Background Treatment of hepatitis C virus (HCV) during pregnancy can cure maternal HCV and prevent perinatal HCV transmission. The primary objective was to compare the pharmacokinetics (PK) of sofosbuvir/velpatasvir (SOF/VEL) in pregnant versus nonpregnant people. Methods Pregnant people with chronic HCV infection were enrolled between 23-25 weeks’ gestation and were provided SOF/VEL daily for 12 weeks. PK visits were performed at 3, 6 and 9 weeks. VEL, SOF and GS-331007 (the inactive metabolite of SOF) in plasma and the SOF active metabolite (007-TP) in peripheral blood mononuclear cells (PBMCs) and dried blood spots (DBS) were measured and compared to historical data in non-pregnant people. Maternal adverse events, delivery outcomes, the sustained virologic response 12 weeks after therapy (SVR12), infant adverse events and HCV perinatal transmission were assessed. Results Fourteen participants were screened, and 11 enrolled. One participant discontinued treatment due to worsening of hyperemesis. VEL area under the curve (AUC) was similar to historic data in non-pregnant people, but the AUCs of SOF and GS-331007 were 38% higher and 38% lower, respectively. Concentrations of 007-TP in PBMCs were comparable or higher, whereas 007-TP in DBS were ∼50% lower in pregnancy vs. non-pregnant people. All 10 participants who completed treatment had undetectable HCV RNA at delivery. Two participants were lost to follow-up after delivery, but one had an HCV RNA through clinical care. All participants with data were cured (N=9) and none of the infants acquired HCV (N=8). Conclusions SOF/VEL exposures were not clinically different in pregnancy and support further evaluation of antenatal SOF/VEL treatment. Funding This study was supported by the NIH (R21HD101996), NIH/OWHR (K12HD043441), and Gilead Sciences (IN-US-342-5634).

中文翻译：

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Sofosbuvir/Velpatasvir 在丙型肝炎病毒孕妇中的药代动力学、安全性和有效性


背景 妊娠期间治疗丙型肝炎病毒 （HCV） 可以治愈母体 HCV 并防止围产期 HCV 传播。主要目的是比较 sofosbuvir/velpatasvir （SOF/VEL） 在孕妇和非孕妇中的药代动力学 （PK）。方法 在妊娠 23-25 周之间纳入慢性 HCV 感染孕妇，每天提供 SOF/VEL，持续 12 周。在 3 、 6 和 9 周进行 PK 访视。测量血浆中的 VEL、SOF 和 GS-331007 （SOF 的非活性代谢物） 以及外周血单核细胞 （PBMC） 和 干血斑 （DBS） 中的 SOF 活性代谢物 （007-TP），并与非孕妇的历史数据进行比较。评估孕产妇不良事件、分娩结局、治疗后 12 周持续病毒学反应 （SVR12） 、婴儿不良事件和 HCV 围产期传播。结果 筛选了 14 名参与者，其中 11 名入组。1 名参与者因剧吐恶化而停止治疗。VEL 曲线下面积 （AUC） 与非孕妇的历史数据相似，但 SOF 和 GS-331007 的 AUC 分别高 38% 和 38%。PBMC 中 007-TP 的浓度相当或更高，而妊娠期 DBS 中的 007-TP 浓度比非妊娠者低约 50%。所有完成治疗的 10 名参与者在分娩时都检测不到 HCV RNA。两名参与者在分娩后失访，但一名参与者通过临床护理获得了 HCV RNA。所有有数据的参与者均已治愈 （N=9），无婴儿获得 HCV （N=8）。结论 妊娠期 SOF/VEL 暴露在临床上无差异，支持进一步评估产前 SOF/VEL 治疗。 资金 这项研究得到了 NIH （R21HD101996）、NIH/OWHR （K12HD043441） 和 Gilead Sciences （IN-US-342-5634） 的支持。