Thank you for your interest in CCO content. As a guest, please complete the following information fields. These data help ensure our continued delivery of impactful education.
Become a member (or login)? Member benefits include accreditation certificates, downloadable slides, and decision support tools.
Available data on the safety of DAAs in pregnancy are limited, as discussed earlier. Animal data are available for some of the medications currently in common use. For studies involving ledipasvir/sofosbuvir (LDV/SOF) and glecaprevir/pibrentasvir, there is no evidence of significant birth defects following administration to pregnant rats. However, there was an increase in visceral malformations when velpatasvir was given alone to pregnant rabbits. It is important to note that investigators used very high doses of the medications in these studies—much higher than what would be used in humans.
Although the letter-based classification system that graded medications from A through D in terms of pregnancy risk is no longer in use by the FDA, LDV/SOF was previously considered pregnancy category B, which meant that animal reproduction studies failed to demonstrate a risk to the fetus, but there are no adequate and well-controlled studies in pregnant women.
This slide outlines the first published study of HCV treatment with DAA therapy in pregnant women. This was an open-label, phase I pharmacokinetic study of LDV/SOF for 12 weeks in pregnant women with genotype 1, 4, 5, or 6 HCV who entered the study during the second and third trimesters of pregnancy. Because the investigators used a regimen that excluded enrollment of patients with HCV genotype 2 or 3, enrollment was somewhat hindered. Nonetheless, they were able to enroll 9 patients and had complete follow-up on 8 of those 9 patients. One patient was excluded from the primary endpoint pharmacokinetic analysis due to nonadherence to the dosing schedule. Plasma HCV RNA at enrollment ranged from 1.0 x 10⁵ to 73.5 x 10⁵ copies/mL; only 1 participant had HCV RNA > 6 x 10⁵ copies/mL.
All of the women who had complete follow-up achieved sustained virologic response at 12 weeks posttreatment (SVR12; n = 9). This demonstrated that the medication was effective when used in pregnancy. Although some adverse events were recorded, they were mild (grade 1-2). The infants born during this study reached a median gestational age of 39 weeks and all had normal birth weights. None had HCV RNA in cord blood, nor was HCV RNA detected through 12 months of follow-up.
Therefore, although this is a very small study, it supports the concept that DAA therapy can likely be safely and effectively used during pregnancy. Of course, larger studies are needed to provide more safety and efficacy data. Indeed, larger studies are underway and planned to evaluate the safety and efficacy of other HCV DAA regimens during pregnancy, including the pangenotypic regimen sofosbuvir/velpatasvir.
To conclude, there has been an increase in HCV incidence among women of childbearing age and a concomitant increase in HCV among women during pregnancy. This is very closely tied to the opioid epidemic in the United States.
Guidelines have been updated to recommend HCV screening for all pregnant women, not just women with identifiable risk factors. Treatment for HCV is recommended before pregnancy for women of childbearing age. HCV treatment during pregnancy is not currently recommended but can be considered on an individual basis.
Regarding MTCT of HCV infection, rates are approximately 6% in women with HCV monoinfection, but coinfection with HIV significantly increases the risk of transmission to approximately 11%. Because of an increase in women with HCV infection and the risk of MTCT, there has also been an increase in HCV infection rates among children. The challenge is that children born to mothers with HCV infection are not always tested.
All children of mothers with HCV should be tested for the HCV Ab at 18 months of age; if they test positive, they should be referred to a HCV specialist for treatment. Treatment with HCV DAA therapy is recommended in children as young as 3 years of age.
Preliminary data from animal studies and 1 small study of pregnant women suggest that some DAAs are likely to be generally safe in pregnancy. Studies are underway to more definitively determine the safety and efficacy of DAA therapy during pregnancy.