Have viruses with stable, non-reverting mutations somehow compensated for their presence and should we treat these patients and their isolates differently?
Moderator: OK, let’s move on quickly here, because we’re going to run out of some time. Let’s see, Bob and David? This is one back to you guys. [Vincent] Calvez showed that there was a significantly greater failure rate in patients who did not revert back to wild type off drug therapy. Have the viruses with stable, non-reverting mutations somehow compensated for their presence and should we treat these patients and their isolates differently?
David Katzenstein: I would say that demonstration is exactly the in-vivo fitness argument which we’ve just been discussing with regard to the last question. That yes, clearly, patients who maintain resistance mutations off drug, their virus has adapted and become at least fit enough to continue to replicate efficiently and that’s where again, the clinical question of ‘so what’s their CD4 and virus load doing?’. How do we regard patients in that position becomes the primary clinical decision maker about new drugs vs. continuing different drug pressure.
Moderator: OK, and Bob, what do you think?
Bob Shafer: Well, I agree with Dave. I’m not, I remember this but I don’t remember if this is an abstract or a paper, and I’m not really familiar with the details…what Dave says makes sense.
David Katzenstein: It’s an abstract, actually.
Bob Shafer: OK, so it’s not something that I really had a chance to digest and examine closely. I mean, I think it’s an interesting hypothesis, and it makes sense, but I really, I guess because it’s just an abstract and I hadn't had a chance to really look at it in detail, I don’t have much more to say about it.
David Katzenstein: My understanding, and I’m in the same situation as Bob with that, with regard to details, is that his findings are very similar to Veronica’s presented on numerous occasions. That in fact there is a very rapid increase in virus load and decrease in CD4 occurring more prominently in patients who "revert to wild type". Than in those who continue to manifest resistance.
Man: That’s correct. You’re exactly right, David. And the argument…
Man: I think that’s the in-vivo principle we’ve been talking about for some time now. In-vitro principle, in-vivo.
