Pharmacokinetics of Sofosbuvir and Velpatasvir for Hepatitis C Treatment in Pregnancy

Background: Pregnancy is a time when women are uniquely engaged with the healthcare system and are often motivated to participate in activities directed toward improvement of their own health and ensuring the health of their unborn child, which also provides an opportunity for healthcare interventions such as treatment for hepatitis C virus (HCV) infection. Methods: This was a multi-site, prospective, open-label, pharmacokinetic (PK) study conducted at two large maternity hospitals in Melbourne, Australia, to evaluate the safety and pharmacokinetics of antenatal sofosbuvir (SOF) and velpatasvir (VEL) treatment administered for 12 weeks during the second and third trimester. Five women were recruited and underwent detailed PK assessments across three visits. Results: Compared to historical data in non-pregnant women, SOF area under the concentration curve (AUC) and maximum concentrations (Cmax) were 60% and 49% higher in pregnancy, respectively. In contrast, exposure to the inactive metabolite of SOF, GS-331007, was 43% lower in pregnancy. Both Cmax and AUC for VEL in pregnancy were similar to values reported in historic non-pregnant women (~21% lower in pregnant women). SOF/VEL was safe and well tolerated. Conclusions: These results add to the limited published experience prescribing antivirals in pregnancy and provide further support for a larger ongoing prospective study and other efforts to support HCV treatment in pregnancy.