Directly observed therapy of chronic hepatitis C with ledipasvir/sofosbuvir in people who inject drugs at risk of nonadherence to direct-acting antivirals.

An important subgroup of people who inject drugs (PWID) receiving opioid agonist therapy (OAT) cannot be treated in the setting of a hepatology centre and would not regularly ingest their medication when handed to them for self-administration. Our hypothesis was that chronic hepatitis C in these patients could be ideally managed if modern, interferon-free regimens were administered together with OAT under direct observation of a physician or nurse at a low-threshold facility. In this open-label, noninterventional, proof-of-concept study (ClinicalTrials.gov number, NCT02638233), 40 PWID at risk of nonadherence to direct-acting antivirals (DAA) and previously untreated chronic hepatitis C virus genotype 1 infection without cirrhosis were treated with ledipasvir/sofosbuvir for 8 weeks. Patients received antiviral treatment together with OAT under direct observation of a physician or nurse at a low-threshold facility. By following the concept of directly observed therapy, excellent adherence to antiviral therapy was achieved as follows: only 0.16% (95% CI: 0.03-0.47) of scheduled dates for ingestion of the antiviral therapy in combination with OAT were missed by the 40 patients. The rate of sustained virological response 12 weeks after end of therapy was 100% (95% CI: 91.2-100.0). Between week 12 and week 24 of follow-up reinfections were recorded in 2 of 40 patients (5%). Directly observed therapy of chronic hepatitis C is highly effective in PWID at risk of nonadherence to DAA. By this new concept, a group of difficult-to-treat patients can be cured, who could not have been treated in settings of studies published so far.