Many insurance payers in the US restrict access to direct-acting antivirals (DAA) for chronic hepatitis C (HCV) infection if patients have illicit substance use or are receiving opioid agonist treatment (OAT). Three phase 3 multi-center trials (the “ION” trials) evaluated the efficacy and safety of ledipasvir/sofosbuvir ± ribavirin in patients with chronic genotype 1 HCV infection. People receiving OAT were eligible, but those with drug use in the year prior to study initiation were excluded. Illicit drug use in the period following treatment initiation did not lead to discontinuation from these trials. In this post hoc analysis, researchers evaluated the impact of OAT (among patients enrolled in all phase 3 ION trials) and illicit drug use measured by serum toxicology testing on stored samples during therapy on: HCV treatment completion (among patients enrolled in the ION 1 trial only), adherence, sustained virologic response (negative HCV RNA viral load) 12 weeks post-treatment (SVR12), and safety of ledipasvir/sofosbuvir ± ribavirin.
- Among 1952 patients enrolled in the ION trials, 4% (n = 70) were receiving OAT. Compared with those who were not, there were no significant differences in treatment completion (97% versus 98%), ≥80% medication adherence (93% versus 92%), SVR12 (94% versus 97%), or serious adverse events (4% versus 3%).
- 23% (n = 196) of patients in the ION 1 trial had toxicology testing consistent with illicit drug use during HCV therapy (15% cannabinoids alone; 8% other illicit drugs ± cannabinoids). There were no differences in treatment completion, ≥80% adherence, SVR12, or serious adverse events in those with no drug use during treatment compared with those who used cannabinoids and/or other illicit drugs.
These trials included highly select populations, included a small number of people receiving OAT, and excluded people with recent drug use at treatment initiation, so the findings may not be representative of the general population of patients with drug use. However, these data suggest that HCV treatment outcomes in patients who have drug use and/or are receiving OAT can be comparable with regard to treatment completion, medication adherence, SVR12, and safety to those of other patients treated for HCV. These data add to the growing body of literature that indicates active substance use should not be considered a contraindication to HCV treatment with DAAs.
Jeanette M. Tetrault, MD
Grebely J, Mauss S, Brown A, et al. Efficacy and safety of ledipasvir/sofosbuvir with and without ribavirin in patients with chronic HCV genotype 1 infection receiving opioid substitution therapy: analysis of phase 3 ION trials. Clin Infect Dis. 2016;63(11):1405–1411.