Treating HCV in Addiction Patients Receiving Opioid Substitution Therapy
JANUARY 10, 2019
Kenneth Bender, PharmD, MA
Jason Grebely, PhDDirect acting antiviral (DAA) treatment of hepatitis C virus (HCV) produced successful long-term outcomes with rare instances of re-infection in participants receiving opioid substitution therapy (OST) for drug addiction, according to findings from a set of recent studies.
Jason Grebely, PhD, of the Kirby Institute, University of New South Wales, Australia, described the Co-STAR part B study, a three-year observational extension of the 12-week Co-STAR part A phase 3 trial of elbasvir/grazoprevir (EBR/GZR; Zepatier) in participants with HCV who were also receiving OST.
The 12-week trial in 296 participants had produced sustained virologic response (SVR12) in 91.5% of those in the immediate treatment group, and in 89.5% in the active phase of a deferred treatment regimen. There was viral recurrence in 18 of the 296 participants within that trial's 24-week follow-up, with 6 attributed to reinfection.
In the extended observation study, with 199 participants of the original cohort of 296 enrolled, HCV RNA was monitored every 6 months for 3 years. The percentage of those with positive urine drug screens was comparable to the part A trial, ranging from 42% to 54% at the monitoring visits.
"In part B, reported drug use, including injecting drug use remained stable, and sharing of injecting equipment occurred at a low frequency," Grebely reported.
A total of 10 participants had 11 cases of viral recurrence during the three-year follow-up, including the 6 participants with viral recurrence in the part A trial; with 1 observed to have a second reinfection at 30 months.
"HCV reinfection among patients on opioid agonist therapy is uncommon, despite ongoing drug use," Grebely indicated. "Data from this trial support treatment of patients on opioid agonist therapy to limit HCV infection."
Stefan Christensen, MD, Cells-in-Motion Cluster of Excellence (CIM), Praxis, Münster, Germany, presented real-world data from the German Hepatitis C Registry (DHC-R) on SVR after 12 weeks of treatment and at 24-week follow-up for 102 patients who were receiving OST, 236 patients who were former or current drug users but not on OST, and a control comparison group of 842 patients with HCV but no history of drug use.
SVR was attained at 12 weeks and maintained at 24 weeks by 95.1% of the OST group, 97.5% of those not on OST, and 98.1% of those with no drug use.
"High SVR rates could be achieved in both OST and non-OST patients," Christensen reported. "OST patients have a decreased quality of life but all patient groups benefit form HCV therapy."
Christiana Graf, MD, Department of Medicine, University Hospital Frankfurt, Frankfurt, Germany provided an overview of the data on DAA treatment of HCV concurrent with OST from her group's systematic review and meta-analysis. She pointed out that HCV is disproportionately high in people who inject drugs (PWID) and those on OST, who are at increased risk of liver-related morbidity and mortality.
"Although current guidelines recommend to consider all PWID and OST patients as candidates for DAA therapy, many physicians remain reluctant to treat these patients, citing concerns over adherence, increased susceptibility to side effects, and the risk of reinfection," Graf indicated.
Their review and meta-analysis of 11 primary articles and 12 conference abstracts comprised 1,702 patients on OST, 538 PWID and 19,723 serving as controls. There were no statistically significant difference in pooled SVR rates between PWID and controls (88% vs 92%) or between those on OST and controls (90% vs 93%).
In post-treatment outcomes, the investigators found no significant difference between groups in treatment discontinuation rates. In 10 studies which examined reinfection post-SVR, 10 of 802 patients on OST (1.25%) and 1 of 188 PWID (0.05%) experienced reinfection.
"HCV treatment outcomes in PWID and patients on OST are similar to those in the general HCV population," Graf related. "Active injection drug use and OST should not be used as a reason to withhold reimbursement of HCV therapy."
The studies were presented as posters 52, 661 and 640, respectively, at the 2018American Association for the Study of Liver Disease (The Liver Meeting).