Both mothers and infants do well in pilot study
SEATTLE – Treating pregnant women diagnosed with hepatitis C infection with a potent 12-week course of direct-acting antivirals achieved sustained virologic responses — a functional cure of the disease — and did not appear to harm their babies, researchers reported here.
“In our pilot study, we treated nine women, who all completed the study and delivered healthy babies,” said Catherine Chappell, MD, of the University of Pittsburgh Medical Center Magee-Womens Hospital. “Eight of the women have completed the sustained virologic response assessment, and one woman is still being followed. Of the nine infants enrolled in the study, five have completed the 1-year follow-up, and four are still being followed.”
At a press conference at the annual Conference on Retroviruses and Opportunistic Infections, Chappell said, “In this first study of hepatitis C virus treatment during pregnancy, ledipasvir/sofosbuvir (Harvoni) administration was safe for pregnant women and effective for hepatitis C virus cure. All the patients were cured of hepatitis C virus infection and all infants are negative to date.”
She said that all the adverse events that occurred related to treatment were mild or moderate, and there were no safety concerns to date after ledipasvir/sofosbuvir in utero exposure.
Asked for his perspective, Robert Schooley, MD, of the University of California, San Diego, who was not involved with the study, told MedPage Today: “This is a pilot study. It makes the point that women who are pregnant and are diagnosed with hepatitis C virus can tolerate the drug treatment during pregnancy. Now we need to design more definitive trials to make sure lower incident side effects or toxicities are not seen as the experience is extended to larger numbers of women and their babies,” Schooley continued. “So far the experience has been really good, but there are just nine patients in this study so we have to be cautious which such a low ‘n.'”
Chappell noted that about 2% of women delivering babies at Magee-Womens Hospital are diagnosed with hepatitis C infection, and the number is rising, probably due to the increasing opioid epidemic in the U.S. “Of the 200 pregnant women a year diagnosed with hepatitis C virus, 5.8% transmit the virus to their newborns – more than 10 infants a year are infected with the virus at birth,” she said.
She explained that the researchers had hoped to show in the pilot study that treating the women for 12 weeks with the direct-acting antiviral combination of ledipasvir/sofosbuvir would clear the virus and be safe for both mother and child.
The team screened 29 patients for the study, but five were excluded because their strain of hepatitis C virus was genotype 2, five others were excluded because their virus was genotype 3, four were eliminated because of ongoing drug use, three women declined to participate, two pregnant women said they were not planning to deliver at the participating hospital, and one women had a high aspartate aminotransferase-to-platelet ratio index score, indicating the likelihood of liver fibrosis.
The trial admitted only women with genotypes, 1, 4, 5, and 6. All the participants were diagnosed with genotype 1 hepatitis C virus infections. The women also had be delivering a single baby, and be free of co-infection with HIV or hepatitis B virus infection.
Women were excluded from the study if they had undergone previous treatment for hepatitis C virus with sofosbuvir or a NS5A inhibitor, if they had a history of cirrhosis, a history of or a high risk of spontaneous pre-term births, or if the women had significant laboratory findings at screening.
Characteristics for the nine women in the study were as follows:
- Median age was 31
- All were white
- Eight had public insurance, and one was insured through the military
- Two of the women had less than a high school education, and six had more than a high school education
- Eight of the women had been infected with hepatitis C infection through intravenous drug use, and one had been infected perinatally
“Larger studies must be conducted to confirm the safety and efficacy of hepatitis C virus treatment during pregnancy,” Chappell said. “Further studies should consider evaluation of pan-genotypic regimens for pregnancy.”
Chappell disclosed relevant relationships with Gilead Sciences and Merck.
Schooley disclosed relevant relationships with Gilead Sciences.
Conference on Retroviruses and Opportunistic Infections
Source Reference: Chappell C, et al “A Phase 1 study of ledipasvir/sofosbuvir in pregnant women with hepatitis C virus” CROI 2019.