I've been trying to get my head around these results. Not there yet, but here are some initial thoughts. Please correct me if I'm wrong on any of this.
First: to my mind, this trial is totally different than the HCV trial. The HCV trial was a measure of efficacy, this is much more a proof of concept. The numbers aren't as important here as achieving the threshold finding that BIT225 has some effect.
How come? The HCV trial was measuring the amount of hep c virus in the blood, so it was very easy to conduct: simply take a blood sample every few days and measure the amount of virus. This HIV trial is much more complicated: it's trying to to get some indication if BIT225 prevents/reduces HIV replication from macrophage cells buried deep within the tissue of infected people. Now digging around in the tissue of HIV-infected, treatment-naive patients is highly invasive and rather problematic, so this trial uses a fair bit of lateral thinking. As I understand it, it takes the CD14+ cells from the bloodstream before they enter the tissue, puts them in a petrie dish surrounded by T cells, and sees if the virus spreads.
Important to note here that CD14+ cells only hang about in the bloodstream for about a day before embedding themselves into tissue (where they can reside for another six weeks) so all the cells have had about one days exposure; the cells extracted on day 10 of this trial haven't had 5 days more exposure to BIT225 than those extracted on day 5. So it may not be surprising that there isn't any great difference between the 5 day bleed and the 20 day bleed.
Now it seems that there is fairly rapid replication of the virus up until day 5 in the petrie dish, and then it tapers off in both the placebo and in the BIT225 treated cultures. This could be because most of the virus that is going to spread has spread.
So perhaps the most important data is the status at 3 and 5 days in culture, where the viral replication is clearly slower amongst cells treated by BIT225 than in the placebo. It's possible the effect is clearer in the high viral load samples simply because more of the statistical noise of such an imprecise trial method is overcome. (we're talking pica-grams per nano-litres here)
Then, after the five day mark, the important thing is not to see whether the amount of virus falls; remember, the virus is now in the T-cells and BIT225 does not target T-cells. However, if the level of virus plateaus for the next 5 or 10 days, then that suggests the effects of bit225 are more or less permanent.
So what does all this mean? Bit225 is designed to impede viral replication in CD14+ cells, which can live for up to six weeks in the tissue of HIV-infected people. But by definition, all the cells plonked in the petrie dish in this trial were approximately a day old, some a lot less, so it wouldn't be surprising if some were yet to have been exposed/affected by bit225. So any statistically-measurable effect at all has got to be promising. What is happening to the macrophage cells embedded in the tissues and copping a full 10 days plus of dosing is anybody's guess.
As far as I can see, the only way to really test the efficacy of bit225 against macrophage cells embedded in the body's tissues is to dose HIV-positive patients for three months in concert with standard retro-viral treatment and then have them come off all treatment and see how quickly the virus rebounds.
What I don't know is whether the results released today are enough to attract a big pharma partner. Anybody want to hazard a guess?
BIT Price at posting:
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