All's post is worth reading a second time. Very good analysis.
I found the same. The reports are not comparing apples to apples.
And people don't understand that protease sparing does not mean protease eliminating and there are a lot of misconceptions.
Sustiva results are preliminary, not blinded, short term and not very impressive if you analyze the data reported the way it should be examined.
The Sustiva data is "Intent to treat" data, where they only look at the patients who are left in the study. The number of patients who started in the trial does not count.
They are not using a more rigorous analysis of reporting, where a non-completer=failure, which is how Agouron and others report data.
Dupont 005 study, with Sustiva 600mg +AZT+3TC, will be the basis of part of Dupont's NDA.
11/11 patients were undetectable at 36 weeks or 100% <400 copies
9/11 patients were undetectable at 36 weeks or 82% at <50 copies
Sounds good but....34 patients started in this arm and using a more rigorous method, where non-completers=failure:
11/34 patients were undetectable at 36 weeks or 32%<400 copies/ml
9/34 were undetectable at 36 weeks or 26%<50 copies/ml
Not too impressive.
So 23 patients were non-completers or 67% withdrew or were removed for viral failure, adverse effects, non-adherence and who knows??
Not too impressive.
In a study reported yesterday, comparing Viracept BID vs TID;
The most rigorous analysis was used.
BTW; 48 week data show that Viracept BID is as effective as TID
In the analysis of TID vs BID, there were 76 on TID; 212 on BID
2% withdrew out of 288 vs 67% in the Sustiva study.
80% were <400 copies at 48 weeks on Viracept +3TC+d4T
60% were <50 copies at 48 weeks """"
CD4 counts were 189 in the BID and 166 in the TID
So, which is better: Viracept (plus 2 nukes) twice a day, where 80% of patients were <400 at 48 weeks
Or should patients take Sustiva (plus 2 nukes)once a day for convenience where 32% of patients were <400 at 36 weeks??
There were more side effects and more withdrawals in the Sustiva combination than Viracept.
healthcg.com
In a different study, Sustiva and Viracept showed potent activity in treatment experienced patients: 81%<400 copies at 16 weeks, probably reflecting the prior treatment.
Protease sparing does not mean protease eliminating. No one is talking about eliminating protease inhibitors except the uninformed. Protease sparing means saving protease inhibitors for treatment after this regimen. There are a lot of misconceptions being spread. One of the assumptions underlying the use of nevirapine-containing regimens when initiating therapy, in order to "spare" protease inhibitor therapy, is the belief that nevirapine/NRTI therapy will not diminish the antiviral activity of subsequent protease inhibitor-containing therapy.>>
The big question is: Does using a protease sparing regimen lower the chances of future success using a regimen including a protease inhibitor?
We don't know yet, they say.
We do know that patients previously treated with nukes do not do as well as "na‹ve" patients on combination therapy including a protease inhibitor.
We do know that the "ole" treatment with only nukes led to CD4 increases of 40 copies/ml (Pantaleo et al).
What about the immune system? If CD4 cell counts are any indication, it doesn't look too good for Sustiva +3TC+AZT.
Today's release of 36 week for study 105 data reported CD4 increases of 100 copies/ml;
At 16 weeks the CD4 was 120 copies/ml,
At 24 weeks the CD4 was 110 copies/ml
At 36 weeks the CD4 was 110 copies/ml
Nukes and non-nukes produce resistance very quickly, especially if viral suppression is incomplete. Failing one nnrti usually means they will be cross resistance to all nnrtis.
So maybe they are sparing the Protease inhibitors, but they are reducing the choices if they are eliminating the number of nnrti's and nrti's to choose from.
Including a protease inhibitor in a regimen helps prevent resistance to nnrti's from developing.
healthcg.com
Joe Enron recommends some caution is indicated, as the study is not blinded, and durability is short, and resistance is more common on nrtis and nnrti's.
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