HALT-C study

[Trish77]

I read the following excerpt that references the HALT-C study:

Data presented by Mitch Shiffman from the HALT-C study, which Afdhal referred to in this oral talk at DDW, showed dose reductions in ribavirin had a more negative effect than a dose reduction in Pegasys on end-of-treatment response and sustained viral response in the HALT-C study. Shiffman reported that sustained viral response was 23% (n=118, no dose reductions) and when there was a dose reduction only in Pegasys the SVR was still 23% (n=70). But when only ribavirin dose was reduced (n=36) the sustained viral response (SVR) was 11% (23% vs 11%, p<0.008). When there were dose reductions for both Pegasys and ribavirin the SVR was 8%.

I want to read the study and determine in what context the above conclusions were arrived at.  If you can help me locate this study, I would be immensely grateful.  I've seen it referred to often enough, you'd think I could find the actual study but I can't as yet and... well, I've been researching to death all day and getting a little battle weary and on this one, I just thought I'd ask for help.

(To the other person I sent this same request to ..... I'm a little impatient to get the information, so ...decided to post and take the "scattergun" approach. :)

[Trish77]

I'm good fret.  I've got my ground.  Just too bloody tired to post it and I've learned so much going through all the ins and outs that I want to share it when I post it.  Rag doll at the moment though and heading to bed.

You are one of a kind and I appreciate you.

Trish

[fretboard]

Yes I agree, you should read up on this subject as much as you can.  The bottom line in all of this is, it is your decision.  I really wish someone would have responded to the other post you put up, maybe someone will catch it later.  good luck with your decision.

[Trish77]

Yes, that little excerpt raised alot of questions for me too.  That's why I wanted to read the context under which those comments were made and they may pertain only to a narrow circumstance most likely and not in general.  The two extra components that fret noted seem to bear this out.  Further reading is required.  

Nobody should take the excerpt I posted as being representative of any ribavirin reduction at all under any circumstance.  It has no context with it.  In retrospect, I should not have posted that excerpt without context for the unfounded concern it may cause to some people.  I should simply have asked for pointers to the HALT-C study materials.

Trish

[Trish77]

Didn't know there WAS a main site... or I imagine I'd have had no need to post this in the first place.  Thanks for the heads up.

fret ... thank you.  That helps alot especially right now.  Dunno why I couldn't pull up anything useful.. maybe something about 1am and out of steam and patience.  Thanks for your tolerance and for kicking in.  Appreciated.

Trish

[fretboard]

Here's another, these come only in abstract form.  Maybe after I get a little more comfortable with pubmed I will learn to get more, but I think the whole study would have to be requested from UC Berkeley.  Hope this helps.  The conclusions on this one may be little more to your liking.   later

Impact of ribavirin dose reductions in hepatitis C virus genotype 1 patients completing peginterferon alfa-2a/ribavirin treatment.Reddy KR, Shiffman ML, Morgan TR, Zeuzem S, Hadziyannis S, Hamzeh FM, Wright TL, Fried M.
University of Pennsylvania, Philadelphia, Pennsylvania, USA. rajender.***@****

BACKGROUND & AIMS: To maximize sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) infection, treatment with pegylated interferon and ribavirin has been genotype-specific (1 vs non-1). We evaluated the effects of ribavirin and peginterferon alfa-2a dose reductions on SVR in patients infected with HCV genotype 1. METHODS: Data were pooled from 569 patients enrolled in 2 phase III trials of 48 weeks of treatment with peginterferon alfa-2a and ribavirin. All patients were evaluated for the effect of cumulative drug exposure on 4- and 12-week responses, and the 427 patients who completed treatment were evaluated for effect of drug exposure on SVR. RESULTS: Of patients who completed treatment, more had reductions (< or =97% cumulative dose) of ribavirin than of peginterferon alfa-2a (43% vs 27%). Neither early virologic response nor SVR was affected adversely by ribavirin reductions when the cumulative ribavirin exposure was greater than 60%. The SVR was reduced significantly (P = .0006) in patients with less than the 60% cumulative ribavirin dose and was associated with prolonged periods of dose reduction, temporary interruptions, or premature cessation of ribavirin. Ribavirin dose reductions had minimal impact on SVR in patients who achieved rapid virologic response, defined as undetectable HCV RNA levels after 4 weeks, even when they received less than the 60% cumulative ribavirin dose. In contrast, SVR was reduced markedly in patients who had ribavirin dose reductions and did not achieve rapid virologic response. CONCLUSIONS: Minor ribavirin dose reductions to manage adverse events do not appear to affect SVR adversely, unless cumulative exposure is less than 60%. Prospective studies, however, are required to establish the impact of ribavirin dose reduction on SVR.

[foofighter]

Did you go to the main site? I suppose it is a ton of stuff to sort though:

http://www.haltctrial.org/publications.html

Hector posted this link to a video that is a great video (long) and she does put up a couple of Halt C slides with results. You might find it interesting:

http://www.uctv.tv/search-details.asp?showID=14086

Foo

[r4c7]

The information you sight from HALT-C raises a lot of questions.  For example,  I would doubt that minor or infrequent dose reductions of ribavirin would have only a negligible effect on rapid and early viral responders.  Also, ribavirin reductions late in treatment would seem to have little effect, whereas early reductions might have more pronounced effect on SVR.

Although I would think dose reductions of ribavirin should be avoided where possible, I'm not certain that minor dose reductions due to anemia or other side effects would cause a major disruption in one's outcome.  At the same time, I would think that a complete elimination of ribavirin could change a successful outcome into a relapse.  

[fretboard]

Here's the one I came across, don't know if you've already read it or not.  Good Luck

Impact of reducing peginterferon alfa-2a and ribavirin dose during retreatment in patients with chronic hepatitis C.Shiffman ML, Ghany MG, Morgan TR, Wright EC, Everson GT, Lindsay KL, Lok AS, Bonkovsky HL, Di Bisceglie AM, Lee WM, Dienstag JL, Gretch DR.
Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA. ***@****

BACKGROUND & AIMS: Reducing the dose of peginterferon and/or ribavirin to  or =98%) to  or =98%) to < or =60% did not affect either W20 VR or SVR as long as ribavirin dosing was not interrupted for more than 7 consecutive days. Prematurely discontinuing ribavirin, even at full-dose peginterferon, reduced W20 VR to < or =19% and SVR to < or =4%. CONCLUSIONS: Reducing the peginterferon dose during the first 20 weeks of treatment reduced viral clearance and SVR. In contrast, reducing ribavirin did not affect either W20 VR or SVR as long as patients remained on full-dose peginterferon. Discontinuing ribavirin prematurely was associated with a marked decline in both VR and SVR.