I think that the subject of drug Resistance to NS3 and NS5A class drugs is an important one for anybody taking these classes of drugs, eg. simeprevir, ledipasvir, daclatasvir. I am not the expert on this subject, I can only cite my own story.
I did a trial back in 2007 using telaprevir, an NS3 protease inhibitor. I figured, what the he!!, the worst that can happen is that it doesn't work. I was wrong. What did happen was that most people in my arm of the trail failed to reach SVR, including me, and I was left with drug resistant variants to the NS3 class of drugs which limited my possibilities for treatment going forward.
***Nobody told me that this might happen.***
Back then I might have still done the trial even if somebody had explained to me about drug resistance. With hindsight and the knowledge that has been gained since then, I wouldn't have done it. The difference between now and back then is that now we have very effective drugs and the chances of getting to SVR first time around are very high. So the risk of failing and being left with drug resistance is very small. I am only writing about it here because nobody told me about it and I think that was wrong. Somebody should have told me. I didn't know that it was a risk that I was letting myself in for, and I should have been informed. So now you all are.
As an interesting aside to this - I read an article abstract recently where contrary to "response driven" management of treatment in the past - the author was raising the question whether - future treatment might become guided by assessing "resistance".
Fem. Gen 1a.18.4 kPa. IL28b - CT. Cirrhosis 4B/c. MELD 11. Portal Hypertension. Ascites. Varices. (Gr.3). post surgical Coma 2011- Tx denied. 15/09 - INR 1.2 platelets 58 (150-450) albumin 32 (35-50) bilirubin 40 (2-20) ALT 183 (0-45) AST 281(0-41) GGT 39(0-45). Liver lesions AFP 16 <8.
I relapsed after Boceprevir + Ribavirin + interferon a couple of years ago. I am G1. My problem was white & red blood cells dropping dangerously low resulted in lowering of dose. I've been worried about what resistance might have developed ever since, so I'll be closely following this topic. Here's something I just found that's rather hopeful:
"A combination of DCV and a nucleotide analogue inhibitor of HCV RNA-dependent RNA polymerase, sofosbuvir, with or without ribavirin for 24 wk achieved SVR in 100% of untreated HCV genotype 1a and 1b patients (n = 44) as well as in HCV genotype 1a and 1b patients (n = 41) who failed to respond to prior treatment with telaprevir or boceprevir, peginterferon and ribavirin. SVR was achieved in 93% of patients infected with HCV genotypes 2 and 3 (n = 44)[89,90]."
41 patients who failed telaprevir and boceprevir must surely have included people with resistant varieties. Interesting that the excellent result was achieved both with and without Ribavirin.