Biotech Values

[iwfal]

Was HCV resistant or was it hiding in relapsed T patients?

It turns out that this data was published as part of the PROVE-2 data:

Among the 22 patients who has viral breakthrough during the 12 weeks of telaprevir administration and had a viral RNA level above the limits of the sequencing assay, wild-type virus was found in 1 (5%), variants with low-level resistance in 9 (41%), and variants with high-level resistance in 12 (55%). Among the 42 patients who had a relapse after completion with telaprevir and had a viral RNA level above the limit of detection of the sequencing assay, wild-type virus was found in 2 (5%), low-level resistant variants in 33 (79%) and high-level resistant variants in 7 (17%). In some patients who did not receive ribavirin, complex changes in sequence were seen during the study.

Possible interpretations:

a) Relapse appears to require that the virus become at least low level resistant - which is likely to be a lot harder with two independent DAAs. HCV can't 'just' hide.

OR

b) HCV can hide long enough to inevitably starting to develop low level resistance.

#a would appear more likely.

Also note the interesting data about lack of ribavirin causing 'complex' changes in HCV sequence - which appears to be at odds with one of the postulated MOAs of ribavirin, which is that it boosts the mutation rate of HCV.