MINMON试验中丙型肝炎病毒治疗采用最小监测方法后的再感染及耐药相关替代突变

Reinfection and Resistance Associated Substitutions Following a Minimal Monitoring Approach for Hepatitis C Virus Treatment in MINMON Trial.

作者信息

Han Win Min, Solomon Sunil Suhas, Smeaton Laura, Avihingsanon Anchalee, Wagner Cardoso Sandra, Li Jiani, Parvangada Aiyappa, Sulkowski Mark, Naggie Susanna, Martin Ross, Mo Hongmei, Maiorova Evguenia, Wyles David

机构信息

The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Thai Red Cross AIDS Research Centre, Pathum Wan, Bangkok, Thailand.

Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia.

出版信息

Clin Infect Dis. 2025 Jul 18;80(6):1293-1301. doi: 10.1093/cid/ciae627.

DOI:10.1093/cid/ciae627

PMID:39702964

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12272843/

Abstract

BACKGROUND

Simplified approaches to hepatitis C virus (HCV) treatment delivery are needed to meet elimination goals. However, the impact of low-touch strategies on individuals at higher risk due to treatment failure or reinfection is unknown. We estimated HCV reinfection rates, and the impact of resistance associated substitutions (RASs) on response in the ACTG A5360 (MINMON) trial.

METHODS

HCV RNA evaluations were scheduled at weeks 0, 24 (sustained viral response [SVR] visit), 48, and 72. Participants with post-entry HCV RNA ≥ lower limit of quantification (LLoQ) had deep sequencing of NS5A and NS5B genes performed. Phylogenetic analysis distinguished between reinfection and treatment failure. Reinfection rates per 100 person-years (PYS) were calculated with 95% confidence interval (CI) constructed using Poisson distribution.

RESULTS

Of 397 participants with post-entry HCV RNA, 29 had ≥LLoQ and available sequencing data. Of those 29, 5 participants initially designated as non-SVR, and 12 participants initially attaining SVR (evaluated at week 24) were determined to have reinfections (total 17 reinfections) (reinfection rate 3.9/100 PYS [95% CI, 2.4-6.2]). All 17 participants with HCV reinfection were male (13 MSM and 15 with HIV). Of 29 had ≥LLoQ, 12 were identified as treatment failure. SVR (excluding reinfections) in presence and absence of baseline RAS was 93.5% (43/46) and 97% (337/346), respectively, with an overall SVR rate of 97.0% [95% CI, 94.8-98.3] (385/397).

CONCLUSIONS

Accounting for reinfections, SVR in MINMON was 97.0% further supporting simplified HCV treatment. No significant difference in SVR was found by baseline velpatasvir RAS. The high reinfection rate, especially among men who have sex with men (MSM) with human immunodeficiency virus (HIV), underscores the need to scale-up evidence-based interventions to reduce reinfection.

CLINICAL TRIALS REGISTRATION

NCT03512210.

摘要

背景

需要简化丙型肝炎病毒（HCV）治疗方案以实现消除目标。然而，低接触策略对因治疗失败或再感染而处于较高风险的个体的影响尚不清楚。我们在ACTG A5360（MINMON）试验中估计了HCV再感染率以及耐药相关替代（RAS）对治疗反应的影响。

方法

在第0、24周（持续病毒学应答[SVR]访视）、48周和72周安排HCV RNA评估。入组后HCV RNA≥定量下限（LLoQ）的参与者对NS5A和NS5B基因进行深度测序。系统发育分析区分再感染和治疗失败。每100人年（PYS）的再感染率通过使用泊松分布构建的95%置信区间（CI）计算。

结果

在397名入组后有HCV RNA的参与者中，29名有≥LLoQ且有可用的测序数据。在这29名参与者中，5名最初被指定为非SVR，12名最初达到SVR（在第24周评估）的参与者被确定为再感染（共17例再感染）（再感染率3.9/100 PYS [95% CI，2.4 - 6.2]）。所有17例HCV再感染的参与者均为男性（13名男男性行为者和15名合并HIV感染者）。在29名有≥LLoQ的参与者中，12名被确定为治疗失败。有和无基线RAS时的SVR（不包括再感染）分别为93.5%（43/46）和97%（337/346），总体SVR率为97.0% [95% CI，94.8 - 98.3]（385/397）。