Daily treatment with the antiviral drug tenofovir during the third trimester of pregnancy reduced the mother-to-child transmission rate of hepatitis B (HBV) from 18 percent to 5 percent, according to the findings of a clinical trial led by researchers from NYU Langone Medical Center and published on June 16 in the New England Journal of Medicine.
The study focused on the most common way that children become infected with hepatitis B, an incurable viral infection that causes liver disease and cancer, which is through infection during the perinatal period. Without intervention, 80 to 90 percent of infants who are born to mothers infected with hepatitis B develop a chronic infection. The current standard of care is to provide vaccine and immune globulin to reduce transmission rates.
“Preventing mother-to-child transmission is the most effective way to reduce the global burden of chronic hepatitis B infection and liver cancer,” says Calvin Pan, MD, lead author of the study and a clinical professor of medicine at NYU Langone. “We believe that these findings will not only save many lives, but could also help to eradicate hepatitis B nationally and abroad.”
The study was conducted in five locations in China, where HBV infection is endemic. Pan and colleagues enrolled 200 pregnant women with a high “viral load,” defined as one million copies of the virus per milliliter in a blood sample. Participants were randomly assigned to either a control group that received no antiviral therapy, or to a second group that received a daily dose of 300 milligrams of tenofovir in pill form, beginning at 30 or 32 weeks of pregnancy and continuing until 4 weeks after delivery.
Treatment effectively reduced the viral load of the pregnant women, says Pan. Before delivery, 68 percent of tenofovir-treated mothers had HBV loads below 1 million copies per milliliter, compared to 2 percent of nontreated mothers.
In terms of safety, researchers found that tenofovir was well tolerated; only one participant treated with tenofovir voluntarily withdrew from the study due to nausea. Among the children born during the study, Pan and his colleagues found no significant differences between the tenofovir-treated group and the control group with regard to fetal development and infant growth.
“This study provides strong evidence on how best to care for women infected with hepatitis B during pregnancy and reduce the rate of disease transmission,” says Mark Pochapin, MD, the Sholtz/Leeds Professor of Gastroenterology and director of the Division of Gastroenterology and Hepatology at NYU Langone.
Based on the findings, the investigators recommend that women be tested for HBV viral load at week 28 of pregnancy. Those with a high viral load should receive tenofovir treatment starting at gestational week 30 until delivery to reduce the risk of transmission to their infants. In addition, infants should receive hepatitis B vaccine and immune globulin. Moving forward, longer term, observational studies are needed to confirm the safety of fetal exposure to tenofovir treatment, says Pan.
This research was supported by Gilead Sciences.
Dr. Pan’s co-authors were Zhong Ping Duan at Beijing Youan Hospital, Capital Medical University, in Beijing; Er Hei Dai and Bao Shen Zhu at Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang; Shu Qing Zhang and Wen Jing Zhao at Hepatobiliary Disease Hospital of Ji Lin Province, Changchun; Guo-Rong Han and Hong-Xiu Jiang at Second Affiliated Hospital of Southeast University, Nanjing; Yuming Wang at Institute for Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing; Huai Bin Zou at Youan Hospital, Capital Medical University, Beijing; and Huai Hong Zhang at Nanyang Center Hospital, Nanyang, Henan, all for the China Study Group for the Mother-to-Child Transmission of Hepatitis B.
This news release describes a clinical trial testing whether an antiviral drug given to pregnant women in their third trimester reduces their hepatitis B viral load. The study also examined whether the drug limits the transmission of the virus from mother to baby. The answers to both questions are yes, suggesting a new strategy for dealing with the spread of this disease.
The release does a good job describing harms, quantifying benefits and describing the study protocol. Because the cost of hepatitis drugs has been widely debated for the past few years, a mention of the drug’s cost would have made the release stronger.
Almost 240 million people are infected with hepatitis B virus and about 780,000 die each year from the disease, according to the World Health Organization. The hepatitis B virus infects the liver and while many recover with treatment, it can become a chronic infection. Babies and young children infected with the virus are more likely to develop chronic hepatitis B. If administering a drug to infected mothers reduces the proportion of newborns getting the disease, it would be a considerable improvement in public health.
The release makes no mention of the cost of the drug in question, Tenofovir. A web search found that the cost for a month’s supply of the antiviral drug averages just over $1,000. For some patients, that cost may be prohibitive. The cost is an issue of particular concern for developing countries, but it is also true that the price may be much lower for them than in the United States. Many pharmaceutical companies offer their drugs at steeply discounted rates in poorer countries to expand access to life-saving medicines.
The release clearly says that 68 percent of women receiving the drug reduced their viral load while only 2 percent of the women in the control group had that success. It also says that the transmission of hepatitis B from mother to newborn dropped from 18 percent to 5 percent, an important clinical outcome.
The release includes a discussion of harms. It states that “tenofovir was well tolerated; only one participant treated with tenofovir voluntarily withdrew from the study due to nausea.” It also says that researchers “found no significant differences between the tenofovir-treated group and the control group with regard to fetal development and infant growth.” Lastly, it calls for longer term, observational studies to confirm the safety of fetal exposure to tenofovir treatment.
The release provides a good overview of the randomized, placebo-controlled trial which was undertaken to gauge the efficacy of the drug in both reducing the viral load of hepatitis-B-positive mothers and reducing the rate of transmission of the disease from mother to newborn. It offers solid, numerical evidence of both outcomes. It describes the number of patients (200 pregnant women), defined what constituted a “high” viral load, and described the approximate length of treatment. It did omit a mention of whether the trial was blinded.
This release does not commit disease mongering.
The release notes that the research is funded by Gilead Sciences. It should also have mentioned that a corresponding author disclosed speaking and advising fees from Gilead, according to the published study.
The release is comparing the use of an antiviral drug given to pregnant women versus the normal procedure of giving both a vaccine and immune globulin.
The release doesn’t mention that tenofovir (marketed as Viread), the drug being tested, is already an FDA approved drug so many readers may not know that it’s available. It was approved by the FDA in 2001 for HIV and in 2008 for chronic hepatitis B.
The release just barely implies novelty with this statement which suggests a change in treating infected women who are pregnant:
“Based on the findings, the investigators recommend that women be tested for HBV viral load at week 28 of pregnancy. Those with a high viral load should receive tenofovir treatment starting at gestational week 30 until delivery to reduce the risk of transmission to their infants.”
While the drug itself isn’t novel, positive outcomes from a controlled trial on pregnant women carrying the virus does seem to introduce a new treatment approach.
This release does not use any unjustifiable language.