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polymerase vs protease inhibitors

by rossrad, Jan 19, 2006 12:00AM
Hi Folks,   Sorry I haven't been posting.  Been gone and off on other tangents a lot recently.
I am starting to get some buzz from my connections for clinical trials. They haven't yet told me what's up, but I can tell that they are gearing up for something that I would qualify for as a non responder.   They know I will only do protease inhibitors because of 2 failed attempts with combo.  The only protease inhibitor trials I know of in my area are sch503034 and vx950.  Sch503034 will not go into phase 3 until much later this year and vx950 is only doing tx naive.  So, as best I can tell that leaves only the polymerase inhibitor nm283.  I haven't been following this drug.  The best info I can find on it was just released from a phase 2b showing good results, but nothing like the early reports on vx950 and sch503034.  
Since it seems I will likely be invited to a trial of nm283, does anyone have some advice on choosing this route instead of waiting a year for one of the protease inhibitors.  I would jump on the chance for a trial with one of the protease inhibitors, but I don't know much about nm283, so I'm not sure.
I have a 0-1 biopsy, but am quite sick with the HCV.  I cannot do another failed attempt for several reasons.  I do appreciate any and all feedback on choosing nm283 soon, instead of waiting for the others.

Thanks much,

Rossman
Member Comments (36)

by cuteus, Jan 19, 2006 12:00AM
there are a couple of members here who are on NM and are reporting excellent response with it. At least one of them is very happy to have finally achieve a negative PCR.  Maybe he/she will check in this wk.
perhaps you can add a comment with a title NM283 to call the  attention of these members. I can't remember their monickers. It did sound like a good drug for non responders.

by TnHepGuy_, Jan 19, 2006 12:00AM
To: rossrad
Here's some info:

- data from week #12

<a href="http://www.natap.org/2005/AASLD/aasld_42.htm">NM283 +Pegasys for Nonresponders: phase II 12 weeks</a>


- data from week #24

<a href="http://biz.yahoo.com/prnews/051214/new020.html?.v=33">Partial 24-Week Data Demonstrate Valopicitabine (NM283) Combined with Pegylated Interferon Continues to Produce Greater Viral Suppression in Hepatitis C Treatment-Refractory Patients Compared to Retreatment with Ribavirin Plus Pegylated Interferon
</a>

(from the study):

"<i>At Week 24, mean HCV RNA reductions in the two high-dose arms of valopicitabine plus pegylated interferon were 3.01 log10 and 3.32 log10, with 11 percent and 25 percent of patients achieving undetectable levels of virus. In comparison, patients in the pegylated interferon plus ribavirin retreatment control arm showed a mean HCV RNA reduction of 2.31 log10, with 19 percent of patients achieving undetectable levels of virus.</i>"


Halfway through tx and there's only a 6% increase in serum clearance vs. re-tx'ing with current tx, and a 25% clearance overall. Not-so-hot odds, especially given that there's still another 24 weeks of tx'ing left - and 6 months after that to reach SVR status. Makes you wonder what that 25% figure will drop down to 50 weeks on (i.e. - when the SVR data comes in).


Your tx or wait decision should include the possibility that future trials of these other drugs (assuming they would even be in your geographic region) might only want tx-naive patients, in which case NM238 may be your best/only bet for the near-term (assuming you are that much in want of re-treatment).


TnHepGuy

by rossrad, Jan 19, 2006 12:00AM
Thanks everyone.  Yea, I'm not sure if having another failed attempt on my record could preclude me from future tx possibilities. I doubt anyone could answer that ahead of time.  But, that is one variable to consider.  I must make a better decision this time.  There are several reasons to not have another failed attempt at tx and being precluded from future tx is one I need to consider.
Thanks for the tip about another post addressing nm283 directly.  I will do that soon if not many responses.
Thanks for the link on the nm283 phase 2 trial.  I too saw those 24 week stats and thought it didn't look great.  Only a little better than ribo.  And I cannot take that chance.  I cannot take a chance on only a 6% improvement.  But, I've also read that the nm283 is showing a potentiated response with continued tx and this is the reason they extended the study up to 48 weeks.  With Ribo, the tx has done it's best by week 24.  Apparently not so with nm283. I'll check out the link.  
Thanks everyone for the input.  This is what I'm after; help making the best decision.

by jmjm530, Jan 19, 2006 12:00AM
To: Landfill re: comments in thread below
One definition of EVR (early viral response)is non-detectible or at least a 2-log drop by week 12. The same at week 24 is not considered EVR. RVR (rapid viral response)is the same at an earlier point in time, usually week 4.

Regarding testing -- the biggest viral load drop is right after the shot and in fact the biggest drop during treatment is usually during the first 24-hours after your first shot of Peg. For that reason viral load is usually measured on a "trough" day to get a conservative estimate. The trough day would be on day 6 or even day 7, right before the next shot.

Frequent PCR testing can effect the outcome of treatment in the sense that it gives doctors more information regarding viral response so that they can then tailor dosage/length if they want. It can also save someone who isn't responding from unecessary exposure to the treatment drugs.

Be well.

-- Jim

by rudy222, Jan 19, 2006 12:00AM
Peg/283 is infinitely easier to tolerate than peg + riba.  It took Nuepogen and Epoetin to get me through peg/riba.  
Rudy

by jmjm530, Jan 19, 2006 12:00AM
To: Rock
Evening. How's treatment going? Are you able to hold your weight on your extremely healthy diet? How about your taste buds? Mine were altered (and still are) from the treatment drugs and many of the healthy foods I liked I can't eat now. Did you find a flax substitute with your riba?

-- Jim

by roxxiroo, Jan 19, 2006 12:00AM
To: Vegas

vegas, I am in the Fibroscan study at Duke. They did it two months after my bx. I was there getting a physical in order to start the Ideal Study. They approached me about the Fibroscan study and said that it was a one time scan that would take just a few minutes. I was eager to see the results and  help if this meant by comparing to current biopsys, that one day the adjustments in the reading comparisons would help this become an available test to all. I can tell you it was a dream compared to the bx. I know everyone says they don't hurt, and it it true the biopsy does not hurt. All the deep needle sticks in my side to numb me was not fun though. I am very lucky in that I live ten minutes from Duke. I have great insurance, but I chose the Ideal Study and have no regrets. I have felt well taken care of in the study. By the way I just turned 57 a couple of days after Christmas. I still feel young enough that I was not very concerned about treating. I may be keeping my head in the sand, but I just try not to worry about what can happen. My partner pulled out a gratitude journal that I had tried to keep in 1997. I only kept it for the month of January. My Jan. 22 entry was "I am grateful for the energy to floss and brush my teeth tonight." I knew I had been tired the last few years....even though I stayed active... but that entry going back to '97 surprised me.

by vegas777, Jan 19, 2006 12:00AM
To: rox
did they give you a print out of the results of the fibroscan?  intersting about your journal!

by NYgirl, Jan 19, 2006 12:00AM
To: Question
Sorry to jump...but I don't want to tell her the wrong info and she keeps asking if I know anything

Question:

My mom has had a very high ALP (Alkaline Phosphatase sp?) number for many years and totally ignored it. I am trying to convince her that that is like ignoring my ALT or AST. They want her to bx but she wont now thinking it's "nothing...been this way 18 years".

Does anybody have a clue what it can mean? I read possible bone or liver disease or tumor......I know she is just going to keep ignoring it. I don't understand why people do that ... I've learned my lesson the hard way. But on the offhand chance I can be useful and get her to the bx (she took me to mine after all)...anytihng would help.

I love my ((Mommy)) she had MANY transfusions in 1990s or so so I'm concerned for her.

Any input would be appreciated.

by NYgirl, Jan 19, 2006 12:00AM
To: Low White Counts
Are there any symptoms of the low whites?  When the doctor said today "well your whites have finally started to drop" (at 1000 now) he said it oddly like it was so expected

I don't really know what it means or what to look for if there is a side.  I know if it goes down to 500 he will put me on Neupogen.  That is all that I KNOW - and you know I'm obsessive about not knowing things.

I've only gone the hgb route and I know that all too well!  But now that I'm a 12.5 I'm feeling just fine.

by landfill, Jan 19, 2006 12:00AM
To: Jim
Hi Jim,
Lessee...

2 logs or better @ wk12 and undetectable @ wk24 is the only EVR I know of.  What are the others?

My minimum PCR strategy for gen1 is wk12, wk24 & wk48.  If I feel extravagant, I'd get one at wk4 to check for RVR and one around wk35 to check for breakthrough. The cheapest (highest threshold) PCRs will do.  If my hypothetical patient got my 3 cheap tests and you added multiple high sensitivity tests, what results would lead you to change the tx? - Bob

by cougareyes, Jan 19, 2006 12:00AM
To: nygirl
WBC at 1000, were you talking about absolute neutrophils?, because your reference to 500 is what most doctors lean toward now( some 750, some lower than 500). These being too low could open one up to infections, the most common is an upper respiratory infection. Also cuts or anything that requires own body to help heal it gets compromised when your absolute neutrophils gets too low. Just like any other labs these go up and down, the interferon is the culprit here.
I'm not familiar with ASP, but like you I am now aware to get things checked out when something is out of whack. Hopefully you can get your Mom to get to the bottom of it.   Peace

by jmjm530, Jan 19, 2006 12:00AM
To: Land
Hi Land,

Lessee LOL..

Seriously, I read your post to define EVR as non-detectible at week 24, but yes, what you say here, is correct -- a two-log or better drop at week 12 is EVR. Better of course is being non-detectible at week 12.

One reason the more sensitive tests are better is because non-detectible is more and more being defined by the studies as at least under 50 IU/ml. So, if your test has a sensitivity of 600 IU/ml, you could test negative but still be detectible, if say your viral load was 400 IU/ml.

So, using the Drusano model (treat 36 weeks past non-detectible) using a less sensitive test could result in a different tx length. As another example, if you went non-detectible at week 4, and were having a very difficult period with sides at week 4, you would have more information to make a decision regarding the risks/rewards of continuing on. Lastly, multiple PCR's have the added benefit of more or less guaranteeing you that you were consistently negative throughout treatment. It's possible some people have a viral breakthrough -- then a reversal -- mid treatment and don't know it. If they had the added information, they might treat longer.

That said, testing at week 12, 24 and 48 is pretty standard with the 4-week PCR becoming more popular. I'd simply recommend that as long as you're getting stuck with the needle, why not get the most sensitive test available?

It's a bit past my bedtime, so I hope this is making some sense.

Take care and thanks for asking.
-- Jim

by jmjm530, Jan 19, 2006 12:00AM
To: Land
That should read "a difficult period with sides at week 40" in third paragraph...

by jmjm530, Jan 19, 2006 12:00AM
To: NY
My ANC (absolute neutrophils) have been as low as 320. My med team rarely uses Neupogen and only if it drops to around 200. BTW they are VERY agressive, just not with this drug. Everytime I got below 500, I emailed them and they told me to relax, that it will probably bounce back it -- that the low count was probably caused by an infection. They were right. My ANC has "bounced" around from 320 to 1700 often in a matter of weeks. Currently it's around 1200. My opinion -- and it's only that -- is that most doctors are too slow on the draw with Procrit but too fast on the draw with Neupogen. Again, unlike with Hgb, ANC can reverse itself very quickly without a rescue drug. Your milage may vary but I certainly wouldn't be concerned at ANC 1000.

-- Jim

by stc1993, Jan 19, 2006 12:00AM
Here is a study I haven't ever heard of before. I thought some of you might like to read about it.

http://www.romark.com/index.php/media_center/press_releases/35.html

Monte

by GoofyDad, Jan 20, 2006 12:00AM
To: Kalio
Awww, c'mon Kalio, no need to get your knickers in a knot - I meant no harm...

You say: <i>I didn't say risks should not be presented openly and honestly
anywhere in my post!</i>

I suppose I could go down the tit-for-tat road and point out that nowhere in my post did I say that you said that in your post. But endlessly listing things we didn't say would probably become counter productive, sooner rather than later :) :)

You say:<i> nor did I say that fear of treatment is
overblown on this board, <b>I said to do so wouldn't be prudent</b>.</i>

Respectfully, I didn't find the words <i>wouldn't be prudent</i> in your post. I did find the quote: <i>...to overblow the fear of lingering long term side effects <b>scares</b> people off from treating</i>

Absent of a conditional modifier such as <i>could</i>, <i>would</i>, or <i>might</i>, I took <b>scares</b>
to imply people are actively being scared off of treating. If that was not your message, my mistake. And since I seem to have missinterpreted your message, where such statements (that didn't occur) were (not) made becomes somewhat moot.

<i>I don't understand what it is you are trying to disagree with me on.</i>

I'm really not. Simply trying to give another point of view. As I said, no harm intended. Sorry that I've offended.

Take care my friend.

by NYgirl, Jan 20, 2006 12:00AM
To: Goofy/Kalio
I think that there ARE people who come in and read and DO get scared from treating.  I know one person who is now petrified of Riba and won't treat because of all they have read.

BUT...like any message board - this board is a hodgepodge of ALL thoughts and opinions and nothing more. Experiences are all different and presented by what the opinion is.

Hopefully we are a good enough example of the positivity of treatment - and can encourage people who need to.

I would never want to turn anyone OFF of tx - people need to decide either way for themselves and we can only give our experiences and advice and opinion on that.

Yeah..we put poisons IN  but hopefully they are killing the potentially deadly virus that is already there.

by jmjm530, Jan 20, 2006 12:00AM
To: NY and All
NY said:I would never want to turn anyone OFF of tx - people need to decide either way for themselves and we can only give our experiences and advice and opinion on that.
---------------------------------------------------

Can't agree more on that people need to decide for themselves. However, we have to keep in mind that agressively shepherding people toward treatment who may have other options, is as risky as turning people off treatment who may need it.

While some will disagree, my take is that MH, compared to other boards, has a pro-treatment bias in the sense that tx sides/risks are minimized in the risk/reward tx equation.

Hopefully, those making treatment decisions will carefully read both sets of opinions here, do their own independent research, visit other hep c discusion groups for their perspective --  and of utmost importance -- find the right doctor (preferably a liver specialist (hepatologist) -- who can help put everything together, and guide them toward the right decision for that particular individual.

-- Jim

by NYgirl, Jan 20, 2006 12:00AM
To: Jim
See I think that people come in to the forums with pretty much ONE thing on their minds - HOW MUCH IS THE SIDE EFFECTS GOING TO HURT ME?????  I know it seems when new people come in my take is that is their first and biggest concern.

What I was trying to SAY is that I would not want to turn anybody off to trying tx based on my whining (ah the anemia is horrible! ah the Ribarash drives me nuts!!!).  While I do feel we NEED a place to complain to those who UNDERSTAND...I try to remember that others might see it as IMPOSSIBLE to deal with and choose not to based on my comments.

So I try to remain upbeat about it.  It is everyones personal decision in the end.  I just don't want to be the cause of mistakenly having anyone think it's not worth trying...just because it IS inconvenient at times.

by jmjm530, Jan 20, 2006 12:00AM
To: Kalio
Briefly regarding doctors generally recommending geno 2's and 3's treating...

It's the risk/reward equation which basically is at the heart of all medical decisions.

Geno 2's and 3's have an 80% chance of being cured with only 24 weeks of treatment. Therefore their chance of reward (SVR) is greater and their risk (exposure to tx drugs) is less.

Geno 1's, on the other hand, have let's say 40-45% chance of being cured with 48 weeks of treatment. Their chance of reward (SVR) is less and their risk (exposure to tx drugs) is more.

I really think it's only that and to me it makes a lot of sense. I agree that hep c patients should be given all options when diagnosed but a good doctor also has an obligation to explain the options in terms of risk/reward based on his/her knowledge, available studies, and personal clinical findings.

--Jim

by cuteus, Jan 20, 2006 12:00AM
we are comparing tx efficacy with tx adverse events, not the same animal, different markings. The study that involved 500 subjects stated that the rate of events was the same in both the 48 wks and 72 wks tx groups. Nothing was said as to efficacy.

by jmjm530, Jan 20, 2006 12:00AM
To: Cuteus
From one armchair clinician to another with way too much time on our hands :) --

I was referring the fact that one of the conclusions was "superior safety" with the short-course treatment and not making a case for or against it in terms of efficacy -- the study does that for itself. :) BTW when Googling recently to try and pull the study up, I noticed a couple of trials -- not Italians -- not French -- not Spanish -- but AMERICAN trials. So hopefully, more data on shorter treatment courses will be available one of these days.

by GoofyDad, Jan 20, 2006 12:00AM
To: Andy
<i>I find this thread very amusing</i>

And I find your pompous arogance pretty amusing too. Between the two of us, we've got a veritable comedy fest going on! Let's enjoy it while it lasts!

<i>ensure that their Doc fully <a href="http://wordnet.princeton.edu/perl/webwn?s=abridge">abridge</a> them of the risks</i>

Thats the exact problem I've been trying to discuss.

<i>The sucess rate will either be 100%, or 0%....anythng else [is] fluff. </i>

Great, so we are to embark upon this treatment not considering probale outcomes, but rather based on a "might work, might not" assessment?

<i>There are a few studies that may suggest this or that, but at the end of the day, each person is an individual and thus using these abstracts to try to predict success or the lack of success is a fool’s paradise.
</i>

Excellent. Age old scientific process redefined by our own Edgewater Andy. This is indeed a great day for mankind.

<i>I trust some with their arm chair clinical opinions would keep this in mind </i>

Whatever, Dude. Physician, heal thyself.

by cuteus, Jan 20, 2006 12:00AM
it is about time we get with the program. Salaries and trial subjetcs  re-imbursement must be lower in the old country.


I like playing elitist medical wanna be, I have a couple of lifelines I can use too.

by jmjm530, Jan 20, 2006 12:00AM
To: Goofy/Cuteus
Goof: If your cognitive function has decreased on treatment treatment as you suggest, it must have been pretty scary good pre-tx. I didn't even know where to begin with that last post after I got to the "The sucess rate will either be 100%, or 0%. That I can guarantee." Boy, if that's what any of my doctors told me I'd be out the door in a second.

Cuteus: You can always poll the audience.

by andyarundel, Jan 20, 2006 12:00AM
To: goofydad
Oh well, intolerant one, the reality is most know the outcomes, and no doubt can cite them in their sleep. Pompous and arogant, is close to the only opinion that may have any relation to anything. I would suggest that I may be 48% arrogant and close to 28% pompous, but then again only on days when the sun is shining. My next comment I will reduce in scope while retaining the essential elements or abridge for your reading pleasure.

I would check your depends as they seem a mite wet.

by cougareyes, Jan 20, 2006 12:00AM
Is this "American Idol" or "Survivor". Just wondering as it may or may not influence my vote. This I can be either 100% or 0% sure of.   Peace

by andyarundel, Jan 20, 2006 12:00AM
To: jmjm
Zero or one hundred percent is the only medically proven effect from interferon treatments to date. If you are suggesting, and I will use your "cure" word for effect, that one can achieve any other result, as one may be 38% cured, or achieve a 68% SVR. Please by all means enlighten us.

by cougareyes, Jan 20, 2006 12:00AM
People should be scared of treatment, very scared. Because my QOL had suffered tremendeously and I was having classic symptoms of advanced liver disease, I felt I had to give tx a shot. Otherwise TX scares me more than HCV, just my personal opinion.    Peace

by GoofyDad, Jan 20, 2006 12:00AM
I hesitate to say this, but I think ecconomic costs must be recognized too. My doc talks about this openly, and I appreciate his candor. When we speak of me treating for 48 vs. 24 weeks, there is a significant ecconomic differential between the two, and it would be irresponsible not to consider it.

Most of us use insurance to pay for our treatments. Insurance funds are a means of pooling and sharing risks across a population. The funds must be spent judiciously, or in addition to escalating insurance premiums, we risk insolvency of the fund. Meaning no more insurance for the membership.

Back to my case, between the primary and support drugs I'm on, my treatment costs are running somewhere around $2,500 a week. Extending my treatment by 24 weeks carries a significant ecconomic burden. I believe it would be irresponsible for the Doc not to consider that in his decision making process.

by cougareyes, Jan 20, 2006 12:00AM
To: HCC
Most report the stats that 5-20% of HCV sufferers will advance to cirrohis. And out of these 5-20%, 1-5% will go on to develope HCC. My math isn't that great today but overall that means about 5 out of every 10,000 to about 20 out of 10,000. The average age of these HCC sufferers are just about 8 years less than the average lifespan today. Scare tactics work on both sides.     Peace

by cuteus, Jan 20, 2006 12:00AM
members stating their personal experiences and those of the folks with similar experiences of mild to moderate side effects on tx, should not be considered "minimizing tx side effects". They are stating a fact as it pertains to them. If it is to be considered "minimizing", then folks stating how much they ache and how they have to spend 24/7 on the couch, are, by the same token, "maximizing" the effects of tx. same equation. If sides were been minimized here, why are there so many freaked out about tx?


the fact that geno 2 and 3 only have to treat 24 wks, does not benefit the so call risk/reward ratio.  Susceptible individuals can have severe adverse effects the first two months of tx. So, stating that it makes sense to offer tx to one genotype and not the other because one only does 24 wks and thus has less chance of severe effects is misleading. I do believe it has to do with cost, the same reason they want to cut the tx in Europe. MONEY.

If length of tx is the factor that weighs on the risk factor, why is it not manifested in these extended tx studies?

"ADVERSE EVENTS

The rates of commonly reported adverse events were the similar for patients whether they received 48 or 72 weeks therapy. Serious adverse events were 5% for 48 weeks & 8% for 72 weeks. There were no previously unreported AEs.

TREATMENT DISCONTINUATION

At week 24, disct was 12% in 72 week grp & 11% in the 48 week grp, the same. At week 48, disct was 18% in the 48 week grp 7 27% in the 72 week grp. And at week 72 the disct rate was 36%."

treatment was discontinued the same for both the 48 group as the 72 group at wk 24. You can make a correlation on the 24 and 48 group with these numbers, can you?

by jmjm530, Jan 20, 2006 12:00AM
To: Cuteus and ALL
(A) JmJm said initially:"While some will disagree, my take is that MH, compared to other boards, has a pro-treatment bias in the sense that tx sides/risks are minimized in the risk/reward tx equation.."

(B)Cuteus responds: "members stating their personal experiences and those of the folks with similar experiences of mild to moderate side effects on tx, should not be considered "minimizing tx side effects". They are stating a fact as it pertains to them. If it is to be considered "minimizing", then folks stating how much they ache and how they have to spend 24/7 on the couch, are, by the same token, "maximizing" the effects of tx."
----------------------------------------------------

Wow. Can you please tell me how "B" follows "A" ???

I was clearly talking about treatment bias on the board in terms of advice/opinions/analysis, etc, and in NOT in any way inferring that people are either either "minimizing" or "maximizing" their individual treatment experiences. I value everyone's personal experience at face value and hope others do as well.

by andyarundel, Jan 20, 2006 12:00AM
I find this thread very amusing, as it seems some have the opinion that they have a magic looking glass into what works for what genotype with regard to treating HCV.Bottom line is for those individuals who are or considering treatment. The sucess rate will either be 100%, or 0%. That I can guarantee.At this day and age anything else if fluff. For a layman to sit and read abstracts on HCV treatment and thus try to attempt to re-distribute this info to us may be thrilling for a few, but really only serves the distributor. There are a few studies that may suggest this or that, but at the end of the day, each person is an individual and thus using these abstracts to try to predict success or the lack of success is a fool’s paradise.

One cannot mix anecdotal experience and then somehow magically mix this into clinical abstracts. I would suggest those considering treatment weigh the risks against the need to treat. Anything else is just noise from a person who I would suspect has way too much time on their hands.

I would strongly suggest anyone who suffers from HCV and has had a recommendation from their Doc with regard to using interferon based medications ensure that their Doc fully abridge them of the risks associated with this class of medications and not pay any attention to percentages early PCR’s and a range of other complete nonsense suggested here in this forum. I would however also suggest that if one were contemplating treatment, that one glean from the posters at MH, some of the problems associated with treatment, but with the expectation that since there is such a small cohort of patients here the chances of anyone here to cause an effect with their treatment plan are slim to nil and slim is on vacation.

I was under the impression that this was a support forum, and thus would be on the level that anyone would find it comfortable to post with any question with regard to HCV. I trust some with their arm chair clinical opinions would keep this in mind and remember to save some space for those who may wish to ask a question, or possibly give some insight without feeling that their opinion may not be welcome in such high brow forum occupied by a few elitist medical wanna be’s.  

by jmjm530, Jan 20, 2006 12:00AM
To: Cuteus and ALL
Cuteus quotes a study: "The rates of commonly reported adverse events were the similar for patients whether they received 48 or 72 weeks therapy. Serious adverse events were 5% for 48 weeks & 8% for 72 weeks. There were no previously unreported AEs.
=====================================================
Logic aside -- and logic dictates that the longer you're on these drugs NOT the better -- many of the shorter-course studies suggest the opposite of what you quote above.

One example is from the European short-course study:

"...for patients who become HCV RNA negative at week 4, treatment for 24 weeks has similar high efficacy with superior safety compared to 48 week therapy."
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