Antiviral Combo Shows Early Promise Against HCV in Pregnancy

By Scott Baltic

August 07, 2020

NEW YORK (Reuters Health) - The combination of ledipasvir and sofosbuvir appears to be safe and effective in treating pregnant women infected with genotype 1 hepatitis C virus (HCV), curing all nine participants in a new phase-1 trial.

In addition, there were no clinically significant differences in drug exposure between the pregnant patients and a reference group of non-pregnant women, researchers report in The Lancet Microbe.

"This study was the first step towards creating a clinical pathway for HCV treatment in pregnancy by showing that no dose change is needed," said Dr. Catherine Chappell of the Magee-Womens Hospital of the University of Pittsburgh Medical Center, in Pennsylvania.

"Pregnancy is a window of opportunity for HCV testing and treatment, because of increased healthcare engagement, unique psychological motivation, and the possibility of preventing transmission of HCV to the baby," she told Reuters Health by email. "All of these factors would likely lead to better adherence to medication, leading to an almost guaranteed cure."

The previous standard HCV therapy, pegylated interferon plus ribavirin, was considered too risky for use during pregnancy, Dr. Chappell and colleagues note, because of "high toxicity, substantial side-effects, and teratogenicity risks." They believe theirs is the first clinical trial of the current standard, ledipasvir plus sofosbuvir (Harvoni, Gilead Sciences), in pregnant women.

The researchers enrolled nine patients ages 25-38 (median age, 31) in an open-label pharmacokinetic study; all were white, were between 23 and 24 weeks' gestation, and eight were Medicaid insured.

Seven of nine were tobacco users, and the same number had used marijuana, cocaine, methamphetamines and/or opioids in the past year. Four were on opioid maintenance therapy. Six of nine had traded sex for drugs.

Ledipasvir-sofosbuvir is approved only for HCV genotypes 1, 4, 5 and 6. Accordingly, the study cohort included only patients with genotype 1 infection.

Each participant received a 12-week course of once-daily Harvoni (ledipasvir 90 mg plus sofosbuvir 400 mg). Twelve weeks after completing the treatment, all nine participants met the definition of HCV cure with undetectable viral loads.

Most adverse events were grade 1; none resulted in treatment discontinuation.

Eight of the nine infants were delivered at term (37 weeks or more gestation), and all nine had normal birth weights (>2500 g). None had detectable HCV RNA at birth or during 12 months of follow-up.

Dr. Nezam Afdhal, chief of gastroenterology at Beth Israel Deaconess Medical Center, in Boston, and professor of medicine at Harvard Medical School, said this was "a small, well performed Phase 1 study."

"Safety of medications is always the key issue in pregnancy, and treatment was started in the 3rd trimester to minimize potential harm to the fetus," Dr. Afdhal, who was not involved in the study, told Reuters Health by email. "However, it would require large studies with follow-up post-delivery to truly confirm safety, and this would be challenging."

Dr. Kris V. Kowdley, director of Liver Institute Northwest, in Seattle, and clinical professor at the Elson S. Floyd College of Medicine, Washington State University, told Reuters Health by email, "The increase in injection drug use among pregnant women has led to an increased rate of maternal-child transmission of HCV. It is therefore important to obtain data about the safety and efficacy of direct-acting antiviral drugs for hepatitis C in pregnant women."

He said the study was "an important step forward in treating pregnant women with HCV" and "will have implications for the health of the pregnant woman and in reducing the risk of transmission to her child." Dr. Kowdley was not involved in the research either.

This study was supported by the National Institutes of Health and Gilead Sciences. Dr. Chappell and several coauthors report financial ties to the company.

SOURCE: The Lancet Microbe, online July 27, 2020.