Long-term outcome in people who use drugs successfully treated for hepatitis C infection with glecaprevir/pibrentasvir.

Background: Several clinical trials, including the recently published the GRAND PLAN study from Vancouver Infectious Diseases Center (VIDC), have demonstrated the efficacy of hepatitis C (HCV) therapy among active drug users, including those facing significant addiction-related and social challenges. In the GRAND PLAN, we documented sustained virological response post-treatment Week12 (SVR12) in 108/117 (92.3 %) individuals (108/111 (mITT) or 97.3 % of those reaching the SVR12 timepoint) receiving an 8-week course of glecaprevir/pibrentasvir (G/P), with almost all using fentanyl and over half being unstably housed. Data on the maintenance of this favorable outcome in the long-term in such a population with a significant risk of reinfection is limited. We hypothesized that the offer of ongoing multidisciplinary care (including addiction care) after SVR12 was achieved would reduce the likelihood of loss to follow up, HCV reinfection or death and consolidate the gains achieved by initial engagement in care to diagnose and treat HCV infection.

Methods: The inception cohort for this analysis was the 108 individuals achieving a cure of HCV infection within the GRAND PLAN study. All were offered the opportunity to continue to receive care at the VIDC. This is a multidisciplinary model of care to address medical, mental health, social and addiction-related concerns on an ongoing basis. This included, if necessary, opiate agonist and safer supply therapy, usually provided by the pharmacy adjacent to our inner-city campus. Among those choosing to be retained in care, the endpoint of this analysis was loss to follow up, mortality and HCV reinfection and their correlates. Reinfection was ascertained by repeat HCV RNA testing every 6 months, more frequently if clinically indicated.

Results: Of the 108 individuals making up the inception cohort for this analysis, all chose to remain in care at the VIDC. We note a median age of 47 (22-75) years, 28 % female, 21.3 % identifying as indigenous, the majority with mild fibrosis (90.8 % F0-F2), slightly more than half with unstable housing. It is of note that we recorded a 20 % decrease in fentanyl users among those who were cured compared to the baseline evaluation of the overall study cohort (73.5 % vs 94.9 %, p < 0.000001). Among the cured individuals, 104 (96.3 %) remained alive, while 4 individuals died of opioid overdoses. Out of the 104 , 99 (95.2 %) remained HCV-free, while 5 (4.8 %) were re-infected. All five have recently initiated repeat HCV therapy at VIDC, 2 of whom are already documented to be cured.

Conclusion: Among a population of vulnerable inner-city residents cured of HCV infection within a multidisciplinary program of care at the VIDC, all individuals accepted the offer to remain in long-term follow up, with a statistically significant reduction in fentanyl use over time. In the setting of an ongoing opioid crisis where 3 deaths/day are recorded in the neighborhood where the study population resides, we documented 4 deaths. Reinfections occurred at a very modest rate, with maintenance in care allowing prompt re-treatment, with a cure already being documented in 2/5 cases, with the other 3 individuals remaining on HCV therapy at the VIDC.