With HIV we observered that if we use 1 drug resistance develops rapidly, with 2 drugs it is slower, and with 3 drugs it virtually never happens, so it does not come as any great surprise that combining an NS3/4A drug with an NS5A drug and and NS5B drug works well.
We have previously seen Merck retreat Zepatier failures with Zepatier+Sofosbuvir and Abbvie retreat Viekira failures with Viekira+Sofosbuvir and in both cases very good 95% SVR12 results were achieved.
We have also seen Gilead follow the same strategy by adding the NS3/4A agent Voxilaprevir to the NS5A/NS5B Velpatasvir/Sofosbuvir in Epclusa to form Vosevii.
So what happens if you take the strongest NS3/4A inhibitor ever invented – Glecaprevir, and the strongest NS5A inhibitor ever invented – Pibrentasvir, and add in the strongest NS5B inhibitor ever invented – Sofosbuvir. Could it be we have the mythical “Perfectovir”.
Abbvie have investigated this by dropping a lifeline to patients who failed G/P in their trials. Sadly they missed perfection with a 95% SVR12 (22/23) but the single patient who failed had previously failed both Harvoni and Maviret.
Anyway, for patients that have failed DAAs this is encouraging news. If we can cure 95% first time around, and then 95% of the 5% who relapsed that makes 99.75% overall and is awesome news.
The full presentation from CROI is available in the attachments to this blog post.
