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Hepatitis C Reinfection Rates Low After Successful Treatment in People Who Inject Drugs


Treatment of hepatitis C virus (HCV) with direct-acting antiviral medications was associated with low HCV reinfection rates among patients who inject drugs, although risk for reinfection was highest in the first 24 weeks of treatment and among those with ongoing injecting drug use.

Low hepatitis C virus (HCV) reinfection rates were shown in patients who inject drugs (PWID) after successful treatment with direct-acting antiviral (DAA) medications, according to study findings published today in the Annals of Internal Medicine.

Although DAA medications are considered safe and effective among PWID receiving opioid agonist therapy (OAT) and those with recent injecting drug use, risk of HCV reinfection has been noted to potentially reduce the benefits of cure among these patients and compromise HCV elimination efforts.

A recent systematic review estimated that the rate of HCV reinfection after successful DAA treatment was 6.2 per 100 person-years among people with recent injecting drug use and 3.8 per 100 person-years among those receiving OAT, noted the study authors. If left untreated, HCV infection can lead to serious hepatic complications, liver failure, and death.

“Systematic reviews, however, are limited in their ability to explore individual-level factors associated with reinfection and the capacity to investigate the natural history of HCV reinfection,” said researchers.

To address these limitations, they conducted a long-term extension analysis of the CO-STAR (Hepatitis C Patients on Opioid Substitution Therapy Antiviral Response; NCT02105688) phase 3 trial evaluating elbasvir (50 mg) and grazoprevir (100 mg) in patients with HCV infection receiving a stable OAT regimen.

In the trial, the intention-to-treat (ITT) population sustained virologic response (SVR) was 91% and the modified ITT population (excluding those who discontinued for reasons unrelated to treatment) SVR was 96%.

Eligible participants aged 18 years and older with chronic HCV infection, with genotypes 1, 4, or 6, from the CO-STAR study were evaluated on the rate of HCV reinfection for 3 years after successful treatment. An additional analysis investigated the effect of injecting drug use on the rate of HCV reinfection.

Among 296 participants who received treatment, 286 were evaluable for reinfection and 199 were enrolled in the long-term extension study. Patients were followed every 6 months for up to 3 years.

Across the 604 person-years of follow-up, 10 participants had a total of 11 HCV reinfections, or a reinfection rate of 1.7 (95% CI, 0.8 to 3.0) per 100 person-years, in which 6 of the reported reinfections occurred within 24 weeks of completing treatment. A higher rate of reinfection was observed in people with recent injecting drug use (1.9; 95% CI, 0.5 to 4.8) per 100 person-years (212 person-years of follow-up).

Ongoing drug use and injecting drug use were reported by 59% and 21% of participants, respectively, at the 6-month follow-up visit and remained stable during 3 years of follow-up.

The study authors noted that the requirement for enrolled participants in the study to be 80% adherent to OAT at baseline is a potential limitation of the findings as it may represent a population with higher stability and lower risk for HCV reinfection.

Following these findings, they said that at an individual level, an assessment of HCV reinfection risk should be done before initiating DAA therapy, and at a population level, efforts to reduce primary and reinfection incidences require the appropriate provision of health care with universal access to programs for persons with both HCV infection and injection drug use.

“Supporting retention in care will also ensure that services can be person-centric and address other drug-related harms and comorbidities among PWID,” they added. “Moving forward, enabling broad access to needle and syringe programs and OAT services in combination with HCV treatment programs will be critical among PWID.”


Grebely J, Dore GJ, Altice FL, et al. Reinfection and risk behaviors after treatment of hepatitis C virus infection in persons receiving opioid agonist therapy. Ann Intern Med. Published online August 8, 2022. doi:10.7326/M21-4119

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