I have now had a chance to look in detail at the poster data. I would like to add first that the following is my opinion based on my professional experience (20 years in biotech, Ph.D, etc). While I am as objective as possible, this commentary should be read as an opinion and not as some sort of gospel.
Overview
The results in general were as expected snd showed data on sCD163 level and activated T-cells changes. The surprise was the inclusion of the plasma (blood) HIV levels as we were previously told that the viral blood levels were undetectable in both treatment arms. We also got more details on the study participants and the side effects seen in each of the BIT225 and Atripla-only treatment groups (what BIT are calling the "placebo"). Looking at each area in detail we can get an idea of what BIT found and if the results are important.
Study Participants
The poster states that there was no significant difference between the two groups, however, no error bars were provided making this claim impossible to check (Table 1). Interestingly, the BIT225 treatment arm group has almost double the viral load and 16% less CD4+ cells than the placebo arm group (455 cells/mm3 verses 541 cells/mm3). The lack of statistical significance is likely due to the small size of the study as it is hard to show any significant difference when you only have 9 patients in the placebo arm.
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Side Effects
Side effects are very important for antiretroviral treatments as the patients are typically on these drugs for long periods of time. Even minor side effects can make it difficult to get patients to take their medication.
Similar to previous studies of BIT225 done at higher doses, headache was a common side effect (50% verses 22%). Pyrexia (fever) was only seen in the BIT225 treatment arm (Table 2). Various rashes were also seen in the treatment arm at a higher frequency than the placebo arm. While the side effects were not life threatening, the pyrexia in the treatment group is of concern especially given the well known effect of fever on the immune system.
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sCD163
The results of BIT225 on sCD163 were just statically significant (P = 0.036). Looking at Figure 1 the error bars (the I-shapes on the graph) were only non-overlapping at 3 of the 12 time points measured and very close to overlapping on two of these three points. The large size of the error bars indicate a wide variation between individuals, or issues with the assay. These results are weak evidence of a BIT225 effect on sCD163 at best, and could have occurred by chance alone.
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Activated CD8+ Cells
Once again large variations are seen within each treatment group for CD8+ activation with the error bars overlapping at each time point other than the second (Figure 2). BIT claims the difference between the treatment arms is statistically significant, however, no actual p-value is provided(just less than 0.05). It appears unlikely looking at Figure 2 that these results were anything other than marginally significant.
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Activated CD4+ Cells
The result shown for activated CD4+ cells display even more variation within each group than the CD8+ cell data and the error bars are non-overlapping at only 3 of 12 time points. Interestingly, the final time point measurement showed no difference between the two treatment groups.
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Virological Outcomes
This was an unexpected result as we had been told that the level of HIV in the blood was unmeasurable in both treatment groups. This was also the primary aim of the study (along with safety). Figure 4 shows that that not only was the virus level measurable, but that there was no statistically significant difference between the two treatment groups. Despite this the virus level was suppressed more in 8 of 12 measured time points in the placebo arm. The suppression was in actual viral counts was even greater in the placebo group, as the placebo arm started out with nearly twice the viral load (i.e. the graph shows the two groups normalised to 0.0 at the start of the study).
This result suggests that not only does BIT225 not help reduce the viral load in patients at the 200mg/day level, but it may actively interfere with the action of Atripla. This is an extremely concerning outcome.
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Conclusion (warning opinion)
The data does not support with any strength any of the claims made by BIT for BIT225. Most worrying is the effect of BIT225 on viral suppression where it appears to interfere with the activity of Atripla. It is my opinion that BIT will find it very difficult to get pharmaceutical industry interest to fund a phase 3 trial on the basis of the data presented in this poster. Up until now I have maintained a none sentiment, but after seeing the actual data I have taken the rare step of changing my HC sentiment on BIT to sell.
(20min delay)