Review article: direct‐acting antivirals for the treatment of HCV during pregnancy and lactation ‐ implications for maternal dosing, foetal exposure, and safety for mother and child

Abstract

Summary Background With the global efforts to eradicate hepatitis C virus (HCV), treatment during pregnancy is becoming a priority for research as this, and maternal cure should reduce vertical transmission. However, as information on the efficacy and safety of direct‐acting antivirals (DAAs) in pregnancy is generally lacking, treatment of HCV infection during pregnancy is not currently recommended. Aim To provide an overview of current knowledge regarding maternal exposure, placental handling and safety of DAAs during pregnancy and lactation Methods A literature search was performed focusing on the effect of pregnancy on maternal exposure to DAAs, the placental handling of DAAs, the safety of DAAs for mother and child during pregnancy and the safety of DAAs during lactation. Results Exposure to all DAAs studied is likely to be altered during pregnancy, mostly related to pregnancy‐induced effects on drug absorption and metabolism. Although animal studies show that most DAAs are reported to cross the placenta and transfer into breast milk, most DAA combinations show a favourable safety profile. Because of the rapid viral decline after treatment initiation, and to avoid the critical period of organogenesis, treatment may be started at the end of the second trimester or early third trimester. Conclusions Treatment of HCV infection during pregnancy is realistic, as DAAs are highly effective and treatment duration is relatively short. There is an urgent need to study DAAs during pregnancy and lactation to contribute to the goal of HCV elimination.

Sofosbuvir and daclatasvir compared with standard of care in the treatment of patients admitted to hospital with moderate or severe coronavirus infection (COVID-19): a randomized controlled trial

“…17 , 18 In a number of dose-ranging studies analysing sofosbuvir 19 , 20 and daclatasvir 21–25 individually or in combination with ribavirin and peginterferon alfa-2a compared with placebo, no progressive dose-related adverse events were observed. A recent review on sofosbuvir-containing regimens in pregnancy 26 concluded that DAAs have a favourable safety profile in pregnancy and suggests that a 12 week DAA course could be started at the end of the second or early third trimester. The safety of sofosbuvir and daclatasvir has even been proven in patients with severely impaired renal function.…”

Hepatitis C Virus Treatment in Children: A Challenge for Hepatitis C Virus Elimination

“…Ideally, a pan-genotypic, safe, and effective DAA combination would be available to all HCV-pregnant women living with HCV diagnosed by a (cost-effective) universal screening program. 44 Hepatitis C testing should be ordered at all routine clinic visits, such as antenatal checks and well-child and vaccination appointments to ensure that those diagnosed receive appropriate treatment. Obstetricians may play a key role by implementing universal testing for HCV in pregnant women, thereby enhancing the health of mothers and identifying children at risk.…”

Awareness and Prevalence of Hepatitis C Virus Infection Among Pregnant Women in Nigeria: A National Pilot Cross-Sectional Study

“…More so, HCV infection during pregnancy is associated with an increased risk of adverse fetal outcomes such as fetal growth restriction and low birth weight [3]. Therefore, there is need to intensify efforts at PMTCT of HCV [3,4].…”

“…Awareness of the risks associated with HCV infection during pregnancy among pregnant women will create more demands for HCV screening and PMTCT interventions among them. Some authorities have argued that routine antenatal screening for HCV is not a viable option in resourceconstrained settings because the information on the e cacy and safety of antivirals for HCV in pregnancy is generally lacking, and the treatment of HCV infection during pregnancy is not currently recommended [4,5]. Nevertheless, intrauterine and peripartum transmission of HCV are both possible and higher rates are associated with a high maternal serum viral load and concomitant HIV or HBV infection, prolonged or di cult delivery, and invasive fetal monitoring during delivery.…”

“…Hepatitis C virus prevalence in the maternal population mirrors that of the general population and obstetrics data could also help healthcare planners and caregivers to design and implement evidencebased interventions for HCV elimination [9]. The World Health Organization has called for HCV elimination as one of the major public health threat by 2030 [4]. Accordingly, the U.S. Preventive Services Task Force and the American Association for the Study of Liver Disease-Infectious Diseases Society of America 2019 guidelines recommend universal HCV screening for all individuals aged 18 years and older including pregnant women [4].…”