Direct antiviral agents (DAAs) and their use in pregnant women with hepatitis C (HCV)

ABSTRACT

Introduction

Direct-Acting Antiviral Agents (DAAs) provide safer, efficacious, tolerable, and curative therapy for women with hepatitis C. Their preferred safety and efficacy profile make them potential therapies for the elimination of perinatal transmission of hepatitis C virus (HCV). However, DAAs are not currently recommended for use during pregnancy due to limited pharmacokinetic and safety data.

Areas Covered

This review covers the different DAA drug combinations, the available data on their pharmacodynamic and pharmacokinetic properties, how the physiology in pregnancy can potentially affect DAA drug disposition, known drug–drug interactions with DAAs, and available and planned epidemiological and pharmacokinetic studies on DAA use during pregnancy. Although no large randomized clinical trials or prospective cohort studies involving DAAs have been completed in pregnancy, the currently available studies demonstrate no significant changes in pharmacokinetics, and no major safety concerns in women with hepatitis C.

Expert Opinion

Initial pharmacokinetic and safety data suggest that DAAs have high efficacy and a low risk of adverse events during pregnancy. As more pharmacokinetic and epidemiologic data become available, DAAs could become a preferred option for treating HCV during pregnancy and elimination of perinatal transmission of hepatitis C virus.

KEYWORDS:

• Hepatitis C virus
• pregnancy
• direct antiviral agents
• pharmacodynamics
• pharmacokinetics
• pharmacoepidemiology

Article highlights

• Hepatitis C virus (HCV) infection continues to be a critical public health problem. In pregnant women, approximately 3-6% of infants born to HCV positive women become infected.

• Recent advancements in direct antiviral agent (DAA) therapy have made many more efficacious and tolerable treatment options available. However, DAAs are not currently recommended for use during pregnancy due to limited pharmacokinetic and safety data.

• Pregnancy represents an ideal window of opportunity for HCV DAA therapy given that pregnancy is a time of high healthcare engagement, enhanced insurance coverage, and improved adherence to antiviral therapy (as evidence has demonstrated with the use of antiretroviral therapy to prevent perinatal transmission of HIV)

• Despite these potential advantages, the continued interval and dearth of information about the effects of medication use during pregnancy and the ways in which pregnancy alters pharmacokinetics and drug response that exist from when a drug receives first licensure in the adult population and when pregnancy safety, pharmacokinetic, pharmacodynamic and efficacy data become available, has led to large gaps on what we know and understand about DAA use in pregnant women with HCV infection

• Expanding HCV therapy to pregnant women will not only lower barriers to care and further hepatocellular carcinoma elimination goals, but may reduce perinatal transmission of hepatitis C of the incident pregnancy, and will potentially eliminate vertical HCV transmission risk to subsequent pregnancies.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed advisory and research support from Gilead and advisory for Abbvie. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the National Institutes of Health (NIH) under the Award Number K23HD104517. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.