HCV Viral Load Greater Than 1000 IU/ml at Time of Virologic Failure in Direct-Acting Antiviral-Treated Patients

Abstract

Introduction: One of the remaining barriers to reaching WHO elimination targets of achieving global hepatitis C (HCV) cure is a lack of an established lower limit of detection (LLOD) to confirm cure post-treatment in near-patient technologies. Determining a LLOD at virologic failure aids in increasing testing feasibility through point-of-care assays in resource-limited settings.

Methods: We described the level of viremia in 69 patients experiencing virologic failure across 20 clinical trials (ENDURANCE-1, ENDURANCE-2, ENDURANCE-3, ENDURANCE-4, ENDURANCE 5-6, MAGELLAN-1, MAGELLAN-2, EXPEDITION-1, EXPEDITION-2, EXPEDITION-3, EXPEDITION-4, EXPEDITION-5, EXPEDITION-8, SURVEYOR-1, SURVEYOR-2, VOYAGE-1, VOYAGE-2, CERTAIN-1, CERTAIN-2 and APRI). These findings were categorized as on-treatment, post-treatment week (PTW) 4 or PTW12 failures.

Results: The mean HCV RNA level at baseline in the overall population of 5033 patients was 4,193,712 IU/ml ± 5,955,028 (6.2 log₁₀ IU/ml ± 0.8) compared to 9,585,957 IU/ml ± 8,247,669 (6.8 log₁₀ IU/ml ± 0.5) in 69 patients experiencing virologic failure by PTW12. The mean HCV RNA level at the time of virologic failure for all patients was 6,004,980 IU/ml ± 7,077,728 (6.4 log₁₀ IU/ml ± 0.7). Twenty patients had on-treatment virologic failure with a mean HCV RNA level at the time of failure of 9,136,360 IU/ml ± 8,572,113 (6.7 log₁₀ IU/ml ± 0.7), 36 patients had relapsed by PTW4 with a mean HCV RNA level at the time of relapse of 4,131,344 IU/ml ± 5,246,954 (6.3 log₁₀ IU/ml ± 0.6), and 13 patients, who experienced relapse between PTW4 and PTW12, had a mean HCV RNA at relapse of 6,376,003 IU/ml ± 7,758,968 (6.3 log₁₀ IU/ml ± 1.0).

Conclusions: At PTW12, 100% of virologic failures had an HCV RNA > 3.0 log₁₀ IU/ml. The data are encouraging that with a LLOD of 3.0 log₁₀ IU/ml, a point-of-care test could identify all treatment failures accurately; larger studies, including real-world data, are needed to confirm these findings.

Keywords: Direct-acting antivirals; HCV RNA; Hepatitis C virus; Virologic failure.