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 (SOF)/velpatasvir (VEL) in pregnant versus nonpregnant people.

Methods: Pregnant people with chronic HCV infection were enrolled between 23 and 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 (DBSs) were measured and compared to historical data in nonpregnant people. Maternal adverse events, delivery outcomes, the sustained virologic response 12 weeks after therapy, 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 nonpregnant 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 DBSs was approximately 50% lower in pregnant versus nonpregnant people. All 10 participants who completed treatment had undetectable HCV RNA at delivery. Two participants were lost to follow-up after delivery, but 1 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.