Glecaprevir/pibrentasvir in patients with chronic HCV and recent drug use: An integrated analysis of 7 phase III studies

Drug Alcohol Depend. 2019 Jan 1;194:487-494. doi: 10.1016/j.drugalcdep.2018.11.007. Epub 2018 Nov 24.

Abstract

Background: Injection drug use is the primary mode of transmission for hepatitis C virus (HCV), and treatment guidelines recommend treating HCV-infected people who use drugs; however, concerns about adherence, effectiveness, and reinfection have impeded treatment uptake.

Methods: Data were pooled from seven phase III trials that evaluated the efficacy and safety of 8 or 12 weeks of glecaprevir/pibrentasvir (G/P) in patients chronically infected with HCV genotypes 1-6. Patients had compensated liver disease, with or without cirrhosis, and were HCV treatment-naïve or -experienced with interferon or pegylated interferon ± ribavirin, or sofosbuvir plus ribavirin ± pegylated interferon. Patients were grouped into recent drug users (injection drug use ≤12 months before screening, positive urine drug screen [UDS], and/or drug-related adverse event), former drug users (>12 months before screening and negative UDS), or non-drug users. Assessments included sustained virologic response at 12 weeks posttreatment (SVR12), treatment adherence, and safety.

Results: Among 1819 patients, 5%, 34%, and 61% were recent, former, and non-drug users, respectively. Treatment adherence and completion were high (≥96%) regardless of drug use status. SVR12 was achieved by 93% (n/N = 91/98), 97% (n/N = 591/610), and >99% (n/N = 1106/1111) of recent, former, and non-drug users, respectively (intention-to-treat analysis). The overall rates of virologic failure were ≤1.5% across all three subpopulations, with no HCV reinfections among recent drug users. Drug-related serious adverse events and adverse events leading to treatment discontinuation were experienced by ≤1% of patients.

Conclusions: G/P is a well-tolerated and efficacious pangenotypic regimen for chronic HCV-infected people with recent or active drug use.

Trial registration: ClinicalTrials.gov NCT02604017 NCT02640482 NCT02640157 NCT02636595 NCT02642432 NCT02738138 NCT02651194.

Keywords: ABT-493; ABT-530; Hepatitis C; Injection drug use; Opioid substitution therapy.

Publication types

  • Clinical Trial, Phase III
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / therapeutic use*
  • Benzimidazoles / therapeutic use*
  • Drug Therapy, Combination
  • Drug Users*
  • Female
  • Hepacivirus
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Liver Cirrhosis / etiology
  • Male
  • Middle Aged
  • Pyrrolidines / therapeutic use
  • Quinoxalines / therapeutic use*
  • Ribavirin / therapeutic use
  • Sofosbuvir / therapeutic use
  • Sulfonamides / therapeutic use*
  • Sustained Virologic Response
  • Treatment Outcome
  • Young Adult

Substances

  • Antiviral Agents
  • Benzimidazoles
  • Pyrrolidines
  • Quinoxalines
  • Sulfonamides
  • pibrentasvir
  • Ribavirin
  • benzimidazole
  • glecaprevir
  • pyrrolidine
  • Sofosbuvir

Associated data

  • ClinicalTrials.gov/NCT02604017
  • ClinicalTrials.gov/NCT02640482
  • ClinicalTrials.gov/NCT02640157
  • ClinicalTrials.gov/NCT02636595
  • ClinicalTrials.gov/NCT02642432
  • ClinicalTrials.gov/NCT02738138
  • ClinicalTrials.gov/NCT02651194