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

Abstract

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.

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

“…Pretreatment evaluation of the study population included a detailed medical history, physical examination, abdominal sonography, standard laboratory testing, serum HCV-RNA quantification, HCV genotype (GT) assessment and determination of liver fibrosis stage by transient elastography and was performed at Klinik Ottakring or at the Ambulatorium Suchthilfe Wien. The applied methods were described in detail in a previous publication of our group [ 15 , 47 ]. The socioeconomic status was characterized by recording relationship status, housing status, employment status, criminal record and alcohol consumption habits.…”

“…Numerous phase III studies investigating the effectiveness of pangenotypic DAA have been performed recently [ 22 ]. PWIDs–and especially those with ongoing injection drug use (IDU)—were mostly excluded from these studies, however, this subpopulation represents one of the most important risk groups for HCV infection and transmission, especially because they are often unaware of their HCV-infection [ 14 , 15 , 17 , 41 – 43 ]. Psychiatric comorbidities and unstable socioeconomic circumstances are common in PWIDs—especially those with ongoing IDU.…”

“…Hence, linkage to HCV care and ensuring therapy adherence pose pivotal challenges in this patient collective and high-prevalence group. A tailored treatment approach is necessary in order to include PWIDs in international HCV elimination plans [ 15 , 42 – 45 ]. Thus, we assessed the effectiveness of an innovative concept of directly observed therapy (DOT) in PWIDs with presumed poor adherence and drug compliance, i.e.…”

Adherence to Direct-Acting Antiviral Therapy in People Actively Using Drugs and Alcohol: The INCLUD Study

“…Ingestible sensor systems in persons with HCV demonstrated mean adherence rates of 93%–97% [ 29 , 30 ], but large-scale overencapsulation of medication tablets may be challenging to implement. Modified DOT strategies comprising in-person DOT during OAT clinic visits and either self-administered tablets [ 31 ] or electronic monitoring [ 15 , 32 ] outside of clinic have been detailed, with mean adherence rates of 86%–95%. In-person DOT may be burdensome to coordinate outside of OAT clinic settings.…”

Direct patient-physician communication via a hepatitis C hotline facilitates treatment initiation in patients with poor adherence

“…general practitioners or HIV treatment centers) or peer education through patients under HCV treatment could be useful to address this population with suboptimal adherence. Strategies, such as directly observed DAA therapy alongside opioid substitution therapy in HCV patients with poor compliance have already been demonstrated to be effective in increasing adherence to and outcome of antiviral treatment in this patient population [ 27 , 28 ].…”