Department of Health, Law and Policy Management, Boston University School of Public Health, Boston, MA, USA.
Boston Medical Center, Section of Infectious Diseases, Boston University School of Public Health, Boston, MA, USA.
Adv Ther. 2021 Mar;38(3):1690-1700. doi: 10.1007/s12325-021-01647-4. Epub 2021 Feb 15.
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.
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.
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 IU/ml ± 0.8) compared to 9,585,957 IU/ml ± 8,247,669 (6.8 log 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 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 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 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 IU/ml ± 1.0).
At PTW12, 100% of virologic failures had an HCV RNA > 3.0 log IU/ml. The data are encouraging that with a LLOD of 3.0 log 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.
在实现世界卫生组织（WHO）消除丙型肝炎（HCV）全球治愈目标的过程中，尚存的障碍之一是缺乏既定的检测下限（LLOD），以确认接近患者的技术治疗后的治愈情况。在资源有限的环境中，通过即时检测（POCT）测定病毒学失败时的 LLOD 有助于提高检测可行性。
我们描述了在 20 项临床试验（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 和 APRI）中 69 名经历病毒学失败的患者的病毒血症水平。这些发现分为治疗期间、治疗后第 4 周（PTW4）或第 12 周（PTW12）失败。
在 5033 名患者的总体人群中，基线时 HCV RNA 平均水平为 4193712IU/ml ± 5955028（6.2 log IU/ml ± 0.8），而在 69 名在 PTW12 时发生病毒学失败的患者中，平均水平为 9585957IU/ml ± 8247669（6.8 log IU/ml ± 0.5）。所有患者病毒学失败时的 HCV RNA 平均水平为 6004980IU/ml ± 7077728（6.4 log IU/ml ± 0.7）。20 名患者在治疗期间发生病毒学失败，失败时的 HCV RNA 平均水平为 9136360IU/ml ± 8572113（6.7 log IU/ml ± 0.7），36 名患者在 PTW4 时复发，复发时的 HCV RNA 平均水平为 4131344IU/ml ± 5246954（6.3 log IU/ml ± 0.6），13 名患者在 PTW4 和 PTW12 之间复发，复发时的 HCV RNA 平均水平为 6376003IU/ml ± 7758968（6.3 log IU/ml ± 1.0）。
在 PTW12 时，100%的病毒学失败患者的 HCV RNA > 3.0 log IU/ml。这些数据令人鼓舞，即通过 LLOD 为 3.0 log IU/ml，POCT 可以准确识别所有治疗失败；需要更大规模的研究，包括真实世界的数据，来证实这些发现。
