don't have clinical studies dealing with it. Again, these are "retroactive analyses but very promising", I was told. I asked if they can biopsy me near the end of Tx, but I was told "there is no protocol for it". So, basically, they work with biopsy specimen already collected and cross-check if it happens to come from people during or post-Tx.

Again, all this was related to me in a conversation and my understanding was similar to yours: "If your biopsy PCR is negative, your chance for relapse is close to 0."

On the other hand, I also know that "Castillo and colleagues reported that HCV may continue to replicate in the livers of sustained responders."
http://www.hcvadvocate.org/news/newsRev/2006/HJR-3.22.html
Unfortunately, I wasn't thinking fast enough to ask about the apparent contradiction.

[dointime]

This is great stuff.  Thank you for posting.  I've been trying to get my head around just this subject (the VL slope, shape, and what it can tell us) but with a lot less success than you've had.  I appreciate how you backed your data up from studies done.  Well done.
  
dointime.

[jmjm530]

Valtod: If A and B get UND at the same time, they have the SAME optimal length of Tx. All initial predictive factors conflate into a single variable - week of UND.
-------------------------
About a year and a half ago, I made a statement here that a hepatologist I consulted with said "RVR trumps all" in regards to SVR. That's basically what you're saying above. That said, he may have had one or two caveats like being non-cirrhotic. In spite of my RVR, the consulting hepatologist still wanted me to treat for 48 weeks.

My treating hepatologist disagreed based on his clinical experience and wanted me to extend. He challenged some of the studies as not being representative of my age and level of fibrosis, and in fact I could not find studies with a meaningful enough subset of older stage 3's with RVRs to compare with. I ended up compromising and treated 54 weeks. Would I have been SVR with 30 weeks of treatment as your formula suggests or 42 weeks of treatment as Drusano suggests? Of course I'll never know, but not one of the five hepatologists I consulted with wanted me to shorten treatment, and while the word here might seem overused, these were all "name" hepatologists who are well respected. For whatever reason, some of these studies were not persuasive enough for them to shorten my treatment given my stats.

[wyntre9]

I just want to make sure I understand your information with regards to my situation.

According to the studies you reference, if I don't reach UND until week 20, with a genotype 1A, then I should extend treatment to 72 weeks.  

Is that right?

And, according to your model, would my SVR rates be approximately 29% or 50%?

Thanks for your comments.

Wyntre

(I'm trying to digest this but I'm in the scientifically challenged sub group.)

  :)

[FlGuy]

Thanks for the lucid info. I'll spend some time digesting it.  Understanding mildly complex data is not my forte' these days, takes a while to sink in.  I need to turn it into a picture.

[nygirl7]

According to the studies you reference, if I don't reach UND until week 20, with a genotype 1A, then I should extend treatment to 72 weeks.
--------------

Exactly.  That was what happened to me in my situation and with all the research I could gather together and getting a second opinion from Dr. Ira Jacobson who was lead investigator of the Berg study agreed would give me the most optimistic chances of SVR.

Still: for those of us who don't reach UND until after 12 but before 24...chances aren't so wonderful but this gives us roughly a 1/3 relapse rate instead of a 1/2 chance or relapse.  To me that was big and worth the trouble.

(Plus I am 1A and also 1B and since I would have been UND at week 4 by older tests but then had an exact count in the 400s - week 4, 8, 12 - apparently I have some resistant mutants that were hard to crush.  So I knew I had no choice but to try this if my goal was to get to SVR)

[jmjm530]

There are several studies that suggest extending to 72 weeks if detectible at week 12 but non-detectible at week 24. The problem, however, is that some of the studies did not use weight-based ribavirin which just about all geno 1's are on these days. Keep in mind that these studies are guidelines and not cut and dry formulas. In addition, other considerations might enter into the extending equation such as how much liver damage you have. For example, some with little or no liver damage may feel it's not worth subjecting themselves to 72 weeks of the treatment drugs. In those cases, a better choice might be to stop treatment.

-- Jim

[jmjm530]

Jim: But assuming for a moment this method is valid, my understanding is that a negative biopsy PCR (NBP)
would exclude relapse but a positive biopsy PCR (PBP)would not necessarily exclude SVR.
------------------
I'd like to change the first part to "it might make sense that NBP would exclude relapse...

I'm changing it because how do we know it does until we see some studies.

But the more important part is your statement "If there's a viral material in the biopsy sample, that means the patient will relapse, so the Tx continues"

And again, we know that SVRs may have some viral material in their biopsy samples so that fact alone doesn't appear to mean the patient will relapse.

[wyntre9]

Thank you, both for the feedback.

I've pretty much decided, as NYG did, that with an UND before 24 (going for labs today - week 18 - 16 week was VL 90 so I think I must be UND now but will post results when I get them)) I will continue TX as I've arranged for time in my life to do that now.

Who knows what will happen in the future?

I will take a 30% chance over 0 chance, especially since I've already done 4 months.

Then, if it doesn't work and I relapse, I'll take it from there.

In the meantime, if the SX get too overwhelming, I suppose I will consider stopping.

But not to take the chance that I might clear, in light of all the other hoops i've jumped through, and in light of the fact that I (apparently) fall within current SOC guidelines, wouldn't make sense to me.

I've also read that the earlier you treat and the less your damage the better the chance of SVR.

And one thing that stuck out in Valtod's explanation was the trend toward individualized treatment.  That's what they do with allergy treatment.  I know that appraoch worked for me there and it's also an immuno-suprressant condition.

As far as weight-based riba, I'm on 1,000 mg and I weigh 135.

NYG - have you gone for the follow-up test yet?

Thanks again, guys, for your advice.

wyntre

[spcecst2]

These are all interesting post but let me riddle you this?
If an individual double doses and gets RVR less than 5 at week four, are their chances of SVR just as high as someone who got RVR less than 5 at week four on the standard dose?
If an individual who relapse

[jmjm530]

Not sure if you were making a point or asking a question, but if you are raising a point, it's a good one. Just too many variables for hard and fast rules/formulas. That doesn't mean we shouldn't be guided by studies but it does mean we have to be careful over generalizing. Anyway, hope your treatment is going well. Any viral load tests yet? Certainly an RVR is the best to hope for regardless of the scenario, but in the case of someone re-treating with significant liver damage, I wouldn't rush into a shortened, 24-week treatment based on any studies I've looked at.

-- Jim

[FlGuy]

Not sure if there's a code message in there. I don't think you are in week 4 yet - maybe so.  With the DD and riba+, I'm guessing you mabe be shooting for a 2 week pcr?  Anything?  Similar message to you above.

[spcecst2]

I am just wondering how much the treatment can do, or does so much depend on the individual

[jmjm530]

That's really the 64 dollar question. Is it the immune systems, a genetic component, the strain of virus itself, a combination, something else. Once they know exactly why some people respond and others don't they will be further along in research than they are now. What they do know, however, is that certain things like double-dosing and higher ribavirin can help the response rates in general.

-- Jim

[jmjm530]

Don't want to leave the impression that anyone who is detectible at week 12 has a good chance of SVR without extending -- weight based riba or not. My comments on weight-based riba were to the SVR projections used in the Berg study that used fixed-dose ribavirin. The projected SVR rates at both 48 and 72 weeks might have been higher had they used weight-based ribavirn.  http://gastroenterology.jwatch.org/cgi/content/full/2006/825/1