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 log 10 IU/ml ± 0.8) compared to 9,585,957 IU/ml ± 8,247,669 (6.8 log 10 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 log 10 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 log 10 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 log 10 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 log 10 IU/ml ± 1.0). Conclusions At PTW12, 100% of virologic failures had an HCV RNA > 3.0 log 10 IU/ml. The data are encouraging that with a LLOD of 3.0 log 10 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.

Rapid detection of hepatitis C virus using recombinase polymerase amplification

“…The US genotype distribution is approximately 75.4% GT1, 12.6% GT2, 10.2% GT3, 1.5% GT4, and 0.3% GT5/6, and the global distribution is approximately 46% GT1, 13% GT2, 22% GT3, 13% GT4, 1% GT5, 2% GT6, and 3% undefined genotypes [ 35 , 36 ]. The median viral load of the HCV samples in this work (6.97 log 10 cp/mL) was similar to the median viral load of 6.3 log 10 IU/mL that was reported in a survey of HCV-positive individuals across 20 clinical trials with enrolled patients from 36 different countries spread across the Americas, Asia, Europe, Africa, and Australia [ 39 ]. In this work, viral loads and RNA concentrations are described in terms of copies rather than international units (IU) due to the method of quantification of the RNA standards used in RT-qPCR.…”

Determining the lower limit of detection required for HCV viral load assay for test of cure following direct‐acting antiviral‐based treatment regimens: Evidence from a global data set

“…Most of the included cohorts have been well described in the literature 19–26 . Table 1 summarizes key characteristics of these cohorts, including number of HCV‐treated patients, gender, age, and genotype distribution, DAA regimens and the proportion who achieved SVR following treatment.…”

“…Most of the included cohorts have been well described in the literature. [19][20][21][22][23][24][25][26] Table 1 summarizes key characteristics of these cohorts, including number of HCV-treated patients, gender, age, and genotype distribution, DAA regimens and the proportion who achieved SVR following treatment. There was a high degree of heterogeneity in patient characteristics across cohorts, reflecting varying HCV epidemic profiles in different countries.…”