Patients with hepatitis C virus (HCV) infection who are being treated for opioid addiction with opioid-agonist therapy (such as methadone or buprenorphine) benefit from therapy with the interferon-free combination of elbasvir-grazoprevir, according to a recent industry-funded study.
Researchers performed a randomized, placebo-controlled, double-blind trial in patients from 12 countries who had chronic infection with HCV genotypes 1, 4, or 6; were treatment-naïve; had been receiving opioid-agonist therapy with methadone, buprenorphine, or buprenorphine-naloxone for at least 3 months before enrollment; and were at least 80% adherent to appointments for opioid-agonist therapy. Active use of drugs of potential abuse was not an exclusion criterion. Patients were randomly assigned to receive immediate treatment, defined as elbasvir-grazoprevir for 12 weeks, or deferred treatment, defined as placebo for 12 weeks, no treatment for 4 weeks, and open-label elbasvir-grazoprevir for 12 weeks.
The study's primary outcome, sustained virologic response at 12 weeks, was evaluated separately in the immediate and deferred groups. Secondary outcomes were sustained viral response at 24 weeks, viral recurrence or re-infection, and adverse events. Merck & Co., Inc., which manufactures elbasvir-grazoprevir, funded the study. Results were published online Aug. 9 by Annals of Internal Medicine.
Two hundred one patients were assigned to the immediate treatment group, and 100 were assigned to the deferred treatment group. Of all 301 patients, 76.4% were men and 80.1% were white. Patients received a once-daily, fixed-dose combination of elbasvir, 50 mg, and grazoprevir, 100 mg. During the first 12 weeks of the study, adherence above 95% was reported in 96.5% of the initial treatment group and 100% of patients in the deferred treatment group. In the active phase of the deferred treatment group, 95.8% of patients reported adherence of greater than 95%.
At 12 weeks, the immediate treatment group had a sustained virologic response of 91.5% (95% CI, 86.8% to 95.0%). The deferred treatment group, meanwhile, had a sustained virologic response of 89.5% (95% CI, 81.5% to 94.8%) in the active treatment period. Virologic response and adherence to HCV therapy were not affected by drug use at baseline or during treatment. Eighteen patients had post-treatment viral recurrence through 24-week follow-up, and of these, 6 had probable re-infection. One patient in each group discontinued treatment due to an adverse event (moderate-intensity abdominal pain in the immediate treatment group and development of acute respiratory distress syndrome after hospitalization for pneumonia during the placebo phase in the deferred treatment group).
The researchers noted that their findings may not be generalizable to patients who inject drugs but are not receiving opioid-agonist therapy or to patients with HCV genotype 3. They also pointed out that assessment of adherence may have promoted adherence and that data on injection drug use behaviors were not available. However, they concluded that patients with HCV infection who were receiving opioid-agonist therapy and treatment with elbasvir-grazoprevir had high rates of sustained virologic response regardless of continued drug use. “These results support the removal of drug use as a barrier to interferon-free HCV treatment for patients receiving [opioid-agonist therapy],” the authors wrote. They called for further research on the risk for re-infection.