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

Abstract

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.

Fig 1. Flowchart describing the process of assigning patients to the directly observed therapy-group (DOT) or "standard setting" (SS).

Abbreviations: IDU, intravenous drug use; OAT, opioid agonist therapy; DAA, direct acting antivirals; SS, standard setting; DOT, directly observed therapy. Patients without a history of intravenous drug use (IDU) presenting at the tertiary care center were assigned to the SS-group. Also, patients with a history of IDU and presumed excellent compliance concerning adherence to DAA-therapy presenting at the tertiary care center or at the low-threshold facility were treated according to the SS. Patients on OAT with presumed high risk of non-adherence to DAA-therapy according to a unanimous decision between the members of the interdisciplinary evaluation team were assigned to the DOT-group. In case of different opinions among the evaluation team members concerning patients’ presumed compliance, the DOT setting was selected.

Fig 2. Cascade of care.

Abbreviations: SS, standard setting; DOT, directly observed therapy; SVR, sustained virologic response; LTFU, lost to follow-up. ^a for reasons not related to therapy.

Fig 3. SVR12 rates after treatment with SOF/VEL after LTFU exclusion.

Abbreviations: SVR, sustained virologic response; SOF/VEL, sofosbuvir/velpatasvir; LTFU, lost to follow-up; SS, standard setting; DOT, directly observed therapy; HCV, hepatitis C virus; GT, genotype. A—All patients (n = 197/221). ^a including n = 2 patients who died for reasons not related to treatment after showing a negative HCV-RNA PCR result at week 2 of therapy and at the end of treatment, respectively. B—Patients with advanced fibrosis (n = 98/109). Advanced fibrosis was defined as F3-F4: ≥9.5 kPa according to transient elastography. ^b including 1 patient who died for reasons not related to treatment after showing a negative HCV-RNA PCR result at week 2 of therapy. C—Patients with HCV GT3 infection (n = 94/100).