Background Simplified approaches to 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%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 MSM with HIV, underscores the need to scale-up evidence-based interventions to reduce reinfection.

中文翻译：

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在 MINMON 试验中，HCV 治疗的最低监测方法后的再感染和耐药相关替代


背景 需要简化的 HCV 治疗方法来实现消除目标。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。在 ACTG A5360 （MINMON） 试验中，我们估计了 HCV 再感染率以及耐药相关替代 （RAS） 对反应的影响。方法 HCV RNA 评估安排在第 0 周、第 24 周 （持续病毒反应 [SVR] 访视）、第 48 周和第 72 周进行。进入后 HCV RNA ≥定量下限 （LLoQ） 的参与者对 NS5A 和 NS5B 基因进行了深度测序。系统发育分析区分再感染和治疗失败。每 100 人年再感染率 （PYS） 使用泊松分布构建的 95% CI 计算。结果 在 397 名进入后 HCV RNA 的参与者中，29 名具有 ≥LLoQ 和可用的测序数据。在这 29 名参与者中，5 名最初被指定为非 SVR 的参与者和 12 名最初达到 SVR 的参与者（在第 24 周评估）被确定为再感染（共 17 次再感染）（再感染率 3.9/100 PYS [95%CI 2.4-6.2]）。所有 17 名 HCV 再感染参与者均为男性 （13 名 MSM 和 15 名 HIV 感染者）。在 29 例 ≥LLoQ 患者中，12 例被确定为治疗失败。存在和不存在基线 RAS 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）。结论 考虑到再感染，MINMON 的 SVR 为 97.0%，进一步支持简化的 HCV 治疗。基线 velpatasvir RAS 未发现 SVR 存在显著差异。高再感染率，尤其是在感染 HIV 的 MSM 中，凸显了扩大循证干预措施以减少再感染的必要性。