Challenges and Controversies

Although not rigorously studied, lapses in adherence did occur in both registrational trials as well as in some phase IV and 'real world' studies. Mostly when examined for correlation with treatment failure, even relatively long lapses of adherence don't necessarily correlate with treatment failure. Specifically, the SIMPLIFY trial of SOF/VEL x 12 weeks in a population of N = 103 PWID found that even with erratic adherence or relatively long lapses of 7-10 days, overall SVR12 was roughly 94%. Likewise in the ANCHOR trial, also in a high-risk PWID population, many took 4 months to complete 3 months worth of therapy, and still had high SVR12, approximately 90% in per protocol analysis.
This coupled with relatively long liver half-life of Glecaprevir-Pibrentasvir (6 and 12 hours T1/2 in plasma but nearly 100% liver metabolism with biliary/fecal excretion suggesting relatively high liver concentrations), and high barrier to resistance and achievement of SVR12, even if known RAMS are present suggests that pushing ahead towards completion of originally intended therapy of 8 weeks may still yield high SVR12 results.

He took 28 days of therapy and has now been off for 14 days. An HCV RNA was done that showed a level of 25IU/mL, which is the cutoff point for a negative test, so I would consider this a negative HCV RNA result. Since he has been off for 2 weeks and still has a negative HCV RNA, with genotype 1a HCV and minimal fibrosis, I would restart medication and have him finish out the planned 8 week treatment regimen.

If his viral load was >25 IU/mL, or he had HCV genotype 3, or had cirrhosis, or if I did not have repeat HCV RNA results, then I would treat him for another 8 weeks rather than 4 weeks.