کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2509865 | 1557830 | 2015 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Long-term follow-up of patients receiving boceprevir for treatment of chronic hepatitis C Long-term follow-up of patients receiving boceprevir for treatment of chronic hepatitis C](/preview/png/2509865.png)
• SVR was durable in most patients treated with boceprevir plus peginterferon and ribavirin.
• 73% of RAVs that develop during boceprevir treatment revert to WT within 3 years.
• Time to return to WT is associated with the phenotype of RAV.
The durability of sustained virologic response (SVR) following boceprevir-based therapy in patients with hepatitis C virus (HCV) infection has not been reported. Furthermore, in patients receiving protease inhibitor-based therapies, development of resistance can contribute to treatment failure. The aim of the present study was to follow the clinical progression of patients treated with boceprevir after treatment in phase 2/3 clinical trials.This was a 3-year, long-term follow-up analysis of patients enrolled in boceprevir phase 2/3 studies. No treatment was administered during follow-up. Patients with SVR were assessed for durability of viral eradication. Non-SVR patients with on-treatment resistance-associated variants (RAVs) were assessed for longevity of RAVs.A total of 1148 patients (SVR, n = 696; virologic failure, n = 452) were enrolled in this follow-up analysis. The median duration of follow-up was approximately 3.4 years (range of 0.0–4.1 years). Overall, 3 of 696 patients with SVR had detectable HCV RNA during the follow-up period (relapse rate of 0.4% or 1.3 relapses/1000 person-years). The majority of patients who developed RAVs during the initial treatment study (228/314, 73%) reverted to wild-type (WT) within 3 years (RAVs persisted in 27% of patients). The median time for all RAVs to become undetectable was 1.11 years (95% confidence interval 1.05–1.20 years). V36M, T54A, A156S, I/V170A and V36M + R155K appeared to have a faster rate of return to WT (median times to return to WT of ⩽0.9 years); whereas, T54S, R155K, V55A and T54S + R155K had a slower rate of return to WT (median times to return to WT of approximately 1.1 years). Return to WT appeared slightly faster in patients with G1b RAVs compared to those with G1a RAVs, and in patients with previous non-response or relapse versus breakthrough or incomplete virologic response.SVR was durable in most patients treated with boceprevir. Furthermore, most RAVs present at the time of virologic failure reverted to WT over time. Time to return to WT was associated with the phenotype of RAV, presumably a reflection of the fitness of the mutant virus, suggesting that HCV RAVs are not permanently archived, but are replaced in the viral population by WT virus.
Journal: Antiviral Research - Volume 113, January 2015, Pages 71–78