Akiyama Matthew J, Riback Lindsey, Reeves Jacqueline D, Lie Yolanda S, Agyemang Linda, Norton Brianna L, Arnsten Julia H, Litwin Alain H
Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NEW YORK, USA.
Monogram Biosciences, LabCorp, South San Francisco, California, USA.
Open Forum Infect Dis. 2021 Sep 30;8(10):ofab474. doi: 10.1093/ofid/ofab474. eCollection 2021 Oct.
Resistance-associated substitutions (RASs) to HCV direct-acting antivirals (DAAs) can contribute to virologic failure and limit retreatment options. People who inject drugs (PWID) are at highest risk for transmission of resistant virus. We report on RASs at baseline and after virologic failure in DAA-naive and protease inhibitor-experienced PWID.
We sequenced the NS3/4A, NS5A, and NS5B regions from 150 PWID with genotype 1 (GT1) viruses; 128 (85.3%) GT1a, 22 (14.7%) GT1b.
Among the 139 (92.7%) DAA-naive PWID, 85 of 139 (61.2%) had baseline RASs-67 of 139 (48.2%) in NS3 (predominantly Q80K/L); 25 of 139 (18.0%) in NS5A; and 8 of 139 (5.8%) in NS5B. Of the 11 protease inhibitor-experienced participants, 9 had baseline NS3 RASs (V36L N = 1, Q80K N = 9) and 4 had baseline NS5A RASs (M28V N = 2, H58P N = 1, A92T N = 1). Among the 11 participants who had posttreatment samples with detectable virus (7 treatment failures, 1 late relapse, 3 reinfections), 1 sofosbuvir/ledipasvir failure had a baseline H58P. Two sofosbuvir/ledipasvir-treated participants developed new NS5A mutations (Q30H, Y93H, L31M/V). Otherwise, no RASs were detected.
Our results demonstrate RAS prevalence among DAA-naive PWID is comparable to that in the general population. Only 2 of 150 (1.3%) in our longitudinal cohort developed treatment-emergent RASs. Concern for transmission of resistant virus may therefore be minimal.
丙型肝炎病毒（HCV）直接抗病毒药物（DAA）的耐药相关替代（RAS）可导致病毒学失败并限制再治疗选择。注射吸毒者（PWID）感染耐药病毒的风险最高。我们报告了初治和有蛋白酶抑制剂治疗史的PWID在基线和病毒学失败后的RAS情况。
我们对150例感染1型（GT1）病毒的PWID的NS3/4A、NS5A和NS5B区域进行了测序；其中128例（85.3%）为GT1a，22例（14.7%）为GT1b。
在139例（92.7%）初治的PWID中，139例中有85例（61.2%）有基线RAS——139例中有67例（48.2%）在NS3区域（主要为Q80K/L）；139例中有25例（18.0%）在NS5A区域；139例中有8例（5.8%）在NS5B区域。在11例有蛋白酶抑制剂治疗史的参与者中，9例有基线NS3 RAS（V36L 1例，Q80K 9例），4例有基线NS5A RAS（M28V 2例，H58P 1例，A92T 1例）。在11例治疗后样本中病毒可检测到的参与者（7例治疗失败，1例晚期复发，3例再感染）中，1例索磷布韦/维帕他韦治疗失败患者有基线H58P。2例接受索磷布韦/维帕他韦治疗的参与者出现了新的NS5A突变（Q30H、Y93H、L31M/V）。除此之外，未检测到RAS。
我们的结果表明，初治PWID中RAS的流行率与普通人群相当。在我们的纵向队列中，150例中只有2例（1.3%）出现了治疗中出现的RAS。因此，对耐药病毒传播担忧可能极小。
