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Tenofovir versus Placebo to Prevent Perinatal Transmission of Hepatitis B.

ABSTRACT: BACKGROUND:Pregnant women with an elevated viral load of hepatitis B virus (HBV) have a risk of transmitting infection to their infants, despite the infants' receiving hepatitis B immune globulin. METHODS:In this multicenter, double-blind clinical trial performed in Thailand, we randomly assigned hepatitis B e antigen (HBeAg)-positive pregnant women with an alanine aminotransferase level of 60 IU or less per liter to receive tenofovir disoproxil fumarate (TDF) or placebo from 28 weeks of gestation to 2 months post partum. Infants received hepatitis B immune globulin at birth and hepatitis B vaccine at birth and at 1, 2, 4, and 6 months. The primary end point was a hepatitis B surface antigen (HBsAg)-positive status in the infant, confirmed by the HBV DNA level at 6 months of age. We calculated that a sample of 328 women would provide the trial with 90% power to detect a difference of at least 9 percentage points in the transmission rate (expected rate, 3% in the TDF group vs. 12% in the placebo group). RESULTS:From January 2013 to August 2015, we enrolled 331 women; 168 women were randomly assigned to the TDF group and 163 to the placebo group. At enrollment, the median gestational age was 28.3 weeks, and the median HBV DNA level was 8.0 log10 IU per milliliter. Among 322 deliveries (97% of the participants), there were 319 singleton births, two twin pairs, and one stillborn infant. The median time from birth to administration of hepatitis B immune globulin was 1.3 hours, and the median time from birth to administration of hepatitis B vaccine was 1.2 hours. In the primary analysis, none of the 147 infants (0%; 95% confidence interval [CI], 0 to 2) in the TDF group were infected, as compared with 3 of 147 (2%; 95% CI, 0 to 6) in the placebo group (P=0.12). The rate of adverse events did not differ significantly between groups. The incidence of a maternal alanine aminotransferase level of more than 300 IU per liter after discontinuation of the trial regimen was 6% in the TDF group and 3% in the placebo group (P=0.29). CONCLUSIONS:In a setting in which the rate of mother-to-child HBV transmission was low with the administration of hepatitis B immune globulin and hepatitis B vaccine in infants born to HBeAg-positive mothers, the additional maternal use of TDF did not result in a significantly lower rate of transmission. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT01745822 .).

SUBMITTER: Jourdain G

PROVIDER: S-EPMC5895092 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Tenofovir versus Placebo to Prevent Perinatal Transmission of Hepatitis B.

Jourdain Gonzague G Ngo-Giang-Huong Nicole N Harrison Linda L Decker Luc L Khamduang Woottichai W Tierney Camlin C Salvadori Nicolas N Cressey Tim R TR Sirirungsi Wasna W Achalapong Jullapong J Yuthavisuthi Prapap P Kanjanavikai Prateep P Na Ayudhaya Orada P OP Siriwachirachai Thitiporn T Prommas Sinart S Sabsanong Prapan P Limtrakul Aram A Varadisai Supang S Putiyanun Chaiwat C Suriyachai Pornnapa P Liampongsabuddhi Prateung P Sangsawang Suraphan S Matanasarawut Wanmanee W Buranabanjasatean Sudanee S Puernngooluerm Pichit P Bowonwatanuwong Chureeratana C Puthanakit Thanyawee T Klinbuayaem Virat V Thongsawat Satawat S Thanprasertsuk Sombat S Siberry George K GK Watts Diane H DH Chakhtoura Nahida N Murphy Trudy V TV Nelson Noele P NP Chung Raymond T RT Pol Stanislas S Chotivanich Nantasak N

The New England journal of medicine 20180301 10

<h4>Background</h4>Pregnant women with an elevated viral load of hepatitis B virus (HBV) have a risk of transmitting infection to their infants, despite the infants' receiving hepatitis B immune globulin.<h4>Methods</h4>In this multicenter, double-blind clinical trial performed in Thailand, we randomly assigned hepatitis B e antigen (HBeAg)-positive pregnant women with an alanine aminotransferase level of 60 IU or less per liter to receive tenofovir disoproxil fumarate (TDF) or placebo from 28 w ...[more]

PMID: 29514030

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Project description:Background. Hepatitis B virus (HBV) infections are perinatally transmitted from chronically infected mothers. Supplemental antiviral therapy during late pregnancy with lamivudine (LAM), telbivudine (LdT), or tenofovir (TDF) can substantially reduce perinatal HBV transmission compared to postnatal immunoprophylaxis (IP) alone. However, the cost-effectiveness of these measures is not clear. Aim. This study evaluated the cost-effectiveness from a societal perspective of supplemental antiviral agents for preventing perinatal HBV transmission in mothers with high viral load (>6 log10 copies/mL). Methods. A systematic review and network meta-analysis were performed for the risk of perinatal HBV transmission with antiviral therapies. A decision analysis was conducted to evaluate the clinical and economic outcomes in China of four competing strategies: postnatal IP alone (strategy IP), or in combination with perinatal LAM (strategy LAM + IP), LdT (strategy LdT + IP), or TDF (strategy TDF + IP). Antiviral treatments were administered from week 28 of gestation to 4 weeks after birth. Outcomes included treatment-related costs, number of infections, and quality-adjusted life years (QALYs). One- and two-way sensitivity analyses were performed to identify influential clinical and cost-related variables. Probabilistic sensitivity analyses were used to estimate the probabilities of being cost-effective for each strategy. Results. LdT + IP and TDF + IP averted the most infections and HBV-related deaths, and gained the most QALYs. IP and TDF + IP were dominated as they resulted in less or equal QALYs with higher associated costs. LdT + IP had an incremental $2,891 per QALY gained (95% CI [$932-$20,372]) compared to LAM + IP (GDP per capita for China in 2013 was $6,800). One-way sensitivity analyses showed that the cost-effectiveness of LdT + IP was only sensitive to the relative risk of HBV transmission comparing LdT + IP with LAM + IP. Probabilistic sensitivity analyses demonstrated that LdT + IP was cost-effective in most cases across willingness-to-pay range of $6,800 ∼ $20,400 per QALY gained. Conclusions. For pregnant HBV-infected women with high levels of viremia, supplemental use of LdT during late pregnancy combined with postnatal IP for infants is cost-effective in China.

Project description:To evaluate maternal hepatitis B virus (HBV) DNA as risk for perinatal HBV infection among infants of HBV-infected women in California.Retrospective analysis among infants born to hepatitis B surface antigen (HBsAg)-positive mothers who received post vaccination serologic testing (PVST) between 2005 and 2011 in California. Demographic information was collected from the California Department of Public Health Perinatal Hepatitis B Program databaseand matched to birth certificate records. HBV DNA level and hepatitis B e antigen (HBeAg) status were obtained from three large commercial laboratories in California and provider records if available and matched to mother infant pairs. Univariate analysis compared infected and uninfected infants. Multivariate analysis was restricted to infected infants and controls with complete maternal HBV DNA results using a predefined high HBV DNA level of > 2 × 107 IU/mL, a 5:1 ratio of cases to controls and a two-sided confidence level of 95%.A total of 17687 infants were born to HBsAg positive mothers in California between Jan 1 2005 and Dec 31, 2011. Among 11473 infants with PVST, only 125 (1.1%) were found to be HBV infected. Among these infected infants, lapses in Advisory Committee on Immunization Practices recommended post exposure prophylaxis (PEP) occurred in only 9 infants. However, PEP errors were not significantly different between infected and uninfected infants. Among the 347 uninfected and infected infants who had maternal HBeAg and HBV DNA level, case-control analysis found HBeAg positivity (70.4% vs 28.9%, OR = 46.76, 95%CI: 6.05-361.32, P < 0.001) and a maternal HBV DNA level ≥ 2 × 107 IU/mL (92.6% vs 18.5%, OR = 54.5, 95%CI: 12.22-247.55, P < 0.001) were associated with perinatal HBV infection. In multivariate logistic regression, maternal HBV DNA level ≥ 2 × 107 IU/mL was the only significant independent predictor of perinatal HBV infection.In California, transmission is low and most infected infants receive appropriate PEP and vaccination. Maternal HBV DNA ≥ 2 × 107 IU/mL is associated with high risk of perinatal infection.

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Tenofovir versus Placebo to Prevent Perinatal Transmission of Hepatitis B.

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Tenofovir versus Placebo to Prevent Perinatal Transmission of Hepatitis B.

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