Sofosbuvir/Velpatasvir Pharmacokinetics, Safety, and Efficacy in Pregnant People with Hepatitis C Virus.

Abstract

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).