CHIME - A tailored HCV microelimination project in Viennese people who inject drugs at drug centralized substitution centers.

Background: Hepatitis C remains highly prevalent among people who inject drugs (PWIDs). We propose an integrated approach for screening/diagnostic testing and treatment in 6,665 Viennese PWIDs registered to access opioid agonist therapy (OAT). Methods: OAT prescriptions were required monthly at one of nine approved authorities, making them ideal platforms for hepatitis C virus (HCV) screening. All PWIDs attending these authorities between January 2019 and March 2020 were offered on-site HCV screening, and consecutive HCV RNA PCR in case of positive HCV serology. In HCV viremic PWIDs, offsite referral to HCV care and treatment according to directly observed therapy (DOT) alongside OAT were performed. Results: 4,327/6,665 (64.9%) individuals were contacted before the COVID-19-related project discontinuation. There were 1,538/4,327 (35.5%) individuals who had participated in the study. HCV serology was available in 1,510/1,538 (98.2%): 795/1,519 (52.6%) had a positive serology, among whom 632 (79.5%) were followed-up with a PCR test. In 8/1,538 (0.5%) additional study participants HCV RNA PCR was assessed without prior serological screening. 239/640 (37.3%) individuals were HCV viremic with 51 (21.3%) having started on direct-acting antivirals (DAAs). 48/51 (94.1%) had completed treatment, among whom 42 (87.5% according to ITT) had achieved sustained virologic response at 12 weeks after completing treatment (SVR12) and 6 (12.5%) had been lost to follow-up after completion of therapy (SVR12 according to mITT: 42/42, 100%). No treatment failures had occurred. Conclusion: Providing integrated point-of-care HCV screening/diagnostic testing at central OAT approved centers, followed by DOT with DAAs, represents an effective HCV microelimination strategy. While some PWIDs were lost in the cascade to cure and the absolute number of SVR was limited by the COVID-19 pandemic, our approach will allow linkage to care in a large proportion of Viennese PWIDs.

Directly observed therapy at opioid substitution facilities using sofosbuvir/velpatasvir results in excellent SVR12 rates in PWIDs at high risk for non-adherence to DAA therapy.

BACKGROUND & AIMS: We evaluated the effectiveness of sofosbuvir/velpatasvir (SOF/VEL) in difficult-to-treat PWIDs with presumed high risk for non-adherence to antiviral therapy using an innovative concept involving their opioid agonist therapy (OAT) facility. METHODS: N = 221 patients (m/f: 168/53; median age: 44.7 years (IQR 16.9); HCV-genotype 3: 45.2%; cirrhosis: 33.9%) treated with SOF/VEL were included. PWIDs at high risk for non-adherence to DAA therapy (n = 122) received HCV treatment alongside OAT under the supervision of medical staff ("directly observed therapy", DOT). These patients were compared to patients with presumed excellent drug compliance, who were treated in a "standard setting" (SS) of SOF/VEL prescription at a tertiary care center (n = 99). RESULTS: DOT-patients (n = 122/221; 55.2%) were younger than SS-patients (median age: 41.3 vs. 53.0 years), all had psychiatric comorbidities and most had a poor socioeconomic status. 83/122 (68.0%) reported ongoing intravenous drug use. Within the DOT-group, SVR12 was achieved in 99.1% (95% CI: 95.0-100; n = 109/110) with one patient experiencing treatment failure, while n = 12/122 (9.8%) patients were excluded due to loss of follow-up (FU). 5 patients showed HCV reinfection after achieving SVR12. SS-patients achieved SVR in 96.6% (95% CI: 90.3-99.3%; n = 84/87) after exclusion of 10/99 (10.1%) patients who were lost to FU and 2 patients who died prior to SVR12 due to reasons not related to DAA therapy. CONCLUSIONS: SOF/VEL given as DOT along with OAT in PWIDs at high risk of non-adherence to antiviral therapy including those with ongoing intravenous drug use resulted in excellent SVR rates similar to patients with presumed "excellent compliance" under standard drug intake.

Directly observed therapy for HCV with glecaprevir/pibrentasvir alongside opioid substitution in people who inject drugs-First real world data from Austria.

BACKGROUND: Directly acting antivirals (DAA) against hepatitis C virus (HCV) infection have facilitated sustained virologic response (SVR) rates >90% in clinical studies. Yet, real life data regarding DAA treatment in people who inject drugs (PWIDs) are scarce. We evaluated the effectiveness of glecaprevir/pibrentasvir (G/P) in difficult-to-treat PWIDs with presumed high risk of non-adherence to DAA therapy using the concept of directly observed therapy involving their opioid substitution therapy (OST) facility. METHODS: N = 145 patients (m/f: 91/54; median age: 41.1 (IQR 19.5) years; HCV-genotype (GT) 1/2/3/4: 82/1/56/5, GT3: 38.6%; cirrhosis: n = 6; 4.1%) treated with G/P were included. PWIDs at high risk for non-adherence to DAA therapy received HCV treatment together with their OST under the supervision of medical staff ("directly observed therapy", DOT). The effectiveness of G/P given as DOT in PWIDs with presumed high risk of non-adherence to DAA therapy was compared to patients with suspected "excellent compliance" in the "standard setting" (SS) of G/P prescription at a tertiary care center and self-managed G/P intake at home. Treatment duration was 8-16 weeks according to the G/P drug label. RESULTS: DOT-patients (n = 74/145; 51.0%) were younger than SS-patients (median 38.7, IQR 12.5 vs. median 50.6, IQR 20.3 years), all had psychiatric co-morbidities and most had a poor socioeconomic status. 50/74 (67.6%) reported ongoing intravenous drug use (IDU). SVR was achieved in n = 70/74 (94.6%) patients with n = 3 being lost to follow-up (FU) and n = 1 showing nonresponse to therapy. SS-patients achieved SVR in 97.2% (69/71) with n = 1 patient being lost to FU and n = 1 patient with GT3 showing HCV relapse. CONCLUSION: G/P given as DOT along with OST in PWIDs with high risk of non-adherence to DAA therapy resulted in similarly high SVR rates (94.6%) as in patients with presumed "excellent compliance" under standard drug intake.

Efficacy of ledipasvir/sofosbuvir plus ribavirin for 12 weeks in patients with chronic hepatitis C genotype 3 and compensated liver disease.

INTRODUCTION: In the era of direct-acting antivirals, hepatitis C virus (HCV) genotype (GT) 3 remains as the most difficult-to-treat HCV-GT. Currently, data on the efficacy of ledipasvir/sofosbuvir plus ribavirin (SOF/LDV+RBV) in GT3-infected patients are limited. We investigated the efficacy of this regimen in a real-life cohort from Austria. PATIENTS AND METHODS: A total of 55 patients with HCV-GT3 and compensated liver disease (20% treatment-experienced, 33% with cirrhosis, 7% with HIV coinfection) from four Austrian hepatitis centers received treatment with SOF/LDV+RBV for 12 weeks. The primary endpoint was sustained virological response 12 weeks after end of therapy (SVR12). RESULTS: In the modified intention-to-treat analysis - excluding patients lost to follow-up - the overall SVR12 rate was 94% (95% confidence interval: 84-99%). In treatment-naive and treatment-experienced patients, SVR12 rates were 95 and 89%, respectively. SVR12 rate was 91% in patients without cirrhosis and 100% in patients with cirrhosis. There were no serious adverse events. Viral sequencing did not show the presence of any resistance-associated substitutions in any of the three relapsed patients. CONCLUSION: Despite a very weak antiviral activity of ledipasvir against HCV-GT3 in vitro, a 12-week course of SOF/LDV+RBV was highly effective, with a 94% SVR12 rate in our cohort of compensated HCV-GT3-infected patients. Thus, if pangenotypic NS5A inhibitors are not available or not reimbursed by insurances, SOF/LDV+RBV seems to be an effective alternative in patients with HCV-GT3 infection.